Publications by authors named "Liang Han"

658 Publications

Nanographene-Osmapentalyne Complexes as a Cathode Interlayer in Organic Solar Cells Enhance Efficiency over 18.

Adv Mater 2021 Jun 12:e2101279. Epub 2021 Jun 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.

Interface engineering is a critical method by which to efficiently enhance the photovoltaic performance of nonfullerene solar cells (NFSC). Herein, a series of metal-nanographene-containing large transition metal involving d -p conjugated systems by way of the addition reactions of osmapentalynes and p-diethynyl-hexabenzocoronenes is reported. Conjugated extensions are engineered to optimize the π-conjugation of these metal-nanographene molecules, which serve as alcohol-soluble cathode interlayer (CIL) materials. Upon extension of the π-conjugation, the power conversion efficiency (PCE) of PM6:BTP-eC9-based NFSCs increases from 16% to over 18%, giving the highest recorded PCE. It is deduced by X-ray crystallographic analysis, interfacial contact methods, morphology characterization, and carrier dynamics that modification of hexabenzocoronenes-styryl can effectively improve the short-circuit current density (J ) and fill factor of organic solar cells (OSCs), mainly due to the strong and ordered charge transfer, more matching energy level alignments, better interfacial contacts between the active layer and the electrodes, and regulated morphology. Consequently, the carrier transport is largely facilitated, and the carrier recombination is simultaneously impeded. These new CIL materials are broadly able to enhance the photovoltaic properties of OSCs in other systems, which provides a promising potential to serve as CILs for higher-quality OSCs.
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http://dx.doi.org/10.1002/adma.202101279DOI Listing
June 2021

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.

Nat Commun 2021 06 11;12(1):3579. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.
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http://dx.doi.org/10.1038/s41467-021-23681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196104PMC
June 2021

Prodrug Delivery Using Dual-Targeting Nanoparticles To Treat Breast Cancer Brain Metastases.

Mol Pharm 2021 Jun 10. Epub 2021 Jun 10.

Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.

Brain metastases from breast cancer are the most frequent brain metastasis in women, which are often difficult to be surgically removed due to the multifocal and infiltrative intracranial growth patterns. Cytotoxic drugs have potent anti-breast cancer properties. However, owing to the toxic side effects and the blood-brain barrier (BBB), these drugs cannot be fully and aggressively exploited with systemic administration and hence have very limited application for brain metastases. In this study, hyaluronidase-activated prodrug hyaluronic-doxorubicin (DOX) was assembled by the BBB and metastatic breast cancer dual-targeting nanoparticles (NPs), which were constructed based on transcytosis-targeting peptide and hyaluronic acid co-modified poly(lactic-co-glycolic acid)-poly(-carbobenzoxy-l-lysine). DOX showed enzyme-recovered DNA insertion, selective cytotoxicity to metastatic breast cancer cells rather than astrocytes, and efficient loading into dual-targeting NPs. [email protected] displayed the ability of dually targeting the BBB and metastatic breast cancer and significantly extended the median survival time of mice with intracranial metastatic breast cancer. Based on these improvements, this prodrug delivery tactic may serve as an important direction for drug therapy against brain metastases.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00224DOI Listing
June 2021

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.

Acta Pharm Sin B 2021 May 21;11(5):1341-1354. Epub 2020 Oct 21.

Jiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.
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http://dx.doi.org/10.1016/j.apsb.2020.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148067PMC
May 2021

Dual inhibition of cMET and EGFR by microRNA-338-5p suppresses metastasis of esophageal squamous cell carcinoma.

Carcinogenesis 2021 Jun 5. Epub 2021 Jun 5.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.

MicroRNAs, as a group of post-transcriptional regulators, regulate multiple pathological processes including metastasis during tumor development. Here, we demonstrated the metastasis-suppressive function of microRNA (miR)-338-5p in esophageal squamous cell carcinoma (ESCC). Overexpression of miR-338-5p had inhibitory effect on invasive ability of ESCC cells and extracellular matrix degradation, while silencing miR-338-5p had opposite effects. Mechanistically, miR-338-5p directly targeted the 3' untranslated regions of hepatocellular growth factor receptor cMet (cMET) and epidermal growth factor receptor (EGFR). As a result, miR-338-5p inhibited the downstream signaling cascades of cMET and EGFR, and repressed cMET- and EGFR-mediated ESCC cell invasion. Re-expression of cMET or EGFR in miR-338-5p overexpressing ESCC cells was sufficient to derepress ESCC cell invasion both in vitro and in vivo. We further showed that such manipulation downregulated the expression and secretion of matrix metalloproteinases 2 and 9, which resulted in impaired extracellular matrix degradation and cell invasion. Most importantly, systemic delivery of miR-338-5p mimic significantly inhibited metastasis of ESCC cells in nude mice. Taken together, our results uncovered a previously unknown mechanism through which miR-338-5p suppresses ESCC invasion and metastasis by regulating cMET/EGFR-MMP2/9 axis, and highlighted the potential significance of miR-338-5p-based therapy in treating patients with metastatic ESCC.
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http://dx.doi.org/10.1093/carcin/bgab046DOI Listing
June 2021

Open total dislocation of ankle joint without fractures: A case report.

Medicine (Baltimore) 2021 Jun;100(22):e26247

Department of Orthopedics, Affiliated Hospital of Jining Medical University, Jining City, Shandong Province, China.

Rationale: Open total dislocation of ankle joint is rare and often caused by high-energy injury. The present study describes a patient with open total lateral dislocation of ankle joint without fractures and obtained a satisfactory clinical result following early debridement and irrigation, one-stage repairment of ligaments, and plaster external fixation.

Patient Concerns: The patient, a 45-year-old male, complained of right foot pain with bleeding and limited motion. Physical examination showed a 15-cm open wound at the medial ankle region, with soft tissues impaired and ankle bones exposed. The 3 dimensional reconstruction computed tomography (CT) examination showed an open total dislocation of ankle joint without concomitant fractures.

Diagnoses: open total lateral dislocation of ankle joint without fractures.

Interventions: Early modern wound care including thorough debridement and irrigation on the wound was performed to remove contaminated soft tissues. Subsequently, the dislocated ankle joint was reduced by hand and the medial and lateral collateral ligaments were repaired using wire anchors.

Outcomes: The medial wound healed at 2 weeks after surgery, and several common complications such as infection and skin necrosis did not occur. The last follow-up showed a good range of metatarsal flexion and extension of the injured foot, and obvious signs of traumatic arthritis were not observed. According to Kaikkonen ankle function score, the patient was assessed with 90 points.

Lessons: For open total dislocation of ankle joint, early treatment should focus on debridement and irrigation, reduction and fixation of the dislocated ankle, protection of the weak soft tissues, and stable external fixation to promote wound healing and reduce the incidence of related complications.
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http://dx.doi.org/10.1097/MD.0000000000026247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183828PMC
June 2021

Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis.

J Ethnopharmacol 2021 May 20:114213. Epub 2021 May 20.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology. Electronic address:

Ethnopharmacological Relevance: Herba taxilli (HT, Sangjisheng in Chinese), which is composed of the dried stems and leaves of Taxillus chinensis (DC.) Danser, has been commonly used to treat inflammation and arthritis in traditional Chinese medicine (TCM). Quercetin (Que) is a major active flavonoid component isolated from HT and is one of the quality control indexes of HT. In the clinical practice of TCM, formulas containing HT are commonly used to treat rheumatoid arthritis (RA). Recent studies have shown that Que exerts antiarthritic effects. However, the mechanism by which Que treatment affects RA is not fully understood.

Aim Of The Study: This study aimed to explore the antiarthritic activity of Que in a collagen-induced arthritis (CIA) mouse model and investigate the underlying mechanisms.

Materials And Methods: The antiarthritic activity of Que was evaluated in a CIA mouse model by determining the paw clinical arthritis scores and left ankle thicknesses and by conducting micro-PET imaging and histopathological analysis of ankle joint tissues. The proinflammatory cytokine (IL-6, TNF-α, IL-1β, IL-8, IL-13, IL-17) levels in the serum and ankle joint tissues were measured by ELISA. Mitochondrial oxidative stress was assessed by biochemical methods. Mitochondrial biogenesis was analyzed by RT-qPCR. The protein levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), p38, phospho-p38, extracellular signal-regulated kinases (ERK)-1/2, phospho-ERK1/2, p65, and phospho-p65 in ankle joint tissues were detected by Western blot analysis. A total of 30 RA patients were recruited to investigate the relationship between the disease activity score (DAS28) and the SIRT1, PGC-1α, NRF1, and HMGB1 plasma levels.

Results: Que treatment decreased the clinical score and left ankle thickness of CIA mice, attenuated the synovial inflammation and hyperplasia and bone/cartilage destruction in ankle joints, and decreased the secretion of IL-6, TNF-α, IL-1β, IL-8, IL-13, and IL-17. Mechanistically, Que treatment improved impaired mitochondrial biogenesis and mitochondrial function by regulating the SIRT1/PGC-1α/NRF1/TFAM pathway and inhibited inflammation via the HMGB1/TLR4/p38/ERK1/2/NF-κB p65 pathway. Notably, epidemiological data revealed correlations between abnormal circulating levels of SIRT1, PGC-1α, NRF1, HMGB1 and RA disease activity in patients.

Conclusions: Our data suggested a potential role of Que as a dietary therapeutic drug for RA treatment that may act through SIRT1 to target mitochondrial biogenesis. Additionally, the role of impaired mitochondrial biogenesis in RA was evaluated.
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http://dx.doi.org/10.1016/j.jep.2021.114213DOI Listing
May 2021

[Treatment of irreducible intertrochanteric femoral fracture with minimally invasive clamp reduction technique via anterior approach].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 May;35(5):544-549

Department of Traumatic Orthopedics, Affiliated Hospital of Jining Medical University, Jining Shandong, 272029, P.R.China.

Objective: To explore the effectiveness of minimally invasive clamp reduction technique via anterior approach in treatment of irreducible intertrochanteric femoral fractures.

Methods: Between January 2015 and January 2019, 59 patients with irreducible intertrochanteric femoral fractures were treated with minimally invasive clamp reduction technique via anterior approach. There were 29 males and 30 females with an average age of 77.9 years (range, 45-100 years). The causes of injury included falling in 46 cases, traffic accident in 6 cases, smashing in 2 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.8 days). The fractures were classified as AO type 31-A1 in 12 cases, type 31-A2 in 25 cases, type 31-A3 in 22 cases.

Results: All fractures were reduced well and the fracture reduction took 10 to 30 minutes, with an average of 19 minutes. All patients were followed up 13-25 months, with an average of 17.6 months. Among them, 2 cases of pronation displacement of proximal fracture segment died for infection or falling pneumonia after internal fixation failed. Six patients with reversed intertrochanteric femoral fractures experienced re-pronation and abduction displacement of the lateral wall after internal fixation, but the fractures all healed. The rest of the patients had no fracture reduction loss, and the fractures healed with an average healing time of 5.9 months (range, 3-9 months). Except for 2 patients who died, the Harris score of hip joint function of the remaining 57 patients was excellent in 49 cases and good in 8 cases at last follow-up.

Conclusion: The minimally invasive clamp reduction technique via anterior approach for irreducible intertrochanteric femoral fractures is simple and effective. For irreducible intertrochanteric femoral fractures related to lateral wall displacement, after clamp reduction and intramedullary nail fixation, the lateral wall should be reinforced in order to avoid reduction loss and internal fixation failure.
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http://dx.doi.org/10.7507/1002-1892.202012030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175198PMC
May 2021

Structural characterization and Kemp eliminase activity of the Mycobacterium smegmatis Ketosteroid Isomerase.

Biochem Biophys Res Commun 2021 Jun 13;560:159-164. Epub 2021 May 13.

State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science and College of Life Sciences, Nankai University, Tianjin, 300071, China.

The Kemp elimination reaction, involving the ring-opening of benzoxazole and its derivatives under the action of natural enzymes or chemical catalysts, has been of interest to researchers since its discovery. Because this reaction does not exist in all currently known metabolic pathways, the computational design of Kemp eliminases has provided valuable insights into principles of enzymatic catalysis. However, it was discovered that the naturally occurring promiscuous enzymes ydbC, xapA and ketosteroid isomerase also can catalyze Kemp elimination. Here, we report the crystal structure of ketosteroid isomerase (KSI) from Mycobacterium smegmatis MC2 155. MsKSI crystallizes in the P222 space group with two molecules in an asymmetric unit, and ultracentrifugation data confirms that it forms a stable dimer in solution, consistent with the 1.9 Å-resolution structure. Our assays confirm that MsKSI accelerates the Kemp elimination of 5-nitrobenzoxazole (5NBI) with an optimal pH of 5.5. A 2.35 Å resolution crystal structure of the MsKSI-5NBI complex reveals that the substrate 5NBI is bound in the active pocket of the enzyme composed of hydrophobic residues. In addition, the Glu127 residue is proposed to play an important role as a general base in proton transfer and breaking weak O-N bonds to open the five-membered ring. This work provides a starting point for exploring the artificial modification of MsKSI using the natural enzyme as the backbone.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.007DOI Listing
June 2021

Colloidal quantum dots lasing and coupling in 2D holographic photonic quasicrystals.

Opt Express 2021 May;29(10):15145-15158

Global research on the solution-processable colloidal quantum dots (CQDs) constitutes outstanding model systems in nanoscience, micro-lasers, and optoelectronic devices due to tunable color, low cost, and wet chemical processing. The two-dimensional (2D) CQDs quasicrystal lasers are more efficient in providing coherent lasing due to radiation feedback, high-quality-factor optical mode, and long-range rotational symmetry. Here, we have fabricated a 2D quasicrystal exhibiting 10-fold rotational symmetry by using a specially design pentagonal prism in the optical setup of a simple and low-cost holographic lithography. We developed a general analytical model based on the cavity coupling effect, which can be used to explain the underlying mechanism responsible for the multi-wavelength lasing in the fabricated 2D CQDs holographic photonic quasicrystal. The multi-wavelength surface-emitting lasers such as λ = 629.27 nm, λ = 629.85 nm, λ = 629.06 nm, λ = 630.17 nm, and λ = 628.76 with a coupling constant κ = 0.38 achieved from the 2D holographic photonic quasicrystal are approximately similar with the developed analytical model based on cavity coupling effect. Moreover, the lasing patterns of the 2D CQDs photonic quasicrystal laser exhibit a symmetrical polarization effect by rotating the axis of polarization with a difference of 120 angle in a round trip. We expect that our findings will provide a new approach to customize the 2D CQDs holographic photonic quasicrystal lasers in the field of optoelectronic devices and miniature lasing systems.
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http://dx.doi.org/10.1364/OE.422288DOI Listing
May 2021

Development and Validation of a Novel Circulating miRNA-Based Diagnostic Score for Early Detection of Hepatocellular Carcinoma.

Dig Dis Sci 2021 May 12. Epub 2021 May 12.

Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People's Republic of China.

Background: With the rise of liquid biopsy in oncology, circulating miRNAs have become one of the most promising noninvasive biomarkers for early detection of hepatocellular carcinoma (HCC). However, a reliable HCC-related circulating miRNA panel and corresponding diagnostic model remain to be explored.

Methods: Five large public datasets related to intact miRNA profiles in the serum or tumors of HCC patients were included and divided into training cohorts (GSE113740 and TCGA-LIHC) and validation cohorts (GSE112264, GSE113486 and GSE106817). Compared with non-cancer controls and high-risk patients, key miRNAs dysregulated in both the serum and tumors of HCC patients were identified by differential expression analysis and overlapping analysis. The corresponding diagnostic model was constructed by LASSO logistic regression and evaluated by receiver operating characteristic curves and a nomogram with calibration plot.

Results: A distinctive panel of HCC-related circulating miRNAs, including three upregulated miRNAs (miR-184, miR-532-5p, miR-221-3p) and three downregulated miRNAs (miR-5589-5p, let-7b-3p, miR-26b-3p), were rigorously screened out, all of which displayed significant discriminability between HCC patients and controls (all P < 0.05). In addition, a reliable six-circulating miRNA-based diagnostic score was constructed and displayed robust diagnostic ability for HCC (particularly for early-stage HCC) (AUC = 0.9535, P < 0.05) compared with that of the serum α-fetoprotein test. Importantly, its efficacy was sufficiently validated in three independent datasets (AUC = 0.9780/0.9961/0.9681, all P < 0.05). Furthermore, a visual nomogram based on the diagnostic score was correspondingly established to strengthen its clinical applicability.

Conclusion: The six-circulating miRNA-based diagnostic score may be a reliable noninvasive biomarker for early-stage HCC screening and dynamic monitoring of postoperative recurrence.
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http://dx.doi.org/10.1007/s10620-021-07031-0DOI Listing
May 2021

Push or Pull Electrons: Acetoxy and Carbomethoxy-Substituted Isomerisms in Organic Solar Cell Acceptors.

J Phys Chem Lett 2021 May 12;12(19):4666-4673. Epub 2021 May 12.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Isomerism is a major factor affecting the properties of materials. Herein, two isomeric acceptors based on acetoxy and methyl ester end group substituents, and are reported. When blended with PBDB-TF, devices based on achieve an inferior (8.32%) power conversion efficiency (PCE) while the material has a superior PCE of 13.25%. We investigated the reasons why these two devices, which differ only in the isomeric substituents on the terminal site, have such a large difference in photovoltaic performance. Our investigation conducted theoretical calculations and examined UV-vis absorption, energy levels, exciton dissociation and bimolecular recombination, mobilities tests, photoluminescence, and packing modes. It is found that the energy levels of the materials are fine-tuned, the absorption spectra are adjusted, and the energy loss is regulated. Our studies explored the reasons for the properties of materials differing, and the acetoxy and carbomethoxy substitutions provided some useful information concerning high-performance acceptor materials.
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http://dx.doi.org/10.1021/acs.jpclett.1c01077DOI Listing
May 2021

A novel genomic model for predicting the likelihood of delayed graft function in DCD kidney transplantation.

Transl Androl Urol 2021 Apr;10(4):1637-1646

Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China.

Background: The high incidence of delayed graft function (DGF) following kidney transplantation with donation after cardiac death allografts (DCD-KT) poses great challenges to transplant clinicians. This study aimed to explore the DGF-related biomarkers and establish a genomic model for DGF prediction specific to DCD KT.

Methods: By data mining a public dataset (GSE43974), the key DGF-related genes in DCD kidney biopsies taken after short-time reperfusion (45-60 min) were identified by differential expression analysis and a LASSO-penalized logistic regression model. Their coefficients for modeling were calculated by multivariate logistic regression. Receiver operating characteristic curves and a nomogram were generated to evaluate its predictive ability for DGF occurrence. Gene set enrichment analysis (GSEA) was performed to explore biological pathways underlying DGF in DCD KT.

Results: Five key DGF-related genes (CHST3, GOLPH3, ZBED5, AKR1C4, and ERRFI1) were first identified, all of which displayed good discrimination for DGF occurrence after DCD KT (all P<0.05). A five-mRNA-based risk score was further established and showed excellent predictive ability (AUC =0.9708, P<0.0001), which was obviously higher than that of the five genes alone. Eight DGF-related biological pathways in DCD kidneys, such as "arachidonic acid metabolism", "lysosome", "proximal tubule bicarbonate reclamation", "glutathione metabolism", were identified by GSEA (all P<0.05). Moreover, a convenient and visual nomogram based on the genomic risk score was also constructed and displayed high accuracy for DGF prediction specific to DCD KT.

Conclusions: The novel genomic model may effectively predict the likelihood of DGF immediately after DCD KT or even prior to transplantation in the context of normothermic machine perfusion in the future.
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http://dx.doi.org/10.21037/tau-20-1533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100846PMC
April 2021

Establishment and verification of prognostic model for gastric cancer based on autophagy-related genes.

Am J Cancer Res 2021 15;11(4):1335-1346. Epub 2021 Apr 15.

Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer Tianjin 300060, P. R. China.

Autophagy played a significant role in the development of cancer. In this study, we explored the value of autophagy-associated genes in gastric cancer. RNA sequencing and clinical information containing 375 gastric cancer and 32 normal tissues were gathered from the TCGA portal. Then we stochastically allocated the autophagy-associated genes (AAGs) to training and testing groups. Next, we screened the discrepantly expressed AAGs and the prognostic AAGs by Cox regression analysis and Lasso regression analysis. Afterwards, we structured the model by using the prognostic AAGs and plotted Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves to verify the performance of models in both groups. Besides, we utilized Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular mechanisms of AAGs in gastric cancer. Finally, we demonstrated discrepant expression of AAGs within gastric cancer and non-tumor tissues at protein level with immunohistochemistry. 28 discrepantly expressed AAGs were screened from the TCGA database which contained 375 gastric cancer and 32 non-tumor samples. Cox and Lasso regression analyses were performed in training group and then we got 5 prognostic AAGs to establish the prognostic model. The patients who had high risk possessed worse overall survival (OS) both in training group (5-year OS, 47.6% vs 23.1%; P < 0.0001) and test group (5-year OS, 49.2% vs 0%, P=0.019). The proportion under ROC curves (AUC) were significant both in training group and test group (5-year AUC, 0.736 vs 0.809). Through this study, we constructed a model for gastric cancer patients which may provide individual treatment and superior prognosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085875PMC
April 2021

DNMT3A-mediated silence in ADAMTS9 expression is restored by RNF180 to inhibit viability and motility in gastric cancer cells.

Cell Death Dis 2021 Apr 30;12(5):428. Epub 2021 Apr 30.

Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.

ADAMTS9 belongs to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family, and its expression is frequently silenced due to promoter hypermethylation in various human cancers. However, the underlying mechanisms remain largely unknown. In this study, we investigated the inhibitory effects of ADAMTS9 on gastric cancer (GC) cells. We initially examined ADAMTS9 protein level in 135 GC and adjacent normal tissue pairs, showing that ADAMTS9 was strikingly decreased in the malignant specimens and patients with low ADAMTS9 expression exhibited more malignant phenotypes and poorer outcome. ADAMTS9 expression was restored in AGS and BGC-823 cells, which then markedly suppressed cellular viability and motility in vitro and in vivo. As ADAMTS9 was enriched in the nuclei of gastric mucosal cells, RNA-sequencing experiment showed that ADAMTS9 significantly altered gene expression profile in BGC-823 cells. Additionally, DNA methyltransferase 3α (DNMT3A) was identified to be responsible for the hypermethylation of ADAMTS9 promoter, and this methyltransferase was ubiquitinated by ring finger protein 180 (RNF180) and then subject to proteasome-mediated degradation. In conclusion, we uncovered RNF180/DNMT3A/ADAMTS9 axis in GC cells and showed how the signaling pathway affected GC cells.
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http://dx.doi.org/10.1038/s41419-021-03628-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087691PMC
April 2021

LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target.

Oncogene 2021 May 21;40(19):3422-3433. Epub 2021 Apr 21.

Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.

Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.
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http://dx.doi.org/10.1038/s41388-021-01656-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116207PMC
May 2021

MrgprC11 sensory neurons mediate glabrous skin itch.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332

Itch arising from glabrous skin (palms and soles) has attracted limited attention within the field due to the lack of methodology. This is despite glabrous itch arising from many medical conditions such as plantar and palmar psoriasis, dyshidrosis, and cholestasis. Therefore, we developed a mouse glabrous skin behavioral assay to investigate the contribution of three previously identified pruriceptive neurons in glabrous skin itch. Our results show that MrgprA3 and MrgprD neurons, although key mediators for hairy skin itch, do not play important roles in glabrous skin itch, demonstrating a mechanistic difference in itch sensation between hairy and glabrous skin. We found that MrgprC11 neurons are the major mediators for glabrous skin itch. Activation of MrgprC11 neurons induced glabrous skin itch, while ablation of MrgprC11 neurons reduced both acute and chronic glabrous skin itch. Our study provides insights into the mechanisms of itch and opens up new avenues for future glabrous skin itch research.
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http://dx.doi.org/10.1073/pnas.2022874118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053975PMC
April 2021

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX).

J Cancer Res Clin Oncol 2021 Apr 17. Epub 2021 Apr 17.

Nanjing Personal Oncology Biological Technology Co. Ltd, Nanjing, Jiangsu, China.

Background: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers.

Methods: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis.

Results: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens.

Conclusion: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.
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http://dx.doi.org/10.1007/s00432-021-03639-xDOI Listing
April 2021

Well differentiated carcinoma with a poor prognosis: a retrospective analysis of papillary gastric adenocarcinoma.

Surg Today 2021 Apr 16. Epub 2021 Apr 16.

Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Cancer for Cancer, Tianjin, 300060, China.

Purpose: To explore the clinicopathological features and prognosis of papillary gastric adenocarcinoma (PGC).

Methods: The subjects of this retrospective analysis were 1525 patients with gastric cancer in a single center in China.

Results: The patients with PGC were generally of advanced age and the tumor was located in the upper 1/3 of the stomach. PGC was well or moderately differentiated, with serosal infiltration, early lymph node metastasis, TNM stages I/II, liver metastasis, and a short postoperative overall survival time. Patients with the secondary pathological type of papillary adenocarcinoma presented with clinicopathological similarities to those with primary PGC. PGC was a risk factor for poor survival in both univariate and multivariate analyses.

Conclusion: Papillary gastric adenocarcinoma (PGC) showed different clinicopathological characteristics and prognosis to other types of gastric cancer (GC), even if it was not the primary pathological type. The higher the proportion of papillary adenocarcinoma in gastric cancer samples, the shorter the postoperative survival time of patients. PGC needs further multicenter studies.
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http://dx.doi.org/10.1007/s00595-021-02289-3DOI Listing
April 2021

A four-gene signature predicts survival and anti-CTLA4 immunotherapeutic responses based on immune classification of melanoma.

Commun Biol 2021 Mar 22;4(1):383. Epub 2021 Mar 22.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Cutaneous melanoma is the most malignant skin cancer. Biomarkers for stratifying patients at initial diagnosis and informing clinical decisions are highly sought after. Here we classified melanoma patients into three immune subtypes by single-sample gene-set enrichment analysis. We further identified a four-gene tumor immune-relevant (TIR) signature that was significantly associated with the overall survival of melanoma patients in The Cancer Genome Atlas cohort and in an independent validation cohort. Moreover, when applied to melanoma patients treated with the CTLA4 antibody, ipilimumab, the TIR signature could predict the response to ipilimumab and the survival. Notably, the predictive power of the TIR signature was higher than that of other biomarkers. The genes in this signature, SEL1L3, HAPLN3, BST2, and IFITM1, may be functionally involved in melanoma progression and immune response. These findings suggest that this four-gene signature has potential use in prognosis, risk assessment, and prediction of anti-CTLA4 response in melanoma patients.
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http://dx.doi.org/10.1038/s42003-021-01911-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985195PMC
March 2021

Generation and application of a monoclonal antibody against the 18-kDa oncosphere antigen of Taenia pisiformis.

Exp Parasitol 2021 May 17;224:108096. Epub 2021 Mar 17.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China. Electronic address:

Taenia pisiformis is a parasite that causes cysticercosis pisiformis, which has acquired economic relevance because of its effects on animal welfare and production. A useful assay for the detection of T. pisiformis is needed for the prevention of cysticercosis pisiformis and control of the parasite. The 18-kDa oncosphere antigen is expressed in the oncosphere of several cysticerci in species of the genus Taenia, including T. pisiformis. This protein plays an important role in tissue invasion and has extensive applications in diagnosis. In this study, the T. pisiformis 18-kDa oncosphere antigen (TPO18) was expressed in soluble form and successfully purified for use in the production of monoclonal antibodies (MAbs) against TPO18. Twenty hybridomas were obtained using ELISA, and the subcloning process identified three positive hybridoma cell lines, which were designated as 4E8, 5G5, and 7E8. MAb 7E8 exhibited the highest titer and had an IgG2b heavy chain and a kappa light chain. Western blot analysis demonstrated that MAb 7E8 reacted with GST-TPO18. Immunohistochemistry showed that TPO18 was widely distributed in the drape and wall of uteri in adults of T. pisiformis adults and in the fibrous layer of the sucker and cyst cavity of T. pisiformis cysticerci. This research will provide a foundation for the development of diagnostic tools and will contribute to a better understanding of the functions of TPO18.
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http://dx.doi.org/10.1016/j.exppara.2021.108096DOI Listing
May 2021

More reliable breast cancer risk assessment for every woman.

Authors:
Han Liang

Cancer Cell 2021 Apr 18;39(4):457-459. Epub 2021 Mar 18.

Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Using large, unbiased cohorts, two studies in The New England Journal of Medicine assessed the associations between germline variants in putative cancer susceptibility genes and the risk of breast cancer. They consistently identified a small set of genes as being the most informative for risk prediction, helping select high-risk women in the general population, and developing effective cancer prevention strategies.
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http://dx.doi.org/10.1016/j.ccell.2021.02.018DOI Listing
April 2021

Overcoming Mfsd2a-Mediated Low Transcytosis to Boost Nanoparticle Delivery to Brain for Chemotherapy of Brain Metastases.

Adv Healthc Mater 2021 05 18;10(9):e2001997. Epub 2021 Mar 18.

Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, 215123, China.

Microvessels of the blood-brain barrier (BBB) exclusively express the major facilitator superfamily domain-containing protein 2a (Mfsd2a), which is the key transporter for docosahexaenoic acid uptake into the brain. Mfsd2a suppresses caveolae-mediated transcytosis to regulate BBB transcellular permeability via controlling lipid composition of BBB endothelial cells. It is speculated that Mfsd2a can restrain BBB crossing efficiency and brain accumulation efficiency of brain-targeting drug delivery systems, which penetrate the BBB often through the receptor-mediated transcytosis pathway. Transcytosis across the BBB is a crucial bottleneck for targeted chemotherapy of brain metastases. To overcome this issue, a pair of priming nanoparticles (NPs) and following drug-loaded NPs are designed. Tunicamycin-(TM)-loaded transcytosis-targeting-peptide-(TTP)-decorated NPs ([email protected]) are used to boost BBB transcytosis via inhibiting Mfsd2a. Doxorubicin (DOX)-loaded TTP and CD44-specific hyaluronic acid (HA)-comodified NPs ([email protected]) are designed as following drug-loaded NPs. The brain accumulation efficacy of following [email protected] with priming is 4.30-fold higher than that without priming through the enhanced transcytosis pathway rather than the tight junction opening. Effective BBB crossing and brain accumulation, selective tumor uptake, excellent antitumor efficacy, and low hepatotoxicity are achieved by [email protected] and [email protected], suggesting this tactic as a significant therapeutic strategy against breast cancer brain metastases.
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http://dx.doi.org/10.1002/adhm.202001997DOI Listing
May 2021

Molecular Mechanism of the ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuronal Apoptosis in SPS Rats.

J Mol Neurosci 2021 Mar 18. Epub 2021 Mar 18.

PTSD Laboratory, Department of Histology and Embryology, School of Basic Medicine, China Medical University, Shenyang, China.

Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also an important cause of memory impairment in PTSD patients. Endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α (ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. A PTSD rat model was constructed by the single prolonged stress (SPS) method. The study was divided into three parts. Experiment 1 included the control group, SPS 1 d group, SPS 7 d group, and SPS 14 d group. Experiment 2 included the control group, SPS 7 d group, SPS 7 d + AEBSF group, and control + AEBSF group. (4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor). Experiment 3 included the control group, SPS 4 d group, SPS 4 d + AEBSF group, and control + AEBSF group. The protein and mRNA expression levels of ATF6α, glucose-regulated protein (GRP78), S1P, S2P, C/EBP homologous protein (CHOP), and caspase-12 in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. Apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α and GRP78 increased gradually in the SPS 1 d group and the SPS 7 d group but decreased in the SPS 14 d group (P < 0.01). In experiment 2, compared with that in the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were significantly increased in the SPS 7 d group (P < 0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were significantly decreased after AEBSF pretreatment (P < 0.01). In experiment 3, compared with that in the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were increased in the SPS 14 d group (P < 0.05). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were decreased after AEBSF pretreatment (P < 0.05). SPS induced apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.
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http://dx.doi.org/10.1007/s12031-021-01823-9DOI Listing
March 2021

A novel PMP22 insertion mutation causing Charcot-Marie-Tooth disease type 3: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e25163

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.

Rationale: Charcot-Marie-Tooth disease (CMT) is a group of hereditary neuropathies with clinical features of muscle atrophy, sensory loss, and foot deformities. CMT is related to a number of genes, such as peripheral myelin protein 22 gene (PMP22). Missense mutations, small deletion mutations, and duplications of PMP22 are common in CMT patients, but few insertion mutation cases of PMP22 have been reported.

Patient Concerns: A 26-year-old male patient with the complaint of general weakness, peroneal atrophy, and deformities in the extremities visited our hospital. The patient was born with bilateral thumbs and feet dystonia. Additionally, delayed feet arch development and delayed walking was observed when he was a child.

Diagnosis: Using whole-exome sequencing and electrophysiological test, we identified a novel insertion mutation of PMP22 (NM_153322, c.54_55insGTGCTG, p.(L19delinsVLL)) in a 26-year-old male patient with peroneal atrophy and nerve conduction was not elicited in electromyography (EMG) study. The Protein Variation Effect Analyzer (PROVEAN) program analysis predicted that the variant is likely to be "deleterious." SWISS-MODEL program predicted that alpha helix in original location was disrupted by inserted 6 bases, which may account for the occurrence of CMT3.

Interventions: The patient received symptomatic and supportive treatments, and routine rehabilitation exercises during hospitalization.

Outcomes: The condition of the patient was improved, but the disease could not be cured. At 1- and 3-months follow-up, manifestations of the patient were unchanged, and he could take care of himself.

Lessons: Our findings link a novel PMP22 mutation with a clinical diagnosis of CMT3. The link between gene variation and CMT phenotype may help to reveal the structure and function of PMP22 protein and the pathogenesis of CMT. This study adds further support to the heterogeneity of PMP22 related CMT and provides solid functional evidence for the pathogenicity of the p.(L19delinsVLL) PMP22 variant. Moreover, with the development of high-throughput sequencing technology, the combination of next-generation sequencing (NGS) and conventional Sanger sequencing is becoming one of the comprehensive, inexpensive, and convenient tools for genetic diagnosis of CMT.
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http://dx.doi.org/10.1097/MD.0000000000025163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982204PMC
March 2021

Effects of a high body mass index on the short-term outcomes and prognosis after radical gastrectomy.

Surg Today 2021 Mar 10. Epub 2021 Mar 10.

Department of Gastric Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, West Huan-Hu Rd, Ti Yuan Bei, Hexi District, Tianjin, 300060, China.

Purpose: This study aimed to investigate the effects of a high body mass index (BMI) on the outcomes of radical gastrectomy for gastric cancer.

Methods: We conducted a retrospective cohort study of 1729 patients with stage I to III gastric cancer who received open radical gastrectomy from February 2003 to August 2011. The patients were divided into 3 groups according to their BMI: a low BMI group (BMI < 18.5 kg/m), normal BMI group (18.5 ≤ BMI < 25 kg/m), and high BMI group (BMI ≥ 25 kg/m).

Results: A total of 871 patients were included in the final analysis, of which the median BMI was 22.7 kg/m (range 13.6-44.9 kg/m). A high BMI increased the risk of postoperative intestinal fistula but not the risk of a reduced number of examined lymph nodes or hospital death. Furthermore, a high BMI did not negatively affect the overall survival (OS) of gastric cancer patients.

Conclusions: A high BMI increased the operative morbidity after radical gastrectomy for gastric cancer. However, a high BMI did not negatively affect the quality of lymphadenectomy or the OS of gastric cancer patients in experienced high-volume centers. A careful approach during operation and meticulous perioperative management are required for gastric cancer patients with a high BMI.
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http://dx.doi.org/10.1007/s00595-021-02259-9DOI Listing
March 2021

Chlorinated Benzo[1,2-b:4,5-c']dithiophene-4,8-dione Polymer Donor: A Small Atom Makes a Big Difference.

Adv Sci (Weinh) 2021 Feb 4;8(4):2003641. Epub 2021 Jan 4.

Shenzhen Grubbs Institute and Department of Chemistry Southern University of Science and Technology Shenzhen 518055 China.

The position of a chlorine atom in a charge carrier of polymer solar cells (PSCs) is important to boost their photovoltaic performance. Herein, two chlorinated D-A conjugated polymers PBBD-Cl-α and PBBD-Cl-β are synthesized based on two new building blocks (TTO-Cl-α and TTO-Cl-β) respectively by introducing the chlorine atom into α or β position of the upper thiophene of the highly electron-deficient benzo[1,2-b:4,5-c']dithiophene-4,8-dione moiety. Single-crystal analysis demonstrates that the chlorine-free TTO shows a π-π stacking distance () of 3.55 Å. When H atom at the α position of thiophene of TTO is replaced by Cl, both π-π stacking distance ( = 3.48 Å) and Cl···S distance ( = 4.4 Å) are simultaneously reduced for TTO-Cl-α compared with TTO. TTO-Cl-β then showed the Cl···S non-covalent interaction can further shorten the intermolecular π-π stacking separation to 3.23 Å, much smaller than that of TTO-Cl-α and TTO. After blending with BTP-eC9, PBBD-Cl-β:BTP-eC9-based PSCs achieved an outstanding power conversion efficiency (PCE) of 16.20%, much higher than PBBD:BTP-eC9 (10.06%) and PBBD-Cl-α:BTP-eC9 (13.35%) based devices. These results provide an effective strategy for design and synthesis of highly efficient donor polymers by precise positioning of the chlorine substitution.
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http://dx.doi.org/10.1002/advs.202003641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887605PMC
February 2021

The antibacterial activities of MoS nanosheets towards multi-drug resistant bacteria.

Chem Commun (Camb) 2021 Mar 23;57(24):2998-3001. Epub 2021 Feb 23.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

We demonstrated that molybdenum disulfide (MoS) nanosheets can be an excellent solar disinfection agent for multi-drug resistant (MDR) bacteria with disinfection efficiencies >99.9999% in only 30 min. Distinct from other reactive oxygen species (ROS)-dependent photocatalysts, both ROS generation and size decrease contributed to the high antibacterial efficiencies of MoS.
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http://dx.doi.org/10.1039/d1cc00327eDOI Listing
March 2021

Involvement of the BNP/NPR-A/BKCa pathway in rat trigeminal ganglia following chronic constriction injury.

J Neurophysiol 2021 04 17;125(4):1139-1145. Epub 2021 Feb 17.

Key Lab of Oral Diseases Research of Anhui Province, Stomatologic Hospital & College, Anhui Medical University, Hefei, People's Republic of China.

Accumulating evidence indicates that the brain natriuretic peptide (BNP) and its receptor (natriuretic peptide receptor, NPR) are widely distributed in a variety of tissues including trigeminal ganglion (TG). Furthermore, recent studies support the involvement of the BNP-NPR-A pathway in acute and chronic pain. To investigate the role of this pathway in chronic pain, an infraorbital nerve-chronic constriction injury (ION-CCI) model of trigeminal neuralgia (TN) was produced in the rat. The time course of changes in mechanical pain threshold was examined. We observed an upregulation of BNP and NPR-A and a downregulation of large-conductance Ca-activated K (BKCa) mRNA and protein in rats subjected to ION-CCI. Patch clamping experiments in vitro found that BKCa currents were significantly reduced in rats subjected to ION-CCI. BNP increased BKCa currents in ION-CCI rats. These results suggest that BNP and NPR-A might serve as endogenous pain relievers in ION-CCI rats. Modulation of the BNP/NPR-A/BKCa channel pathway in TG may be a viable strategy for the treatment of TN. BNP has been known to activate its receptor, NPR-A, to modulate inflammatory pain. However, the potential modulatory roles of BNP in TN have not been investigated in detail. We established an ION-CCI model of TN in the rat and observed an upregulation of BNP and NPR-A and a downregulation of BKCa in rats subjected to ION-CCI. Moreover, BNP can increase BKCa currents in ION-CCI rats. Thus, BNP and NPR-A might have inhibitory effects on trigeminal neuralgia through activating the BNP/NPR-A/BKCa channel pathway.
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http://dx.doi.org/10.1152/jn.00682.2020DOI Listing
April 2021