Publications by authors named "Ying Lu"

1,384 Publications

  • Page 1 of 1

Identification of flexible Pif1-DNA interactions and their impacts on enzymatic activities.

Nucleic Acids Res 2022 Jun 24. Epub 2022 Jun 24.

Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Flexible regions in biomolecular complexes, although crucial to understanding structure-function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structure determination methods. Taking two Pif1 helicases (ScPif1 and BsPif1) as model systems, we found that, besides a few tightly bound nucleotides, adjacent solvent-exposed nucleotides interact dynamically with the helicase surfaces. The whole nucleotide segment possessed curved conformations and covered the two RecA-like domains of the helicases, which are essential for the inch-worm mechanism. The synergetic approach reveals that the interactions between the exposed nucleotides and the helicases could be reduced by large stretching forces or electrostatically shielded with high-concentration salt, subsequently resulting in reduced translocation rates of the helicases. The dynamic interactions between the exposed nucleotides and the helicases underlay the force- and salt-dependences of their enzymatic activities. The present single-molecule based approach complements high-resolution structural methods in deciphering the molecular mechanisms of the helicases.
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http://dx.doi.org/10.1093/nar/gkac529DOI Listing
June 2022

Lactobacillus plantarum supplementation alleviates liver and intestinal injury in parenteral nutrition-fed piglets.

JPEN J Parenter Enteral Nutr 2022 Jun 22. Epub 2022 Jun 22.

Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: Long-term parenteral nutrition (PN) causes parenteral nutrition-associated liver disease (PNALD) for which therapeutic approaches are limited. This study aimed to investigate the effects of Lactobacillus plantarum CGMCC 1258 (LP) on liver and intestinal injury in the PN-fed neonatal piglets.

Methods: The piglets received PN with or without oral LP for 14 days. The levels of liver enzymes and inflammatory markers were measured using biochemical kits and q-RT-PCR. Serum fibroblast growth factor 19 (FGF19) was detected using an enzyme-linked immunosorbent assay (ELISA). The bile acid profiles in the liver, serum, and intestinal contents were determined using ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). The composition of intestinal bacteria was analyzed with 16S rRNA gene amplicon sequencing.

Results: LP supplementation was associated with improved markers of liver disease, inflammation, and oxidative stress in PN-fed piglets. Moreover, markers of intestinal injury and inflammation were alleviated by LP in PN-fed piglets. Mechanistically, LP increased the abundance of Lactobacillus in ileal contents and stimulated FGF19 expression in ileal mucosa. Subsequently, it increased the expression of small heterodimer partner (SHP) and inhibited cholesterol 7α-hydroxylase (CYP7A1) expression in the liver. Additionally, LP altered the systemic composition and metabolism of bile acids.

Conclusions: LP alleviated liver and intestinal injury in PN-fed neonatal piglets by altering the composition of intestinal bacteria and bile acids. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jpen.2429DOI Listing
June 2022

An electrochemical aptasensor with N protein binding aptamer-complementary oligonucleotide as probe for ultra-sensitive detection of COVID-19.

Biosens Bioelectron 2022 Jun 8;213:114436. Epub 2022 Jun 8.

Department of Applied Chemistry, Key Laboratory of Agricultural Sensors, Ministry of Agriculture and Rural Affairs, Anhui Agricultural University, Hefei, 230036, PR China. Electronic address:

The emergence of the COVID-19 epidemic has affected the lives of hundreds of millions of people globally. There is no doubt that the development of fast and sensitive detection methods is crucial while the worldwide effective vaccination programs are miles away from actualization. In this study, we have reported an electrochemical N protein aptamer sensor with complementary oligonucleotide as probe for the specific detection of COVID-19. The electrochemical aptasensor was prepared by fixing the double-stranded DNA hybrid obtained by the hybridization of N protein aptamer and its Fc-labeled complementary strand on the surface of a gold electrode. After incubation with the target, the aptamer dissociated from the labeled complementary DNA oligonucleotide hybrid to preferentially bind with N protein in the solution. The concentration of N protein was measured by detecting the changes in electrochemical current signals induced by the conformational transformation of the complementary DNA oligonucleotide left on the electrode surface. The sensor had a linear relationship between the logarithm of the N protein concentration from 10 fM to 100 nM (ΔI = 0.098 log C/fM - 0.08433, R = 0.99), and the detection limitation was 1 fM (S/N = 3). The electrochemical aptamer sensor was applied to test the spiked concentrations of throat swabs and blood samples from three volunteers, and the obtained results proved that the sensor has great potentials for the early detection of COVID-19 in patients.
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http://dx.doi.org/10.1016/j.bios.2022.114436DOI Listing
June 2022

Extensions of empirical likelihood and chi-squared-based tests for ordered alternatives.

J Appl Stat 2022 23;49(1):24-43. Epub 2020 Jul 23.

Department of Statistics and Operational Research, Universidad Complutense de Madrid, Madrid, Spain.

Several methods for comparing populations have been proposed in the literature. These methods assess the same null hypothesis of equal distributions but differ in the alternative hypothesis they consider. We focus on two important alternative hypotheses: monotone and umbrella ordering. Two new families of test statistics are proposed, including two known tests, as well as two new powerful tests under monotone ordering. Furthermore, these families are adapted for testing umbrella ordering. We compare some members of the families with respect to power and Type I errors under different simulation scenarios. Finally, the methods are illustrated in several applications to real data.
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http://dx.doi.org/10.1080/02664763.2020.1796944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041694PMC
July 2020

PanaxGDB: A Comprehensive Platform for .

Front Plant Sci 2022 25;13:883818. Epub 2022 May 25.

State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan, The Key Laboratory of Medicinal Plant Biology of Yunnan Province, National & Local Joint Engineering Research Center on Germplasms Innovation & Utilization of Chinese Medicinal Materials in Southwest China, Yunnan Agricultural University, Kunming, China.

The genus is a valuable natural medicinal source used worldwide that contains high levels of triterpenoid saponins with extensive pharmacological activities. In past decades, molecular biotechnology and breeding techniques have been respectively used to generate omics data and information on cultivars primarily from (ginseng), (American ginseng), and (Sanqi) to biosynthesize valuable saponins, improve product quality, and conduct cost-controlled cultivation. Although much data have been produced, there are concerns that redundant data might be generated and that relatively scattered data might be overlooked. Therefore, many scientists desire a reliable, comprehensive omics database of the genus that could save time and promote integrated analysis. Therefore, to provide all-inclusive, reliable, and valuable information on the genus, PanaxGDB, an open comprehensive database that integrates data on omics and information on varieties, was established. The database contains information on nearly 600 compounds from 12 species, draft genomic sequences with annotations and gene expression levels, single nucleotide polymorphisms, genome-wide association analysis based on agronomic traits, globally collected germplasm information, summaries, omics data of the genus, and online versatile analytic tools. The genus database will be updated when new data are released to continue serving as a central portal to boost research on the biology and functions of . PanaxGDB is available at: http://panaxGDB.ynau.edu.cn.
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http://dx.doi.org/10.3389/fpls.2022.883818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174995PMC
May 2022

Prevalence and genetic diversity of in pet dogs from Zhengzhou, central China and the association between gut microbiota and fecal characteristics during infection.

One Health 2022 Jun 20;14:100401. Epub 2022 May 20.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, People's Republic of China.

As a common zoonotic intestinal parasite, could infect humans and various mammals worldwide, including pet dogs, leading to giardiasis. This study detected the infection of in asymptomatic pet dogs in Zhengzhou, and evaluated the possibility of zoonosis and the relationship between gut microbiota and fecal characteristics. We randomly collected 448 fresh fecal samples from Zhengzhou, and was screened based on the beta-giardin (), glutamate dehydrogenase (), and triose phosphate isomerase () genes. The difference of gut microbiota between five s-positive and five -negative samples was investigated by 16S rRNA gene sequencing. The overall prevalence of was 7.1% (32/448) based on , , and locus, two assemblages (C = 13, D = 14) and five (15.6%) mixed infection (C + D) were identified. Moreover, compared with the -negative group, the diversity of gut microbiota increased in -positive group. The decrease of spp. and considerable increase of spp. were associated with the fecal characteristics. These results show that the transmission of zoonotic giardiasis between humans and pet dogs is rare in Zhengzhou, central China, and support the use of spp. as a potential probiotic agent to improve intestinal health in dogs, or even humans, by treating s. Therefore, the public health significance of to humans, companion animals, and the environment should be further evaluated from One Health perspective.
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http://dx.doi.org/10.1016/j.onehlt.2022.100401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171527PMC
June 2022

Effect of Combining Conventional and Telehealth Methods on Managing Peritoneal Dialysis Patients: A Retrospective Single-Center Study.

Int J Clin Pract 2022 3;2022:6524717. Epub 2022 Mar 3.

Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China.

Objective: This study aimed to explore follow-up mode changes for peritoneal dialysis (PD) patients and their effects on PD quality during the COVID-19 pandemic.

Methods: A retrospective single-center study was conducted. All patients who received PD treatment at the Second Affiliated Hospital of Soochow University between January 2018 and March 2020 were enrolled in this study. Patient data during the first quarter of 2018 (Q1-2018), the first quarter of 2019 (Q1-2019), and the first quarter of 2020 (Q1-2020) were collected.

Results: No significant differences were observed for any serum examinations in different follow-up periods ( > 0.05). A significantly reduced outpatient follow-up rate was observed in Q1-2020 compared with Q1-2018 and Q1-2019 (71.6% Vs 78.9% Vs 84.7%, < 0.001), accompanied by a significantly increased remote follow-up rate (28.4% Vs 21.1% Vs 15.3%, < 0.001). Compared with Q1-2018 and Q1-2019, the hospitalization rate (27.7% Vs 30.9% Vs 15.7%, < 0.001) and the incidence of peritonitis (0.162 Vs 0.186 Vs 0.08 per patient-year, < 0.001) decreased significantly in Q1-2020. PD patients had a significant decline in the drop-out rate for Q1-2020 compared with Q1-2019 (4.4% Vs 7.3% Vs 2.2%, < 0.001). No differences in the incidence of catheter-related infections were observed. No significant differences were observed for any peritoneal dialysis key performance indicators (KPIs) between outpatient follow-up and remote follow-up patients.

Conclusion: During the COVID-19 pandemic (Q1-2020), our center practiced more remote follow-up procedures in PD patients. The hospitalization rate and peritonitis incidence were significantly decreased compared with the same time in previous years. No statistical differences were observed in other KPIs for peritoneal dialysis. This study shows that telehealth methods are a reasonable alternative to in-person care in the care/management of PD patients.
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http://dx.doi.org/10.1155/2022/6524717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159208PMC
June 2022

Association of Epstein-Barr virus DNA and SAA with S1 maintenance therapy outcomes in patients with metastatic nasopharyngeal carcinoma.

Future Oncol 2022 Jun 9. Epub 2022 Jun 9.

Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, 545000, China.

The relevant biomarkers in predicting maintenance therapy (MT) outcomes in metastatic nasopharyngeal carcinoma (NPC) are yet unclear. Metastatic NPC patients were randomly divided into MT (S1-MT) and non-MT groups. The association of Epstein-Barr virus DNA (EBV-DNA) and SAA with survival was assessed. A total of 183 patients were included. S1-MT significantly increased the progression-free survival (PFS) and overall survival (OS) of the metastatic NPC patients (both p < 0.001). For patients who were EBV-DNA positive or had decreased SAA, the PFS and OS increased significantly after S1-MT (both p < 0.001), while patients with stable SAA did not benefit from S1-MT. S1-MT improved the PFS and OS of metastatic NPC patients. EBV-DNA and SAA status were closely associated with the outcomes of S1-MT. ChiCTR-IOR-16007939.
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http://dx.doi.org/10.2217/fon-2022-0010DOI Listing
June 2022

HERC5/IFI16/p53 signaling mediates breast cancer cell proliferation and migration.

Life Sci 2022 Aug 4;303:120692. Epub 2022 Jun 4.

College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address:

Aims: This study aims to find differentially expressed ubiquitination-related gene(s) and elucidates their biological significance in breast cancer.

Main Methods: Differentially expressed genes were profiled in MCF-7 and MDA-MB-231 cells by using PCR array method. Abnormal expression of HERC5 was studied in the cells and in breast cancer specimens via Quantitative Real-time PCR and western blot. Cell proliferation and cell migration abilities were evaluated by using cell counting kits, or through colony formation, wound healing and trans-well assays. HERC5 target proteins were investigated via proteomic, co-immunoprecipitation and western blot methods. Down-stream signaling pathways were investigated through gene expression/knockdown methods.

Key Findings: Huge increase of HERC5 expression was found in MCF-7 and MDA-MB-231 cells, knockdown of which repressed the cell proliferation and migration. HERC5 interacted with IFI16, mediated IFI16 ISGylation at K274 and facilitated IFI16 proteasomal degradation. IFI16 acted as a tumor suppressor and to some extent mediated the HERC5 function in the breast cancer (BC) cells. HERC5 was negatively correlated with IFI16 protein, while IFI16 was positively correlated to p53 expression at mRNA and protein levels, which indicates a novel signaling pathway - HERC5/IFI16/p53. HERC5 expression was increased in glucose-starved BC cells and in human breast cancer tissues, accompanied with the decrease of IFI16 and P53.

Significance: Our work reveals the abnormal expression of HERC5 and its carcinogenic role in breast cancer cells, which is probably mediated by an HERC5/IFI16/p53 signaling pathway. This work also provides potential diagnostic/therapeutic biomarkers for breast cancer diagnosis and treatment.
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http://dx.doi.org/10.1016/j.lfs.2022.120692DOI Listing
August 2022

Clinical Characteristics and Outcome Analysis for HLA Loss Patients Following Partially Mismatched Related Donor Transplantation Using HLA Chimerism for Loss of Heterozygosity Analysis by Next-Generation Sequencing.

Cell Transplant 2022 Jan-Dec;31:9636897221102902

Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Genomic loss of mismatched human leukocyte antigen (HLA loss) is one of the most vital immune escape mechanisms of leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the methods currently used for HLA loss analysis have some shortcomings. Limited literature has been published, especially in lymphoid malignancies. This study aims to evaluate the incidences, risk factors of HLA loss, and clinical outcomes of HLA loss patients. In all, 160 patients undergoing partially mismatched related donor (MMRD) transplantation from 18 centers in China were selected for HLA loss analysis with the next-generation sequencing (NGS)-based method, which was validated by HLA-KMR. Variables of the prognostic risk factors for HLA loss or HLA loss-related relapse were identified with the logistic regression or the Fine and Gray regression model. An HLA loss detection system, HLA-CLN [HLA chimerism for loss of heterozygosity (LOH) analysis by NGS], was successfully developed. Forty (25.0%) patients with HLA loss were reported, including 27 with myeloid and 13 with lymphoid malignancies. Surprisingly, 6 of those 40 patients did not relapse. The 2-year cumulative incidences of HLA loss (22.7% vs 22.0%, = 0.731) and HLA loss-related relapse (18.4% vs 20.0%, = 0.616) were similar between patients with myeloid and lymphoid malignancies. The number of HLA mismatches (5/10 vs <5/10) was significantly associated with HLA loss in the whole cohort [odds ratio (OR): 3.15, = 0.021] and patients with myeloid malignancies (OR: 3.94, = 0.021). A higher refined-disease risk index (OR: 6.91, = 0.033) and donor-recipient ABO incompatibility (OR: 4.58, = 0.057) contributed to HLA loss in lymphoid malignancies. To sum up, HLA-CLN could overcome the limitations of HLA-KMR and achieve a better HLA coverage for more patients. The clinical characteristics and outcomes were similar in patients with HLA loss between myeloid and lymphoid malignancies. In addition, the results suggested that a patient with HLA loss might not always relapse.
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http://dx.doi.org/10.1177/09636897221102902DOI Listing
June 2022

The truncated form of flagellin (tFlic) provides the 2dCap subunit vaccine with better immunogenicity and protective effects in mice.

Anim Dis 2022 2;2(1):11. Epub 2022 Jun 2.

Department of Veterinary Medicine, Institute of Preventive Veterinary Medicine & Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, 866 Yuhangtang road, Hangzhou, 310058 China.

Porcine circovirus type 2 (PCV2) is the main causative agent of porcine circovirus-associated diseases, and it causes substantial economic losses in the swine industry each year. It is crucial to develop an effective vaccine against the circulating strain PCV2d, which is prone to substantial degrees of mutation. In this study, a truncated form of flagellin (tFlic: 85-111 aa) was inserted into the C-terminal sequence of 2dCap, and Western blotting results showed that recombinant Cap-tFlic VLPs were successfully expressed. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) data indicated that purified recombinant Cap-tFlic fusion proteins existed in the form of polymers and that tFlic could not affect the formation and internalization of VLPs. Integrated Cap-tFlic VLPs induced the expression of antigen presentation-related factors (MHC-II and CD86) by bone marrow-derived dendritic cells (BM-DCs), and the expression of TLR5-related factors (TNF-α) was dramatically elevated. Mice intramuscularly immunized with Cap-tFlic VLPs exhibited significantly higher levels of Cap-specific antibodies and neutralizing antibodies than mice immunized with wild-type Cap VLPs. The data obtained in the current study indicate that Cap-tFlic may be a candidate for a subunit vaccine against PCV2 in the future.
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http://dx.doi.org/10.1186/s44149-022-00043-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160859PMC
June 2022

Multiple-day administration of fosaprepitant combined with tropisetron and olanzapine improves the prevention of nausea and vomiting in patients receiving chemotherapy prior to autologous hematopoietic stem cell transplant: a retrospective study.

Ann Hematol 2022 Jun 6. Epub 2022 Jun 6.

Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, 315101, China.

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.
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http://dx.doi.org/10.1007/s00277-022-04877-wDOI Listing
June 2022

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation.

World J Clin Cases 2022 May;10(14):4425-4435

Institute of Hematology Research, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hang Zhou 310006, Zhejiang Province, China.

Background: With the rapid development of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), primary poor graft function (PGF) has become a life-threatening complication. Effective therapies for PGF are inconclusive. New Chinese patent medicine Pai-Neng-Da (PND) Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity. Still, the application of PND capsule in hematopoietic stem cell transplantation, especially in the haplo-HSCT setting, has not yet been reported.

Aim: To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.

Methods: We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People's Hospital of Ningbo University between April 1, 2015 and June 30, 2020. Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group. In addition, 31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group. Subsequently, we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores, and the survival between the PND group and the non-PND group, using the chi-square test, Fisher's exact test, and the Kaplan-Meier method.

Results: The duration of platelet engraftment was shorter in the PND group than in the non-PND group ( = 0.039). The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group ( = 0.033 and = 0.035, respectively). In addition, PND capsule marginally reduced the rate of PGF ( = 0.027) and relapse ( = 0.043). After 33 (range, 4-106) months of follow-up, the 3-year relapse-free survival ( = 0.046) and progression-free survival ( = 0.049) were improved in the PND group than in the non-PND group. Also, the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group ( = 0.022). Moreover, the adverse events caused by PND capsule were mild. Nevertheless, there were no significant differences in the duration of neutrophil engraftment, the risk of infection within 100 days after haplo-HSCT, the acute graft-versus-host disease, or the 3-year overall survival between the two groups.

Conclusion: PND capsule could promote hematopoiesis reconstitution, improve the therapeutic efficacy of Chinese medical symptom scores, present anti-tumor effectiveness, and prolong the survival of acute leukemia patients with haplo-HSCT.
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http://dx.doi.org/10.12998/wjcc.v10.i14.4425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125279PMC
May 2022

Highly Enforced Rate Capability of a Graphite Anode via Interphase Chemistry Tailoring Based on an Electrolyte Additive.

J Phys Chem Lett 2022 Jun 5:5151-5159. Epub 2022 Jun 5.

School of Chemistry, South China Normal University, Guangzhou 510006, China.

The rate capability of lithium-ion batteries is highly dependent on the interphase chemistry of graphite anodes. Herein, we demonstrate an anode interphase tailoring based on a novel electrolyte additive, lithium dodecyl sulfate (LiDS), which greatly improves the rate capability and cyclic stability of graphite anodes. Upon application of 1% LiDS in a base electrolyte, the discharge capacity at 2 C is improved from 102 to 240 mAh g and its capacity retention is enhanced from 51% to 94% after 200 cycles at 0.5 C. These excellent performances are attributed to the preferential absorption of LiDS and the as-constructed interphase chemistry that is mainly composed of organic long-chain polyether and inorganic lithium sulfite. The long-chain polyether possesses flexibility endowing the interphase with robustness, while its combination with inorganic lithium sulfite accelerates lithium intercalation/deintercalation kinetics via decreasing the resistance for charge transfer.
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http://dx.doi.org/10.1021/acs.jpclett.2c01183DOI Listing
June 2022

Utilization of anti-tumor necrosis factor biologics in Very Early Onset Inflammatory Bowel Disease (VEOIBD): a multicenter retrospective cohort study from North America.

J Pediatr Gastroenterol Nutr 2022 May 27. Epub 2022 May 27.

University of North Carolina in Chapel Hill, Chapel Hill, NC, United States.

Background: Research on the utilization and effectiveness of anti-TNF biologics in children with Very Early Onset Inflammatory Bowel (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort.

Methods: We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification and presence of combined immunomodulatory treatment vs. monotherapy.

Results: Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [ 50% Crohn's disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years and 45% at 5 years from diagnosis; 56 (55%) were treated between 0-6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (HR 0.17; 95% CI, 0.06-0.51; p=0.001).

Conclusions: Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable to older children. Having Crohn's disease (compared to UC/IBD-U) is associated with greater durability.An infographic is available for this article at: http://links.lww.com/MPG/C788.
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http://dx.doi.org/10.1097/MPG.0000000000003464DOI Listing
May 2022

Topical Simvastatin Improves Lesions of Diffuse Normolipemic Plane Xanthoma by Inhibiting Foam Cell Pyroptosis.

Front Immunol 2022 10;13:865704. Epub 2022 May 10.

Department of Dermatology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Xanthoma pathogenesis is speculated to be associated with oxidized low-density lipoprotein (ox-LDL) deposition, although this remains unclear. Most patients with diffuse plane xanthomas present elevated blood lipid levels, and they benefit from treatment with oral lipid-lowering agents. However, there is no available treatment for diffuse normolipemic plane xanthoma (DNPX). In this study, for the first time, we used a topical simvastatin ointment to treat DNPX in three pediatric patients and observed favorable results. Immunofluorescence staining showed that the pyroptotic pathway was significantly attenuated after topical simvastatin application on the skin lesions of the patients. As ox-LDL deposition was observed in the lesions, we used ox-LDL to build a foam cell model . In the ox-LDL-induced foam cell formation, simvastatin consistently inhibited pyroptotic activation and inflammation in the macrophages. Additionally, the overexpression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), the known target of statins, reversed the effects of simvastatin. Moreover, gasdermin D (GSDMD) or HMGCR knockdown inhibited ox-LDL-induced pyroptosis. Furthermore, the immunoprecipitation results confirmed the interaction between NLRP3 and HMGCR, and this interaction was inhibited by simvastatin. In conclusion, we demonstrated that topical application of simvastatin ointment might be a promising treatment for DNPX skin lesions and that this therapeutic effect may be related to pyroptosis inhibition HMGCR inhibition in foam cells. Moreover, xanthoma pathogenesis might be associated with ox-LDL deposition and inflammation.
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http://dx.doi.org/10.3389/fimmu.2022.865704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128406PMC
May 2022

Europe vs. China: (Araneae, Pholcidae) from Yanshan-Taihang Mountains confirms uneven distribution of spiders in Eurasia.

Zool Res 2022 Jul;43(4):532-534

College of Life Science, Shenyang Normal University, Shenyang, Liaoning 110034, China.

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http://dx.doi.org/10.24272/j.issn.2095-8137.2022.103DOI Listing
July 2022

Comparing the effectiveness of secondary distribution of HIV/syphilis dual self-testing to testing card referral in promoting HIV testing among gay, bisexual, and other men who have sex with men in Guangzhou, China: a quasi-experimental study.

Sex Health 2022 May 26. Epub 2022 May 26.

Background: Social network approaches to testing allow individuals (indexes) to distribute tests to social networks (alters). This quasi-experimental study compared two social network-based testing strategies in promoting human immunodeficiency virus (HIV) testing among Chinese gay, bisexual, and other men who have sex with men (GBMSM).

Methods: GBMSM aged ≥18years were recruited from Guangzhou, China. From May to September 2019, indexes could distribute blood-based HIV/syphilis dual self-testing kits to people within their social network. Indexes recruited from October 2019 to January 2020 could send HIV testing cards to their social networks for free facility-based tests. Alters were encouraged to upload a photo verification of test results. Indexes and alters received incentives during both periods.

Results: There were 245 participants who were assessed for eligibility and 208/245 (84.9%) were eligible. 106 and 102 indexes were recruited in the secondary distribution and testing card arms respectively. 154/208 (74.0%) completed follow up at 1 month. 92 indexes in the secondary distribution arm self-reported distributions to 179 unique alters, and 62 in the testing card arm to 26 unique alters. An average of 1.95 (standard deviation [s.d.]=1.90) HIV/syphilis dual self-tests and 0.42 (s.d.=0.78) HIV testing cards were distributed, generating a risk difference of 1.53 (95% confidence interval [CI] 1.09, 1.96). Indexes self-identifying as gay (P=0.007) or having previously tested (P=0.02) distributed more tests. Secondary distribution cost less per alter tested (USD120 vs USD9408).

Conclusions: Secondary distribution engaged more GBMSM to distribute tests and reached more GBMSM to test compared to referral cards, suggesting advantage in facilitating testing uptake among Chinese GBMSM.
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http://dx.doi.org/10.1071/SH21176DOI Listing
May 2022

Mptx2 defends against peritoneal infection by methicillin-resistant staphylococcus aureus.

Int Immunopharmacol 2022 Jul 21;108:108856. Epub 2022 May 21.

Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Methicillin-resistant Staphylococcus aureus (MRSA) has an increasing prevalence of multi-drug resistance. There is an urgent need for developing novel approaches to combat MRSA infection. Mucosal pentraxin 2 (Mptx2) is predicted to be a member of the pentraxin family, but its biological function is still unknown. This study is aimed to explore the roles of Mptx2 in MRSA-associated peritoneal infection. The recombinant Mptx2 protein is used to evaluate its antibacterial activity. Biofilm formation assay and macrophage phagocytic experiment are performed to explore the involved mechanisms. The effects of Mptx2 on peritoneal infection are investigated in a MRSA-induced peritoneal infected model. We here show that addition of Mptx2 suppresses the growth and biofilm formation of MRSA in vitro. Enzyme-linked immunosorbent assay (ELISA) binding analysis shows that Mptx2 protein directly binds to the MRSA. Additionally, Mptx2 supplementation promotes macrophages to phagocytize and clear the MRSA. In the MRSA-infected peritonitis model, Mptx2 administration reduces MRSA loading in peritoneal organs and alleviates peritoneal damage. Mptx2 knockout aggravates MRSA infection-induced peritoneal injury. In conclusion, our findings reveal that Mptx2 has bactericidal activity against MRSA both in vitro and in vivo, which may shed light on the discovery and development of novel strategies for MRSA-infected peritonitis.
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http://dx.doi.org/10.1016/j.intimp.2022.108856DOI Listing
July 2022

Non-oxidative pentose phosphate pathway controls regulatory T cell function by integrating metabolism and epigenetics.

Nat Metab 2022 May 23;4(5):559-574. Epub 2022 May 23.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Regulatory T (T) cells are critical for maintaining immune homeostasis and preventing autoimmunity. Here, we show that the non-oxidative pentose phosphate pathway (PPP) regulates T function to prevent autoimmunity. Deletion of transketolase (TKT), an indispensable enzyme of non-oxidative PPP, in T cells causes a fatal autoimmune disease in mice, with impaired T suppressive capability despite regular T numbers and normal Foxp3 expression levels. Mechanistically, reduced glycolysis and enhanced oxidative stress induced by TKT deficiency triggers excessive fatty acid and amino acid catabolism, resulting in uncontrolled oxidative phosphorylation and impaired mitochondrial fitness. Reduced α-KG levels as a result of reductive TCA cycle activity leads to DNA hypermethylation, thereby limiting functional gene expression and suppressive activity of TKT-deficient T cells. We also find that TKT levels are frequently downregulated in T cells of people with autoimmune disorders. Our study identifies the non-oxidative PPP as an integrator of metabolic and epigenetic processes that control T function.
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http://dx.doi.org/10.1038/s42255-022-00575-zDOI Listing
May 2022

Sensitive and Rapid Diagnosis of Respiratory Virus Coinfection Using a Microfluidic Chip-Powered CRISPR/Cas12a System.

Small 2022 May 22:e2200854. Epub 2022 May 22.

State Key Laboratory of Membrane Biology, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, China.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 is profoundly influencing the global healthcare system and people's daily lives. The high resource consumption of coronavirus disease 2019 (COVID-19) is resulting in insufficient surveillance of coinfection or resurgence of other critical respiratory epidemics, which is of public concern. To facilitate evaluation of the current coinfection situation, a microfluidic system (MAPnavi) is developed for the rapid (<40 min) and sensitive diagnosis of multiple respiratory viruses from swab samples in a fully sealed and automated manner, in which a nested-recombinase polymerase amplification and the CRISPR-based amplification system is first proposed to ensure the sensitivity and specificity. This novel system has a remarkably low limit of detection (50-200 copies mL ) and is successfully applied to detect 171 clinical samples (98.5% positive predictive agreement; 100% negative predictive agreement), and the results identify 45.6% coinfection among clinical samples from patients with COVID-19. This approach has the potential to shift diagnostic and surveillance efforts from targeted testing for a high-priority virus to comprehensive testing of multiple virus sets and to greatly benefit the implementation of decentralized testing.
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http://dx.doi.org/10.1002/smll.202200854DOI Listing
May 2022

Patchouli alcohol protects against myocardial ischaemia-reperfusion injury by regulating the Notch1/Hes1 pathway.

Pharm Biol 2022 Dec;60(1):949-957

Electrocardiogram room of Department of Functional Examination, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Context: Patchouli alcohol (PA) has protective effects on cerebral ischaemia/reperfusion (I/R) injury, but its efficacy on myocardial ischaemia-reperfusion (MI/R) has yet to be addressed.

Objective: To examine the therapeutic effect of PA on myocardial ischaemia-reperfusion (I/R) injury.

Materials And Methods: C57BL/6 male mice were randomly divided into sham, MI/R, MI/R + PA-10, MI/R + PA-20 and MI/R + PA-40 groups. MI/R model was established by ligating the anterior descending coronary artery of the heart. stimulated IR cell model was constructed by using the rat cardiomyocyte H9C2 cell line. Mice in the treatment groups were intraperitoneally injected with PA (10, 20, 40 mg/kg) for 30 days then subjected to surgery, and cells in the experimental group were pre-treated with PA (1, 10 or 100 μmol/L). After treatment, mouse heart function, myocardial injury markers, myocardial infarction and Notch1/Hes1 expression, endoplasmic reticulum stress markers, and apoptosis-related proteins were determined.

Results: , PA treatment improved hemodynamic parameter changes and myocardial enzymes, increased the left ventricular ejection fraction and left ventricular fractional shortening, reduced the left ventricular end-systolic diameter and inhibited CK-MB, cTnI and cTnT levels. In addition, PA attenuated myocardial tissue damage and apoptosis. PA treatment elevated Notch1, NICD and Hes1 levels and suppressed the levels of ATF4, p-PERK/PERK, and cleaved caspase-3/caspase-3 and .

Discussion And Conclusion: PA protects against MI/R, possibly by modulating ER stress, apoptosis and the Notch1/Hes1 signalling pathways. These findings indicate that PA may be a promising candidate for treating ischaemic heart diseases.
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http://dx.doi.org/10.1080/13880209.2022.2064881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122376PMC
December 2022

Serum Atrial Natriuretic Peptide, Promoter Methylation, and Cardiovascular Disease: A 10-year Follow-Up Study in Chinese Adults.

Glob Heart 2022 7;17(1):27. Epub 2022 Apr 7.

Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.

Background: Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population.

Methods: Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene () promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and promoter methylation with incident CVD.

Results: During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03-1.44, = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30-0.82, = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at promoter as a whole was significantly associated with incident CVD ( < 0.05).

Conclusions: Increased proANP and hypomethylation at promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the gene may participate in the mechanisms of CVD.
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http://dx.doi.org/10.5334/gh.1116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992767PMC
May 2022

Discovery of 4-methoxy-N-(1-naphthyl)benzenesulfonamide derivatives as small molecule dual-target inhibitors of tubulin and signal transducer and activator of transcription 3 (STAT3) based on ABT-751.

Bioorg Chem 2022 Aug 10;125:105864. Epub 2022 May 10.

Department of Colorectal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address:

Overexpressed tubulin and continuously activated STAT3 play important roles in the development of many cancers and are potential therapeutic targets. A series of 4-methoxy-N -(1-naphthalene) benzenesulfonamide derivatives were designed and optimized based on β-tubulin inhibitor ABT-751 to verify whether STAT3 and tubulin dual target inhibitors have better antitumor effects. Compound DL14 showed strong inhibitory activity against A549, MDA-MB-231 and HCT-116 cells in vitro with IC values of 1.35 μM, 2.85 μM and 3.04 μM, respectively. Further experiments showed that DL14 not only competitively bound to colchicine binding site to inhibit tubulin polymerization with IC values 0.83 μM, but also directly bound to STAT3 protein to inhibit STAT3 phosphorylation with IC value of 6.84 μM. Three other compounds (TG03, DL15, and DL16) also inhibit this phosphorylation. In terms of single target inhibition, DL14 is slightly inferior to positive drugs, but it shows a good anti-tumor effect in vivo, and can inhibit >80% of xenograft tumor growth. This study describes a novel 4-methoxy-N-(1-naphthyl) benzenesulfonamide skeleton as an effective double-targeted anticancer agent targeting STAT3 and tubulin.
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http://dx.doi.org/10.1016/j.bioorg.2022.105864DOI Listing
August 2022

Posaconazole oral suspension for secondary antifungal prophylaxis in allogeneic stem cell transplantation recipients: a retrospective study.

BMC Infect Dis 2022 May 15;22(1):465. Epub 2022 May 15.

Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, 315101, China.

Background: There is no consensus on the optimal secondary antifungal prophylaxis (SAP) regimen in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the efficacy and safety of posaconazole oral suspension as secondary prophylaxis of invasive fungal disease (IFD) for allo-HSCT patients.

Methods: We retrospectively reviewed clinical data from prior IFD patients who received posaconazole oral suspension as systemic antifungal prophylaxis between June 2016 and January 2021 and have a follow-up period of 1 year after HSCT. The clinical outcomes of patients with a prior history of IFD (n = 30) and those without (n = 93) were compared.

Results: The 1-year cumulative incidence of prophylaxis failure was 58.3% in the group with prior history of IFD and 41.6% in the group without a prior history of IFD (p = 0.459). The cumulative incidence of proven, probable or possible IFD within 1 year after allo-HSCT was 23.1% in the group with prior history of IFD and 14.1% in the group without prior history of IFD (p = 0.230). There was no significant difference between the cumulative incidence of proven or probable IFD within 1-year after allo-HSCT in the group with a prior history of IFD and the group without (p = 0.807). Multivariate logistic regression revealed cytomegalovirus disease as risk factor for post-transplantation IFD occurrence in posaconazole oral suspension prophylaxis. There was not a significant difference in overall survival between the patients with IFD history and those without (P = 0.559).

Conclusions: Our study support that allo-HSCT recipients with a prior history of IFD and normal GI absorption can choose posaconazole oral suspension as a safe and effective SAP option.
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http://dx.doi.org/10.1186/s12879-022-07442-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107735PMC
May 2022

[Effect of intradermal needling combined with oral motor therapy for salivation in children with cerebral palsy: a randomized controlled trial].

Zhongguo Zhen Jiu 2022 May;42(5):515-9

Department of Child Rehabilitation, Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.

Objective: To compare the effect of combination of intradermal needling with oral motor therapy and simple oral motor therapy on salivation in children with cerebral palsy.

Methods: A total of 60 children with salivation in cerebral palsy were randomized into an observation group and a control group, 30 cases in each group. The observation group was treated with intradermal needling (kept for 24 hours each time at Jiache [ST 6], Dicang [ST 4], tongue three needles, etc. ) and oral motor therapy, while the control group was only given oral motor therapy. The intradermal needling was performed 3 times a week, and oral motor therapy was performed 5 times a week, 4 weeks as a course, totally 3 courses of treatment were required. The classification of teacher drooling scale (TDS), drooling severity and Kubota water swallow test, dysphagia disorders survey (DDS) score were compared before treatment and after 4, 8 and 12 weeks of treatment in both groups, and the clinical efficacy was evaluated.

Results: After 8 weeks of treatment in the observation group and after 12 weeks of treatment in the two groups, the classification of TDS and drooling severity were improved (<0.05), and the observation group was better than the control group after 12 weeks of treatment (<0.05). After 8 and 12 weeks of treatment, the DDS scores of oral period in the observation group were lower than those before treatment (<0.05). The total effective rate in the observation group was 83.3% (25/30), which was higher than 53.3% (16/30) in the control group (<0.05).

Conclusion: The combination of intradermal needling with oral motor therapy can improve salivation symptoms and swallowing function in children with cerebral palsy, the effect is better than oral motor therapy alone, and the effect is earlier.
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http://dx.doi.org/10.13703/j.0255-2930.20210508-0001DOI Listing
May 2022

Self-sampled specimens demonstrate comparable accuracy and consistency to clinician-sampled specimens for HPV detection among men who have sex with men in China.

Sex Transm Infect 2022 May 9. Epub 2022 May 9.

University of North Carolina Project-China, Guangzhou, Guangdong, China

Objectives: Despite a high risk of human papillomavirus (HPV) infection among men who have sex with men (MSM), few have ever tested. This study aimed to evaluate the feasibility and accuracy of HPV self-sampling among Chinese MSM, with the purpose of measuring the feasibility of self-sampling as an alternative in HPV testing scenarios.

Methods: Eligible participants were those who were assigned male at birth, aged 18 or above, had sex with men in the past year and had never gotten HPV vaccine. Participants followed the instructions to self-sample and were also clinician-sampled from the same anatomical sites (oral fluid, penis and rectum) in both approaches. All specimens were processed using multiplex PCR assay. The reference standard of an individual with a true positive for HPV is determined via PCR test, regardless of sampling methods. Sensitivity and specificity were calculated for each approach independently and kappa test was used to assess the consistency between the two approaches.

Results: Overall, 211 MSM were recruited at the local clinic from April to October 2020 in Zhuhai, China. The mean age was 31 years old. Only 3% of the participants sought help from healthcare providers during self-sampling. The prevalence of HPV was 49% (103 of 211). Clinician sampling detected 91 of 103 MSM infected with HPV, with a sensitivity of 88.3% (95% CI 80.2 to 93.6) and a specificity of 100.0% (95% CI 95.7 to 100.0). Self-sampling detected 81 of 103 MSM infected with HPV, with a sensitivity of 78.6% (95% CI 69.2 to 85.9) and a specificity of 100.0% (95% CI 95.7 to 100.0). The level of agreement was moderate between clinician sampling and self-sampling (k=0.67).

Conclusions: Self-sampled HPV testing demonstrated comparable accuracy and consistency to clinician sampling among MSM in China. It holds the potential to complement sexual health services especially among key populations.
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http://dx.doi.org/10.1136/sextrans-2022-055408DOI Listing
May 2022

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial.

Lancet Haematol 2022 Jun 2;9(6):e415-e424. Epub 2022 May 2.

Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China; Zhejiang University Cancer Center, Hangzhou, Zhejiang, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China. Electronic address:

Background: Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18-74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.

Methods: We conducted a two-stage, single-arm, phase 2 trial at three public hospitals in China. We enrolled patients aged 18-60 years with previously untreated de novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received induction treatment with intravenous daunorubicin (60 mg/m on days 1-3), intravenous cytarabine (100 mg/m on days 1-7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6-11; DAV regimen). For induction therapy, the length of the treatment was 28-35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2000041509.

Findings: Between Dec 25, 2020, and July 7, 2021, 36 patients were assessed for eligibility and 33 were enrolled. 15 (45%) patients were men and 18 (55%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 91% (95% CI 76-98; 30 of 33 patients) in the entire cohort. 29 (97%) of 30 patients who reached complete remission had undetectable measurable residual disease (ie, <0·1%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 18 (55%), pneumonia in seven (21%), and sepsis in four (12%). No treatment-related deaths occurred. With a median follow-up of 11 months (IQR 9-12), estimated 1-year overall survival was 97% (95% CI 91-100) and 1-year event-free survival was 72% (56-94).

Interpretation: The DAV regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of complete remission. These findings are an important contribution to the field, showing a safe strategy to incorporate venetoclax into the most common induction regimen used to treat newly diagnosed acute myeloid leukaemia internationally.

Funding: Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, Key Research and Development Program of Zhejiang.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2352-3026(22)00106-5DOI Listing
June 2022

Zirconia/phenylsiloxane nano-composite for LED encapsulation with high and stable light extraction efficiency.

RSC Adv 2021 May 21;11(30):18326-18332. Epub 2021 May 21.

Key Laboratory of Green Printing, Institute of Chemistry, Chinese Academy of Sciences Beijing 100190 China

To obtain a rapid processible LED encapsulant that leads to high and stable light extraction efficiency (LEE), UV curable ZrO/phenyl-siloxane nano-composite (ZSC) double-layer encapsulants were prepared and optimized. The highly crystalline ZrO nanoparticles with a diameter of ∼14 nm were synthesized through a modified hydrothermal method at mild conditions, and a UV curable methacryl-diphenyl-polysiloxane (MDPS) with a refractive index (RI) of 1.54 (at 633 nm) was synthesized from self-condensation of diphenylsilanediol and an end-capping reaction. High refractive indexes (RIs) from 1.54-1.61 have been obtained for ZSC composites by adding 0-20 wt% ZrO. Before and after sulfur vapor erosion, the double-layer encapsulated sample (M-10/M) showed 11.2% and 64.8% higher LEE respectively than that of Dow Corning OE-7662. Meanwhile, the variation of LED light color temperature ( ) was less than 1%. The effect of the ZrO nanoparticle content on LEE of double-layer and single-layer encapsulation were compared and discussed based on Fresnel loss and Rayleigh scattering theories. The double-layered UV curing processing took only 1/6 of the time needed for common thermal curing.
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http://dx.doi.org/10.1039/d1ra02230jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033391PMC
May 2021
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