Publications by authors named "Hong Zhou"

1,867 Publications

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Regulating Vacuum Tribological Behavior of a-C:H Film by Interfacial Activity.

J Phys Chem Lett 2021 Oct 19:10333-10338. Epub 2021 Oct 19.

Key Laboratory of Science and Technology on Wear and Protection of Materials, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

A hydrogenated amorphous carbon (a-C:H) film shows an ultralow friction coefficient (COF, lower than 0.01); however, its wear life is short in vacuum, and the mechanisms are still not well-understood. This study demonstrates the vacuum tribological behaviors of the a-C:H film can be regulated by interfacial activity. The strong interfacial activity induced continuous transfer of carbon from the film to counterface, causing the formation of a porous transfer film and severe wear of the a-C:H film. Interestingly, weak interfacial activity is beneficial to form spherical-like carbon at the sliding interface, which shields the interaction of dangling bonds and contributes to lower COF and wear of film. Notably, the catalytic nature of Au induced perfect graphene nanoscrolls around Au nanoparticles at the sliding interface, achieving ultralong vacuum wear life. This Letter unifies the understanding of vacuum tribological properties of a-C:H film and provides new insight for prolonging the life of carbon films in vacuum.
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http://dx.doi.org/10.1021/acs.jpclett.1c02841DOI Listing
October 2021

Differences in State Traumatic Brain Injury-Related Deaths, by Principal Mechanism of Injury, Intent, and Percentage of Population Living in Rural Areas - United States, 2016-2018.

MMWR Morb Mortal Wkly Rep 2021 Oct 15;70(41):1447-1452. Epub 2021 Oct 15.

Division of Injury Prevention, National Center for Injury Prevention and Control, CDC.

Traumatic brain injuries (TBIs) have contributed to approximately one million deaths in the United States over the last 2 decades (1). CDC analyzed National Vital Statistics System (NVSS) mortality data for a 3-year period (2016-2018) to examine numbers and rates of TBI-related deaths, the percentage difference between each state's rate and the overall U.S. TBI-related death rate, leading causes of TBI, and the association between TBI and a state's level of rurality. During 2016-2018, a total of 181,227 TBI-related deaths (17.3 per 100,000 population per year) occurred in the United States. The percentage difference between state TBI-related death rates and the overall U.S. rate during this period ranged from 46.2% below to 101.2% above the overall rate. By state, the lowest rate was in New Jersey (9.3 per 100,000 population per year); the states with the highest rates were Alaska (34.8), Wyoming (32.6), and Montana (29.5). States in the South and those with a higher proportion of residents living in rural areas had higher rates, whereas states in the Northeast and those with a lower proportion of residents living in rural areas had lower TBI-related death rates. In 43 states, suicide was the leading cause of TBI-related deaths; in other states, unintentional falls or unintentional motor vehicle crashes were responsible for the highest numbers and rates of TBI-related deaths. Consistent with previous studies (2), differences in TBI incidence and outcomes were observed across U.S. states; therefore, states can use these findings to develop and implement evidence-based prevention strategies, based on their leading causes of TBI-related deaths. Expanding evidence-based prevention strategies that address TBI-related deaths is warranted, especially among states with high rates due to suicide, unintentional falls, and motor vehicle crashes.
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http://dx.doi.org/10.15585/mmwr.mm7041a3DOI Listing
October 2021

Publisher Correction: Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.

Nat Commun 2021 Oct 13;12(1):6083. Epub 2021 Oct 13.

Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

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http://dx.doi.org/10.1038/s41467-021-26412-7DOI Listing
October 2021

Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy.

BMC Cardiovasc Disord 2021 Oct 13;21(1):495. Epub 2021 Oct 13.

Department of Physiology, Nanjing Medical University, 101 Longmian Road, Nanjing, 211166, Jiangsu, China.

Background: Arterial medial calcification (AMC) is associated with a high incidence of cardiovascular risk in patients with type 2 diabetes and chronic kidney disease. Here, we tested whether hydrogen sulfide (HS) can prevent AMC in rats with diabetic nephropathy (DN).

Methods: DN was induced by a single injection of streptozotocin and high-fat diet (45% kcal as fat) containing 0.75% adenine in Sprague-Dawley rats for 8 weeks.

Results: Rats with DN displayed obvious calcification in aorta, and this was significantly alleviated by Sodium Hydrosulfide (NaHS, a HS donor, 50 μmol/kg/day for 8 weeks) treatment through decreasing calcium and phosphorus content, ALP activity and calcium deposition in aorta. Interestingly, the main endogenous HS generating enzyme activity and protein expression of cystathionine-γ-lyase (CSE) were largely reduced in the arterial wall of DN rats. Exogenous NaHS treatment restored CSE activity and its expression, inhibited aortic osteogenic transformation by upregulating phenotypic markers of smooth muscle cells SMα-actin and SM22α, and downregulating core binding factor α-1 (Cbfα-1, a key factor for bone formation), protein expressions in rats with DN when compared to the control group. NaHS administration also significantly reduced Stat3 activation, cathepsin S (CAS) activity and TGF-β1 protein level, and improved aortic elastin expression.

Conclusions: HS may have a clinical significance for treating AMC in people with DN by reducing Stat3 activation, CAS activity, TGF-β1 level and increasing local elastin level.
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http://dx.doi.org/10.1186/s12872-021-02307-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515673PMC
October 2021

Laser-assisted selection of immotile spermatozoa has no effect on obstetric and neonatal outcomes of TESA-ICSI pregnancies.

Reprod Biol Endocrinol 2021 Oct 12;19(1):159. Epub 2021 Oct 12.

Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530003, China.

Background: Azoospermic patients have benefited from both epididymal and testicular spermatozoa intracytoplasmic sperm injection (ICSI) treatment and lasers have been used to identify viable, immotile spermatozoa before the procedure. There are limited studies on the safety of laser-assisted selection of immotile spermatozoa. The aim of this study was to investigate the impact of laser-assisted selection of immotile spermatozoa on the obstetric and neonatal outcomes after ICSI.

Methods: A retrospective comparative study was conducted on outcomes of ICSI cycles with testicular spermatozoa from June 2014 to June 2018. Of 132 cycles, 33 were allocated to the test group and oocytes were injected with immotile spermatozoa selected by laser, 99 cycles were allocated as control group.

Results: Compared with the control group, no significant differences were found in the pregnancy, implantation, miscarriage and live birth rates in the test group in either fresh or frozen transfer cycles. The cumulative live birth rate in the test group was 69.70%, which was slightly higher than in the control group (60.61%), but this was not statistically different. There were no differences in the average gestational age, premature birth rate, neonatal birth weight, and the malformation rate between the test and control groups (P > 0.05). In addition, the obstetric outcome between the two groups were not different (P > 0.05).

Conclusions: No negative effect on perinatal and neonatal outcomes was seen by using laser-assisted selection of immotile spermatozoa for TESA-ICSI. This study endorses the use of laser-assisted selection of viable spermatozoa for ICSI cycles.
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http://dx.doi.org/10.1186/s12958-021-00835-9DOI Listing
October 2021

Intimate Partner Violence against Women Living in Inadequate Conditions in Sub-Saharan Africa: A Meta-Analysis of Demographic and Health Survey Data.

Int J Environ Res Public Health 2021 09 27;18(19). Epub 2021 Sep 27.

Department of Maternal and Child Health, School of Public Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China.

Intimate partner violence (IPV) against women is a major public health problem and is widespread in sub-Saharan Africa (SSA). However, little is known about its environmental determinants. This study aimed to investigate whether inadequate living conditions are associated with IPV victimization in women in SSA. We analyzed cross-sectional data for 102,714 women in 25 SSA countries obtained from the Demographic and Health Surveys Program. Logistic regression was used to estimate the country-specific effects of inadequate living conditions (housing with at least one of four characteristics of unimproved water, unimproved sanitation, insufficient space, and unfinished materials) on multiple forms of IPV. Random effects meta-analysis was used to combined the country-specific estimates. We found an association between inadequate living conditions and a higher likelihood of experiencing any (OR = 1.12, 95% CI 1.03 to 1.23, = 0.012), sexual (OR = 1.18, 95% CI 1.05 to 1.34, = 0.008), emotional (OR = 1.12, 95% CI 1.02 to 1.23, = 0.023), and physical (OR = 1.15, 95% CI 1.03 to 1.28, = 0.010) IPV. The associations were stronger for rural and less-educated women. These findings suggest that future research to establish a causal link between living conditions and IPV and to elucidate the underlying pathways is crucial to design IPV interventions in SSA.
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http://dx.doi.org/10.3390/ijerph181910138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507939PMC
September 2021

Ganoderic Acids Prevent Renal Ischemia Reperfusion Injury by Inhibiting Inflammation and Apoptosis.

Int J Mol Sci 2021 Sep 23;22(19). Epub 2021 Sep 23.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Renal ischemia reperfusion injury (RIRI) is one of the main causes of acute kidney injury (AKI), which can lead to acute renal failure. The development of RIRI is so complicated that it involves many factors such as inflammatory response, oxidative stress and cell apoptosis. Ganoderic acids (GAs), as one of the main pharmacological components of , have been reported to possess anti-inflammatory, antioxidant, and other pharmacological effects. The study is aimed to investigate the protective effect of GAs on RIRI and explore related underlying mechanisms. The mechanisms involved were assessed by a mouse RIRI model and a hypoxia/reoxygenation model. Compared with sham-operated group, renal dysfunction and morphological damages were relieved markedly in GAs-pretreatment group. GAs pretreatment could reduce the production of pro-inflammatory factors such as IL-6, COX-2 and iNOS induced by RIRI through inhibiting TLR4/MyD88/NF-kB signaling pathway. Furthermore, GAs reduced cell apoptosis via the decrease of the ratios of cleaved caspase-8 and cleaved caspase-3. The experimental results suggest that GAs prevent RIRI by alleviating tissue inflammation and apoptosis and might be developed as a candidate drug for preventing RIRI-induced AKI.
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http://dx.doi.org/10.3390/ijms221910229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508562PMC
September 2021

Mechanism of the Passage of across the Final Host Blood-Brain Barrier Using the Next-Generation Sequencing.

Iran J Parasitol 2021 Jul-Sep;16(3):454-463

School of Medicine, Huzhou University, Huzhou Cent Hosp, Zhejiang, China.

Background: Multicellular parasites larvae develop in the final host rat brain at the fourth stage (L4) and migrate to the lungs by the adult stage. The potential mechanism of its blood-brain barrier (BBB) passage remains unclear.

Methods: By using Illumina Hiseq/Miseq sequencing, we obtained the transcriptomes of 3 groups of adult males and 3 groups of female of to generate similarly expressed genes (SEGs) between 2 genders at the adult stage. Next 2 groups of L4 expressed genes were used to compared with SEGs to create differentially expressed genes (DEGs) between 2 life stages to unlock potential mechanism of BBB passage.

Results: In total, we obtained 381 581 802 clean reads and 56 990 699 010 clean bases. Of these, 331 803 unigenes and 482 056 transcripts were successfully annotated. A total of 3 166 DEGs between L4 and adults SEGs were detected. Annotation of these DEGs showed 167 were down-regulated and 181 were up-regulated. Pathway analysis exhibited that calcium signaling pathway, the ECM-receptor interaction, focal adhesion, and cysteine and methionine metabolism were highly associated with DEGs. The function of these pathways might be related to BBB traversal, as well as neuro-regulation, interactions between parasite and host, environmental adaption.

Conclusion: This study expanded the regulatory characteristics of the two important life stages of . This information may provide a better appreciation of the biological features of the stages of the parasitic .
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http://dx.doi.org/10.18502/ijpa.v16i3.7099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476730PMC
February 2021

Downregulation of MicroRNA-145-5p in Activated Microglial Exosomes Promotes Astrocyte Proliferation by Removal of Smad3 Inhibition.

Neurochem Res 2021 Oct 8. Epub 2021 Oct 8.

Department of Orthopedics, Affiliated Hospital of Nantong University, 20th Xisi Road, Nantong, 226001, Jiangsu, China.

In spinal cord injury, microglial activation plays an important role during the inflammatory process. Specifically, the cellular and molecular interactions between microglia and astrocytes are of critical importance. Cells can communicate with each other through the substances carried by exosomes, and overproliferated astrocytes would create a physical and chemical barrier that prevents neurite regeneration, thereby interfering with functional recovery. On the other hand, Smad3 is an important factor in the proliferation, migration, and apoptosis of astrocytes. In this study, supernatant and purified exosomes were collected from LPS-treated microglia and co-cultured with astrocytes. The results showed that astrocytic proliferation was promoted with higher levels of Smad3. Furthermore, miRNA sequencing analysis was performed on microglial exosomes after inflammation. The results revealed a differential expression of miR-145-5p in the exosomes. The Dual-Luciferase assay showed that miR-145-5p could bind to Smad3 mRNA and regulate the levels of Smad3 protein at the post-transcriptional level. Subsequently, exosomes were transfected with miR-145-5p mimics, and astrocytes after mechanical injury were cultured with these exosomes for 24 h. The levels of Smad3 and phosphor-Smad3 proteins were analyzed by western blot and qRT-PCR. CCK8 and flow cytometry showed lower proliferation of astrocytes after co-culturing with the exosomes transfected with the miR-145-5p mimic. This study finds that miR-145-5p was found to be a negative regulator of astrocyte proliferation, and that its downregulation promotes smad3 activity and thus astrocyte proliferation.
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http://dx.doi.org/10.1007/s11064-021-03446-3DOI Listing
October 2021

Long term follow-up of a phase II study of cladribine with concurrent rituximab with hairy cell leukemia variant.

Blood Adv 2021 Oct 4. Epub 2021 Oct 4.

National Institutes of Health, Bethesda, Maryland, United States.

Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concurrent with cladribine (CDAR) improves response rate, but long-term outcomes are unknown. We report final results of a phase II study of CDAR for patients with HCLv. Twenty patients with 0-1 prior courses of cladribine and/or rituximab, including 8 previously untreated, received cladribine 0.15 mg/kg days 1-5 with 8 weekly rituximab doses 375 mg/m2. Patients received a 2nd rituximab course ≥6 months after cladribine, if/when minimal residual disease (MRD) was detected in blood. The complete remission (CR) rate from CDAR was 95%, 95% confidence interval (95%CI) 75-100%. Sixteen of 20 patients (80%, 95% CI: 56-94%) became MRD-negative by bone marrow at 6 months. The median duration of MRD-negative CR was 70.1 months and 7 of 16 are still MRD-negative up to 120 months. With median follow-up of 69.7 months, 11 patients received delayed rituximab and the 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 73.9%, respectively. Five patients with TP53 mutations had shorter PFS (median: 36.4 months vs unreached, p=0.0024) and OS (median: 52.4 months vs unreached, p=0.032). MRD-negative CR at 6 months was significantly associated with longer PFS (unreached vs 17.4 months, p<0.0001) and OS (unreached vs 38.2 months, p<0.0001). Lack of MRD in blood at 6 months was also predictive of longer PFS and OS (p<0.0001). After progression following CDAR, median OS was 29.7 months. CDAR is effective in HCLv with better outcome in patients who achieved MRD-negative CR.
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http://dx.doi.org/10.1182/bloodadvances.2021005039DOI Listing
October 2021

Stimulus-Specific Expression, Selective Generation and Novel Function of Grass Carp () IL-12 Isoforms: New Insights Into the Heterodimeric Cytokines in Teleosts.

Front Immunol 2021 16;12:734535. Epub 2021 Sep 16.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Interleukin-12 (IL-12) is a heterodimeric cytokine composed of a p35 subunit specific to IL-12 and a p40 subunit shared with IL-23. In this study, we unveiled the existence of two paralogues in grass carp (named and ). Notably, and displayed distinct inducible expression patterns, as poly I:C merely induced the gene expression of but not , while recombinant grass carp interferon-gamma (rgcIfn-γ) only enhanced the transcription of but not . Moreover, the signaling mechanisms responsible for the inducible expression of and mRNA were elucidated. Because of the existence of three grass carp genes ( and ) and two paralogues, six gcIl-12 isoforms were predicted by 3D modeling. Results showed that gcp40a and gcp40b but not gcp40c had the potential for forming heterodimers with both gcp35 paralogues the disulfide bonds. Non-reducing electrophoresis experiments further disclosed that only gcp40b but not gcp40a or gcp40c could form heterodimers with gcp35 to produce secretory heterodimeric gcp35a/gcp40b (gcIl-12AB) and gcp35b/gcp40b (gcIl-12BB), which prompted us to prepare their recombinant proteins. These two recombinant proteins exhibited their extensive regulation on Ifn-γ production in various immune cells. Intriguingly, both gcIl-12 isoforms significantly enhanced the transcription of and in lymphocytes, and their regulation on expression was mediated by Stat3/Rorγt signaling, supporting the potential of gcIl-12 isoforms for inducing Th17-like responses. Additionally, stimulatory effects of gcIl-12 isoforms on and expression were attenuated by gcTgf-β1 suppressing the activation of Stat3 signaling, implying that their signaling could be manipulated. In brief, our works provide new insights into the inducible expression pattern, heterodimeric generation and functional novelty of Il-12 isoforms in teleosts.
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http://dx.doi.org/10.3389/fimmu.2021.734535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481787PMC
September 2021

N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties.

Eur J Med Chem 2021 Sep 24;226:113859. Epub 2021 Sep 24.

Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. Electronic address:

Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.
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http://dx.doi.org/10.1016/j.ejmech.2021.113859DOI Listing
September 2021

IL-30 ameliorates imiquimod and K14-VEGF induced psoriasis-like disease by inhibiting both innate and adaptive immunity disorders.

Biochem Biophys Res Commun 2021 Nov 21;579:97-104. Epub 2021 Sep 21.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. Electronic address:

Psoriasis is a severe skin disease with significant physical and psychological health consequences. As a typical type of immune disease, both innate and adaptive immunity disorders play key roles in the development of psoriasis. Interleukin (IL)-30 was thought as a natural antagonist of gp130-mediated signaling that affects T helper type 1 and 17 cell polarization by inhibiting IL-6 and IL-27 signaling pathways. Here, we found that, in vitro, IL-30 reduced cytokine levels of HaCaT keratinocytes and dendritic cells (DCs), weakened the maturationS of DCs, inhibited DC-mediated T cell proliferation, and blocked the activation of nuclear factor-κB. In vivo, IL-30 inhibited the development of skin disease in two animal models: Krt14-Vegfa and imiquimod (IMQ)-induced psoriasis-like skin disease. Thus, IL-30 may be useful as a therapeutic agent for controlling psoriasis.
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http://dx.doi.org/10.1016/j.bbrc.2021.09.042DOI Listing
November 2021

Cholesterol biosynthesis inhibitor RO 48‑8071 inhibits pancreatic ductal adenocarcinoma cell viability by deactivating the JNK and ERK/MAPK signaling pathway.

Mol Med Rep 2021 Dec 30;24(6). Epub 2021 Sep 30.

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

The morbidity and mortality of pancreatic cancer have been continuously increasing, causing seven deaths per 100,000 individuals/year. At present, effective therapies are severely lacking, thus, highlighting the importance of developing novel therapeutic approaches. The present study aimed to investigate the inhibitory roles of the 2,3‑oxidosqualene cyclase inhibitor, RO 48‑8071 (RO), on pancreatic ductal adenocarcinoma. RO was used to treat the pancreatic cancer cell line (PANC‑1) to examine the effects of RO on cell viability, as well as to determine its potential molecular mechanism. Moreover, experiments in a xenograft model of subcutaneous tumors generated by injecting PANC‑1 cells hypodermically into nude mice were performed to observe the inhibition of RO on tumor growth. It was found that RO inhibited PANC‑1 cell viability when treatment was given for 24, 48 and 72 h. The study demonstrated that RO markedly inhibited subcutaneous tumor growth in nude mice. Further studies revealed that RO could induce cell cycle arrest in the G1 phase by regulating p27, cyclin B1 and cyclin E expression to inhibit PANC‑1 cell viability. Moreover, RO inactivated the JNK and ERK MAPK signaling pathway by decreasing the phosphorylation levels of JNK and ERK. Collectively, the present study demonstrated that RO served anti‑pancreatic cancer roles and , which may provide new ideas and facilitate the development of novel treatment options for pancreatic cancer.
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http://dx.doi.org/10.3892/mmr.2021.12468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503744PMC
December 2021

Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE.

Nat Commun 2021 09 28;12(1):5690. Epub 2021 Sep 28.

Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

SLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown. In this work, we report the cryo-EM 3.4 Å structure of the OF conformation of NDCBE (SLC4A8), which shares transport properties with both AE1 and NBCe1 by mediating the electroneutral exchange of sodium-carbonate with chloride. This structure features a fully resolved extracellular loop 3 and well-defined densities corresponding to sodium and carbonate ions in the tentative substrate binding pocket. Further, we combine computational modeling with functional studies to unravel the molecular determinants involved in NDCBE and SLC4 transport.
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http://dx.doi.org/10.1038/s41467-021-25998-2DOI Listing
September 2021

Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants.

Nat Commun 2021 09 27;12(1):5652. Epub 2021 Sep 27.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China.

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.
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http://dx.doi.org/10.1038/s41467-021-25997-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476643PMC
September 2021

Efficacy of non-pharmacological interventions in patients with overactive bladder: A protocol for systematic review and network meta-analysis.

Nurs Open 2021 Sep 25. Epub 2021 Sep 25.

The Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Some meta-analyses have proved the superiority of non-pharmacological interventions in overactive bladder (OAB), but the best choice is still controversial.

Aim: To assess the most effective interventions in female with OAB.

Methods: Studies for relevant randomized controlled trials which compare different kinds of non-pharmacological interventions in females with OAB will be retrieved from 8 databases including PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine disc, from inception to 1 January 2021. After screening titles and abstracts, detailed data including participates, interventions and outcomes will be extracted according to the eligible criteria. Then, Cochrane risk-of-bias tool will be used to assess the quality of the literature. The pairwise meta-analysis will be conducted by STATA. Network meta-analysis will be performed to compare and rank the effects of different non-pharmacological interventions, in terms of alleviation of symptoms, by OpenBUGS, R and STATA.

Results: This network meta-analysis will present the best available evidence about non-pharmacological interventions for OAB to both relieve symptoms and improve life quality.
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http://dx.doi.org/10.1002/nop2.1078DOI Listing
September 2021

Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.

Cancer Med 2021 Sep 25. Epub 2021 Sep 25.

Zhenjiang Clinical Research Center of Hematology, Jiangsu, China.

The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.
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http://dx.doi.org/10.1002/cam4.4284DOI Listing
September 2021

Factors associated with exclusive breastfeeding practice among mothers in nine community health centres in Nanning city, China: a cross-sectional study.

Int Breastfeed J 2021 09 23;16(1):71. Epub 2021 Sep 23.

Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, China.

Background: The prevalence of exclusive breastfeeding (EBF) is suboptimal in China. There is limited evidence of effective interventions to increase EBF in China. Therefore, it is urgent to explore the potential factors that may be effective in promoting exclusive breastfeeding. Previous studies have mainly focused on socio-demographic factors and the Han ethnic group. This study explores more modifiable influencing factors of EBF in the Guangxi Zhuang Autonomous Region of China.

Methods: The cross-sectional data used in this study were collected to provide baseline information on EBF prevalence for a breastfeeding promotion project. A total of 494 mothers of infants aged 0-5 months were recruited from nine community health centres in Nanning, China, in October 2019. Data were collected through face-to-face interviews using structured questionnaires. Infant feeding was measured by 24-h recall. The Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form was used to examine the maternal breastfeeding self-efficacy. Univariate and multivariate logistic regressions were used to examine the factors associated with EBF practices.

Results: In the present study, the prevalence of exclusive breastfeeding was 37.0%. Higher breastfeeding self-efficacy scores (adjusted odds ratio [AOR] 1.93; 95% confidence interval [CI] 1.25, 2.98), a college degree or above (AOR 2.15; 95% CI 1.24, 3.71), and early initiation of breastfeeding (AOR 2.06; 95% CI 1.29, 3.29) were positively associated with EBF practice. However, the preparation for infant formula before childbirth (AOR 0.30; 95% CI 0.17, 0.52) and premature birth (AOR 0.30; 95% CI 0.10, 0.87) were negatively associated with EBF practice.

Conclusions: Exclusive breastfeeding practice was suboptimal and associated with various factors in the study area. The prevalence of EBF was positively associated with higher breastfeeding self-efficacy, education level of mothers, and early initiation of breastfeeding, whereas premature birth and preparation for infant formula before childbirth were barriers to exclusive breastfeeding. Future intervention projects should target mothers with premature babies, lower levels of education, and breastfeeding self-efficacy. Breastfeeding-friendly practices, such as the early initiation of breastfeeding and regulations on breastmilk substitutes, should also be encouraged.
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http://dx.doi.org/10.1186/s13006-021-00416-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461910PMC
September 2021

A complete mitochondrial genome for fragrant Chinese rosewood (Dalbergia odorifera, Fabaceae) with comparative analyses of genome structure and intergenomic sequence transfers.

BMC Genomics 2021 Sep 18;22(1):672. Epub 2021 Sep 18.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.

Background: Dalbergia odorifera is an economically and culturally important species in the Fabaceae because of the high-quality lumber and traditional Chinese medicines made from this plant, however, overexploitation has increased the scarcity of D. odorifera. Given the rarity and the multiple uses of this species, it is important to expand the genomic resources for utilizing in applications such as tracking illegal logging, determining effective population size of wild stands, delineating pedigrees in marker assisted breeding programs, and resolving gene networks in functional genomics studies. Even the nuclear and chloroplast genomes have been published for D. odorifera, the complete mitochondrial genome has not been assembled or assessed for sequence transfer to other genomic compartments until now. Such work is essential in understanding structural and functional genome evolution in a lineage (Fabaceae) with frequent intergenomic sequence transfers.

Results: We integrated Illumina short-reads and PacBio CLR long-reads to assemble and annotate the complete mitochondrial genome of D. odorifera. The mitochondrial genome was organized as a single circular structure of 435 Kb in length containing 33 protein coding genes, 4 rRNA and 17 tRNA genes. Nearly 4.0% (17,386 bp) of the genome was annotated as repetitive DNA. From the sequence transfer analysis, it was found that 114 Kb of DNA originating from the mitochondrial genome has been transferred to the nuclear genome, with most of the transfer events having taken place relatively recently. The high frequency of sequence transfers from the mitochondria to the nuclear genome was similar to that of sequence transfer from the chloroplast to the nuclear genome.

Conclusion: For the first-time, the complete mitochondrial genome of D. odorifera was assembled in this study, which will provide a baseline resource in understanding genomic evolution in the highly specious Fabaceae. In particular, the assessment of intergenomic sequence transfer suggests that transfers have been common and recent indicating a possible role in environmental adaptation as has been found in other lineages. The high turnover rate of genomic colinearly and large differences in mitochondrial genome size found in the comparative analyses herein providing evidence for the rapid evolution of mitochondrial genome structure compared to chloroplasts in Faboideae. While phylogenetic analyses using functional genes indicate that mitochondrial genes are very slowly evolving compared to chloroplast genes.
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http://dx.doi.org/10.1186/s12864-021-07967-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449883PMC
September 2021

Structure of human cytomegalovirus virion reveals host tRNA binding to capsid-associated tegument protein pp150.

Nat Commun 2021 09 17;12(1):5513. Epub 2021 Sep 17.

California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Under the Baltimore nucleic acid-based virus classification scheme, the herpesvirus human cytomegalovirus (HCMV) is a Class I virus, meaning that it contains a double-stranded DNA genome-and no RNA. Here, we report sub-particle cryoEM reconstructions of HCMV virions at 2.9 Å resolution revealing structures resembling non-coding transfer RNAs (tRNAs) associated with the virion's capsid-bound tegument protein, pp150. Through deep sequencing, we show that these RNA sequences match human tRNAs, and we built atomic models using the most abundant tRNA species. Based on our models, tRNA recruitment is mediated by the electrostatic interactions between tRNA phosphate groups and the helix-loop-helix motif of HCMV pp150. The specificity of these interactions may explain the absence of such tRNA densities in murine cytomegalovirus and other human herpesviruses.
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http://dx.doi.org/10.1038/s41467-021-25791-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448752PMC
September 2021

Intravital Microscopy Imaging of Invariant Natural Killer T-Cell Dynamics in the Liver Using CXCR6-eGFP Transgenic Mice.

Methods Mol Biol 2021 ;2388:149-156

School of Life Science, Anhui Medical University, Hefei, China.

The immune response in the liver is a highly dynamic process involving the recruitment of many types of immune cells. As a powerful imaging technique, intravital microscopy has been widely used for real-time observation and quantification of cell movements in living animals. Here we describe the use of an in vivo half-dissociated preparation method combined with intravital confocal microscopy to observe the dynamic activities of invariant natural killer T cells in the liver of CXCR6 transgenic mice. We believe that this method will enable researchers to explore the dynamics of many other types of immune cells in the liver.
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http://dx.doi.org/10.1007/978-1-0716-1775-5_14DOI Listing
January 2021

Does longer storage of blastocysts with equal grades in a cryopreserved state affect the perinatal outcomes?

Cryobiology 2021 Sep 11. Epub 2021 Sep 11.

Reproductive Medicine Center, Maternal and Child Health Hospital, Obstetrics and Gynecology Hospital of Guangxi Zhuang Autonomous Region, Nanning, PR China.

Aim: Although mammalian embryos could be preserved in liquid nitrogen for thousands of years in theoretical models, the viability of cryopreserved blastocyst with varying grades remains to be speculated. In this study, we aimed to determine whether the longer storage time of blastocysts with equal grades could negatively affect the perinatal outcomes.

Materials And Methods: Single vitrified-warmed blastocyst was divided into four grades (AA, AB/BA, BB, BC/CB) according to the blastocyst score when freezing, and each grade of blastocyst was categorized into four storage duration categories: 28 days-1 year, 1-3 years, 3-5 years, and ≥5 years. Then the perinatal outcomes with different storage time were analyzed.

Results: Our results revealed that for blastocysts with the same grade, the length of storage time had no statistical effect on blastocyst survival rate, clinical pregnancy/implantation rate, live birth rate, and abortion rate. In addition, more advanced developmental blastocyst could obtain better pregnancy outcomes regardless of the cryopreservation length. Similar neonatal outcomes were obtained over time.

Conclusions: Cryopreservation time could not negatively affect the perinatal outcomes of blastocysts with equal grades. Efficient blastocyst cryopreservation technology by vitrification can help older women obtain high-quality embryos at a young age.
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http://dx.doi.org/10.1016/j.cryobiol.2021.09.003DOI Listing
September 2021

Glial IL-33 signaling through an ST2-to-CXCL12 pathway in the spinal cord contributes to morphine-induced hyperalgesia and tolerance.

Sci Signal 2021 Sep 7;14(699):eabe3773. Epub 2021 Sep 7.

Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.

[Figure: see text].
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http://dx.doi.org/10.1126/scisignal.abe3773DOI Listing
September 2021

Long noncoding RNA SATB1-AS1 contributes to the chemotherapy resistance through the microRNA-580/ 2'-5'-oligoadenylate synthetase 2 axis in acute myeloid leukemia.

Bioengineered 2021 12;12(1):6403-6417

Department of Hematology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.

Acute myeloid leukemia (AML) represents a hematopoietic cancer with an invasive property. Chemoresistance blunts the therapeutic effect of chemotherapeutics in AML. Long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in AML. Transcriptome sequencing in the current study was applied to clarify the differentially expressed lncRNAs between peripheral blood mononuclear cells of AML and normal samples. The expression of special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) and 2'-5'-oligoadenylate synthetase 2 (OAS2) in AML patients was evaluated by qRT-PCR. The relationships among SATB1-AS1, microRNA-580 (miR-580) and OAS2 were investigated by dual-luciferase reporter assay. We observed that SATB1-AS1 and OAS2 were upregulated, while miR-580 was downregulated in AML patients. SATB1-AS1 depletion suppressed proliferation, and enhanced apoptosis and sensitivity of AML cells. Additionally, SATB1-AS1 promoted the expression of OAS2 by acting as a molecular sponge of miR-580 in AML. miR-580 downregulation, OAS2 overexpression and a selective glycogen synthase kinase (GSK)-3β inhibitor AR-A014418 abolished the effects of SATB1-AS1 deletion on the chemosensitivity of AML cells. In conclusion, SATB1-AS1 knockdown promotes the sensitivity of AML cells by upregulating miR-580 and downregulating OAS2 through the GSK3β/β-catenin pathway, providing new insights into the function of SATB1-AS1 as a miRNA sponge in AML.
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http://dx.doi.org/10.1080/21655979.2021.1971508DOI Listing
December 2021

A multicenter study of incidence, risk factors and outcomes of babies with birth asphyxia in Nepal.

BMC Pediatr 2021 09 10;21(1):394. Epub 2021 Sep 10.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Background: Perinatal events which result in compromised oxygen delivery to the fetus can lead to Birth Asphyxia (BA). While the incidence, risk factors and outcomes of BA have been characterized, less is known in low resource settings.

Aim: To determine the incidence of Birth Asphyxia (BA) in Nepal and to evaluate associated risk factors and outcomes of this condition.

Methods: A nested observational study was conducted in 12 hospitals of Nepal for a period of 14 months. Babies diagnosed as BA at ≥37 weeks of gestation were identified and demographics were reviewed. Data were analyzed using binary logistic regression followed by multiple logistic regression analysis.

Results: The incidence of BA in this study was 6 per 1000 term livebirths and was higher among women 35 years and above. Predictors for BA were instrumented vaginal delivery (aOR:4.4, 95% CI, 3.1-6.1), fetal distress in labour (aOR:1.9, 95% CI, 1.0-3.6), malposition (aOR:1.8, 95% CI, 1.0-3.0), birth weight less than 2500 g (aOR:2.0, 95% CI, 1.3-2.9), gestational age ≥ 42 weeks (aOR:2.0, 95% CI, 1.3-3.3) and male gender (aOR:1.6, 95% CI, 1.2-2.0). The risk of pre-discharge mortality was 43 times higher in babies with BA (aOR:42.6, 95% CI, 32.2-56.3).

Conclusion: The incidence of Birth asphyxia in Nepal higher than in more resourced setting. A range of obstetric and neonatal risk factors are associated with BA with an associated high risk of pre-discharge mortality. Interventions to improve management and decrease rates of BA could have marked impact on outcomes in low resource settings.
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http://dx.doi.org/10.1186/s12887-021-02858-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431921PMC
September 2021

Stromal composition predicts relapse of early rectal cancer after local resection: several methodological concerns.

Histopathology 2021 Sep 8. Epub 2021 Sep 8.

Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei, People's Republic of China.

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http://dx.doi.org/10.1111/his.14561DOI Listing
September 2021

[Prognosis and Related Factors of Patients with Pathological Complete Response after Neoadjuvant Therapy for Gastric Cancer].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Aug;43(4):571-578

Department of Pancreatic and Gastric Surgical Oncology,Beijing 100021,China.

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(=4.401,95% =2.023-9.574,<0.001)and preoperative therapeutic response as partial response(=40.492,95% =5.366-305.572,<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(=1.809,95% =1.104-2.964,=0.019),gastric cardia-fundus-body tumor(=2.025,95% =1.497-2.739,<0.001),≤15 intraoperative dissected lymph nodes(=1.482,95% =1.059-2.073,=0.022),and postoperative complications(=1.625,95% =1.156-2.285,=0.005)were independent risk factors for prognosis,while pCR(=0.153,95% =0.048-0.484,=0.001)and postoperative adjuvant chemotherapy(=0.589,95% =0.421-0.823,<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13260DOI Listing
August 2021

Arthritis and the role of endogenous glucocorticoids.

Bone Res 2020 Sep 8;8(1):33. Epub 2020 Sep 8.

Bone Research Program, ANZAC Research Institute, The University of Sydney, Camperdown, NSW, Australia.

Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.
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http://dx.doi.org/10.1038/s41413-020-00112-2DOI Listing
September 2020

Hypersensitivity in the lungs is responsible for acute respiratory failure in COVID-19 patients: Case series of patients who received high-dose/short-term methylprednisolone.

Clin Transl Allergy 2021 Aug 27;11(7):e12056. Epub 2021 Aug 27.

Department of Pulmonary and Critical Care Medicine (PCCM) The Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai Guangdong Province China.

Background: COVID-19 is a highly contagious respiratory disease caused by the SARS-CoV-2 virus. Patients with severe disease have a high fatality rate and face a huge medical burden due to the need for invasive mechanical ventilation. Hypoxic respiratory failure is the major cause of death in these patients. There are currently no specific anti-SARS-CoV-2 drugs, and the effect of corticosteroids is still controversial.

Methods: The clinical data of 102 COVID-19 patients, including 27 patients with severe disease, were analyzed. The serum levels of total IgE and anti-SARS-CoV-2 specific IgE were compared in healthy controls and COVID-19 patients, changes in the level of anti-SARS-CoV-2 specific IgE and clinical response to methylprednisolone (MP) treatment were analyzed, and the effect of high-dose/short-term MP therapy for patients with critical illness and respiratory failure was determined.

Results: COVID-19 patients had elevated serum levels of anti-SARS-CoV-2 specific IgE, and patients with severe disease, especially critical illness, had even higher levels. Application of short-term/high-dose MP significantly reduced the level of these IgE antibodies and also blocked the progression of hypoxic respiratory failure. Hypoxic respiratory failure in patients with COVID-19 is related to pulmonary hypersensitivity.

Conclusions: Hypersensitivity in the lungs is responsible for acute respiratory failure in COVID-19 patients. Application of high-dose/short-term MP appears to be an effective life-saving method for COVID-19 patients who have hypoxic respiratory failure.
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http://dx.doi.org/10.1002/clt2.12056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394771PMC
August 2021
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