Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis.

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases. Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019 (COVID-19) infection. COVID-19 causes pulmonary embolisms, thus new therapeutic options are required to target thrombosis, as conventional treatment options are either not effective due to the complexity of the immune-thrombosis pathophysiology. In this review, we discuss regulation of immune response in respiratory diseases especially COVID-19. We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles, which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases. We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways, and thus can be recommended to treat respiratory infectious diseases.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme OXCT1. We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in hepatocellular carcinoma in vivo, we conducted multiplex immunohistochemistry (mIHC) experiments on human HCC specimens. To explore the role of OXCT1 in mouse hepatocellular carcinoma tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4 trimethylation (H3K4me3) level in the Arg1 promoter. In addition, Pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreasing CD8+ T-cell exhaustion and deceleration of tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in HCC patients. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping HCC progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for HCC. Here, we found that ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. And the strategic pharmacological intervention or genetic downregulation of OXCT1 in TAMs enhances the antitumor immunity and decelerated tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs is an effective approach for treating liver cancer.

Highly Stable Solid Contact Calcium Ion-Selective Electrodes: Rapid Ion-Electron Transduction Triggered by Lipophilic Anions Participating in Redox Reactions of CunS Nanoflowers.

Solid contact (SC) calcium ion-selective electrodes (Ca2+-ISEs) have been widely applied in the analysis of water quality and body fluids by virtue of the unique advantages of easy operation and rapid response. However, the potential drift during the long-term stability test hinders their further practical applications. Designing novel redox SC layers with large capacitance and high hydrophobicity is a promising approach to stabilize the potential stability, meanwhile, exploring the transduction mechanism is also of great guiding significance for the precise design of SC layer materials. Herein, flower-like copper sulfide (CunS-50) composed of nanosheets is meticulously designed as the redox SC layer by modification with the surfactant (CTAB). The CunS-50-based Ca2+-ISE (CunS-50/Ca2+-ISE) demonstrates a near-Nernstian slope of 28.23 mV/dec for Ca2+ in a wide activity linear range of 10-7 to 10-1 M, with a low detection limit of 3.16 × 10-8 M. CunS-50/Ca2+-ISE possesses an extremely low potential drift of only 1.23 ± 0.13 µV/h in the long-term potential stability test. Notably, X-ray absorption fine-structure (XAFS) spectra and electrochemical experiments are adopted to elucidate the transduction mechanism that the lipophilic anion (TFPB-) participates in the redox reaction of CunS-50 at the solid-solid interface of ion-selective membrane (ISM) and redox inorganic SC layer (CunS-50), thereby promoting the generation of free electrons to accelerate ion-electron transduction. This work provides an in-depth comprehension of the transduction mechanism of the potentiometric response and an effective strategy for designing redox materials of ion-electron transduction triggered by lipophilic anions.

Role of Carotid Ultrasonography Combined with Monocyte/HDL Ratio in Internal Carotid Artery Stenosis.

BACKGROUND: Carotid duplex ultrasonography (DUS) is the primary screening tool for carotid artery stenosis, but has low reliability. MHR, which is the ratio of monocytes to high-density lipoprotein cholesterol (HDL-C), can be a marker for the degree and distribution of extracranial and intracranial atherosclerotic stenosis. OBJECTIVE: We determined the diagnostic value of DUS+MHR for internal carotid artery (ICA) stenosis. METHODS: We divided 273 hospitalized patients into non-stenosis (<50%) and ICA stenosis (≥50%) groups based on Digital Subtraction Angiography (DSA). We determined the peak systolic velocity (PSV) in the ICA on DUS, calculated the MHR, and investigated their relationship with ICA stenosis. RESULTS: On DSA, 34.1% (93/273) patients had moderate-to-severe ICA stenosis. DUS and DSA showed low concordance for detecting ICA stenosis (kappa = 0.390). With increasing age, the incidence of moderate-to-severe ICA stenosis increased. PSV, monocyte count, and MHR were significantly greater in the stenosis group than in the non-stenosis group (P < 0.001), while the HDL-C level was significantly lower (P = 0.001). PSV (OR: 1.020, 95% CI: 1.011-1.029, P < 0.001) and MHR (OR: 5.662, 95% CI: 1.945-16.482, P = 0.002) were independent risk factors for ICA stenosis. The area under the receiver operating characteristic curve of PSV+MHR (0.819) was significantly higher than that of PSV or MHR alone (77.42% sensitivity, P = 0.0207; 73.89% specificity, P = 0.0032). CONCLUSION: The combination of ICA PSV on DUS and MHR is better than PSV alone at identifying ICA stenosis and is well-suited to screen high-risk patients.

The complete chloroplast genome and phylogenetic analysis of Bauhinia glauca subsp. hupehana (Craib) T. C. Chen 1988.

Bauhinia glauca subsp. hupehana (Craib) T. C. Chen 1988, a member of the Leguminosae family, Cercidoideae subfamily, and Bauhinia genus, has a rich history of traditional usage in Chinese medicine. Renowned for its analgesic properties, it is commonly employed for managing inflammation and pain. This study aimed to sequence the complete chloroplast genome of B. glauca subsp. hupehana using Illumina paired-end sequencing data. The chloroplast genome spans 156,967 bp and consists of four main regions: the large single-copy (LSC) region (89,185 bp), the small single-copy (SSC) region (19,146 bp), and a pair of inverted repeats (IRs) (24,318 bp). The overall GC content of the chloroplast genome is 36.19%, with specific values of 33.99%, 29.79%, and 42.76% for the LSC, SSC, and IR regions, respectively. A total of 128 genes were annotated in the chloroplast genome, including 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis revealed that B. glauca subsp. hupehana is closely related to Bauhinia racemose, indicating a sister taxon relationship between the two species. This study significantly contributes to the chloroplast genomic resource for Bauhinia, laying the groundwork for future phylogenetic investigations within the genus.

Chronic lead exposure prolongs the immature stages of brown-legged grain mite, Aleuroglyphus ovatus, in a long-term population study.

An important aspect of environmental pollution, lead contamination is a widespread problem in several ecosystems. The present study aimed to evaluate the potential effects of low concentration lead stress on the development and reproduction of Aleuroglyphus ovatus. They were fed with artificial diet containing four different concentrations of lead (12.5, 25, 50, and 100 mg/kg). The results showed that there were both accelerating effect of lead (at low concentrations), as well as retarding effects (at high concentrations) on the development of the mite, and lead stress significantly prolonged the immature stages of A. ovatus and this inhibitory effect was greater with greater lead concentrations. The immature stages in the L group were shorter than those in the S group. In the S and L groups, the oviposition periods were significantly longer in the treatments with lower lead concentrations than in the control, while they were significantly shorter in those treatments of higher lead concentrations. Age-specific survival rate (lx) started to decline earlier in the S group, whereas there were no differences between the L group and CK. Age-specific fecundity rate (mx) peaked earlier in the S group than in CK, while mx peaked later in L1 and L2 than in CK. The rm value and net reproduction rate (R0) of treated A. ovatus decreased with increasing lead concentrations. Lower lead concentrations could promote population expansion while higher concentrations could inhibit population size. These results confirmed the developmental effect of lead stress on A. ovatus, highlighting that heavy metal contamination has negative effects on organisms in their natural environment.

The 100 most cited papers in nasopharyngeal carcinoma between 2000 and 2019: a bibliometric study.

Background: To identify the 100 most-cited papers that have contributed to the understanding and treatment of nasopharyngeal carcinoma (NPC). Methods: We searched the NPC-related papers between 2000 and 2019 using the Web of Science database on October 12, 2022. Papers were identified in descending order according to the number of citations. The top 100 papers were analyzed. Results: These 100 most cited papers on NPC have been cited for a total of 35,273 times, with a median number of citations of 281 times. There were 84 research papers and 16 review papers. The Journal of Clinical Oncology (n=17), International Journal of Radiation Oncology Biology Physics (n=13), and Cancer Research (n=9) published the most papers. Cancer Epidemiology Biomarkers & Prevention, Lancet, Cancer Cell, Molecular Cancer, and the New England Journal of Medicine had the largest average citations per paper. China contributed the most papers (n=71), followed by USA (n=13), Singapore (n=4) and, France (n=4). There were 55 clinical research papers and 29 laboratory research papers. Intensity-modulated radiation therapy technology (n=13), concurrent chemoradiotherapy (n=9), and neoadjuvant chemoradiotherapy (n=5) were the top three research topics. Epstein-Barr virus-related genes (n=9) and noncoding RNA (n=8) were the research domains in laboratory research papers. The top three contributors were Jun Ma (n=9), Anthony T C Chan (n=8), and Anne Wing-Mui Lee (n=6). Conclusions: This study provides an overview of the major areas of interest in the field of NPC with bibliometric analyses. This analysis recognizes some important contributions in the field of NPC and stimulates future investigations in the scientific community.

Comparative Analysis of Codon Usage Patterns in Nuclear and Chloroplast Genome of Dalbergia (Fabaceae).

The Dalbergia plants are widely distributed across more than 130 tropical and subtropical countries and have significant economic and medicinal value. Codon usage bias (CUB) is a critical feature for studying gene function and evolution, which can provide a better understanding of biological gene regulation. In this study, we comprehensively analyzed the CUB patterns of the nuclear genome, chloroplast genome, and gene expression, as well as systematic evolution of Dalbergia species. Our results showed that the synonymous and optimal codons in the coding regions of both nuclear and chloroplast genome of Dalbergia preferred ending with A/U at the third codon base. Natural selection was the primary factor affecting the CUB features. Furthermore, in highly expressed genes of Dalbergia odorifera, we found that genes with stronger CUB exhibited higher expression levels, and these highly expressed genes tended to favor the use of G/C-ending codons. In addition, the branching patterns of the protein-coding sequences and the chloroplast genome sequences were very similar in the systematic tree, and different with the cluster from the CUB of the chloroplast genome. This study highlights the CUB patterns and features of Dalbergia species in different genomes, explores the correlation between CUB preferences and gene expression, and further investigates the systematic evolution of Dalbergia, providing new insights into codon biology and the evolution of Dalbergia plants.

Association of chronic kidney disease with all-cause mortality in patients hospitalized for atrial fibrillation and impact of clinical and socioeconomic factors on this association.

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often co-occur, and many of the same clinical factors and indicators of socioeconomic status (SES) are associated with both diseases. The effect of the estimated glomerular filtration rate (eGFR) on all-cause mortality in AF patients and the impact of SES on this relationship are uncertain. Materials and methods: This retrospective study examined 968 patients who were admitted for AF. Patients were divided into four groups based on eGFR at admission: eGFR-0 (normal eGFR) to eGFR-3 (severely decreased eGFR). The primary outcome was all-cause mortality. Cox regression analysis was used to identify the effect of eGFR on mortality, and subgroup analyses to determine the impact of confounding factors. Results: A total of 337/968 patients (34.8%) died during follow-up. The average age was 73.70 ± 10.27 years and there were 522 males (53.9%). More than 39% of these patients had CKD (eGFR < 60 mL/min/1.73 m2), 319 patients with moderately decreased eGFR and 67 with severely decreased eGFR. After multivariate adjustment and relative to the eGFR-0 group, the risk for all-cause death was greater in the eGFR-2 group (HR = 2.416, 95% CI = 1.366-4.272, p = 0.002) and the eGFR-3 group (HR = 4.752, 95% CI = 2.443-9.242, p < 0.00001), but not in the eGFR-1 group (p > 0.05). Subgroup analysis showed that moderately to severely decreased eGFR only had a significant effect on all-cause death in patients with low SES. Conclusion: Moderately to severely decreased eGFR in AF patients was independently associated with increased risk of all-cause mortality, especially in those with lower SES.

Distribution Pattern of N6-Methyladenine DNA Modification in the Seashore Paspalum (Paspalum vaginatum) Genome.

N6-methyladenine (6mA) DNA modification has been detected in several eukaryotic organisms, in some of them, it plays important role in the regulation process of stress-resistance response. However, the genome-wide distribution patterns and potential functions of 6mA DNA modification in halophyte Seashore paspalum (Paspalum vaginatum) remain largely unknown. Here, we examined the 6mA landscape in the P. vaginatum genome by adopting single molecule real-time sequencing technology and found that 6mA modification sites were broadly distributed across the P. vaginatum genome. We demonstrated distinct 6mA methylation levels and 6mA distribution patterns in different types of transcription genes, which hinted at different epigenetic rules. Furthermore, the moderate 6mA density genes in P. vaginatum functionally correlated with stress resistance, which also maintained a higher transcriptional level. On the other hand, a specific 6mA distribution pattern in the gene body and near TSS was observed in gene groups with higher RNA expression, which maybe implied some kind of regularity between 6mA site distribution and the protein coding genes transcription was possible. Our study provides new insights into the association between 6mA methylation and gene expression, which may also contribute to key agronomic traits in P. vaginatum.

[Knot-free suture and frenulum positioning combined with application positioning using a disposable circumcision suture device in circumcision].

OBJECTIVE: To explore the effect of knot-free suture and frenulum positioning combined with application positioning (KFS-FP + AP) in circumcision using a disposable circumcision suture device. METHODS: We retrospectively analyzed the clinical data on 160 cases of circumcision for phimosis or redundant prepuce by KFS-FP + AP (the observation group, n = 80) or by routine circumcision (the control group, n = 80) with a disposable circumcision suture device from February 2021 to December 2021. We recorded the operation time, incidence of frenulum breve, incidence of frenulum dislocation, and Visual Analog Scale (VAS) scores at 6 hours after surgery, and compared them between the two groups of patients. RESULTS: The operation time was longer in the observation than in the control group (8.00 ï¼»8.00, 9.00ï¼½ min vs 5.00 ï¼»5.00, 5.00ï¼½ min), and the incidence rates of frenulum breve (0 vs 8.75%, P < 0.05) and frenulum dislocation (0 vs 7.5%, P < 0.05) significantly lower in the former than in the latter group. There were no statistically significant difference in the VAS scores between the observation and the control groups (2.60 ï¼»2.00, 3.00ï¼½ vs 2.55 ï¼»2.00, 3.00ï¼½, P > 0.05). CONCLUSION: KFS-FP + AP with a disposable circumcision suture device is a safe and effective method of circumcision, with high satisfaction of the patients and worthy of clinical promotion.

[Diagnosis and treatment of rectal injury during laparoscopic radical prostatectomy: Analysis of 7 cases].

OBJECTIVE: To explore the risk factors and management principles of rectal injury during laparoscopic radical prostatectomy (LRP). METHODS: We retrospectively analyzed the clinical data on 7 cases of LRP complicated with rectal injury and treated in Huzhou Central Hospital from January 2010 to June 2021. Four of the 7 PCa patients were found with complete rectal rupture during LRP, of whom 2 were treated by laparoscopic rectal repair (LRR) and the other 2 by LRR + colostomy during surgery. Another case of rectal muscle injury also underwent LRR. Two cases of delayed rectal rupture were observed postoperatively and treated by colostomy + transrectal repair in the second-stage operation. RESULTS: The rectal injuries were found in the apex of the prostate in all the 7 cases, pathologically staged as pT2b��pT3b and with Gleason scores of 7��10. Postoperative follow-up lasted 2 to 18 months, during which the 5 cases of intraoperative rectal repair recovered well without complications, and of the 2 cases of postoperative rectal repair, 1 made a good recovery and the other 1 developed rectourethral fistula. CONCLUSION: Rectal injury during radical prostatectomy tends to occur in the apex of the prostate and can be effectively managed by laparoscopic repair. Meanwhile, attention should be paid to the postoperative complication of rectourethral fistula.

Targeting Extracellular Cyclophilin A via an Albumin-Binding Cyclosporine A Analogue.

An albumin-binding CsA analogue 4MCsA was achieved by attachment of a thiol-reactive maleimide group at the side-chain of P4 position of CsA derivative. 4MCsA was semi-synthesized from CsA, and the cell-impermeability of albumin-4MCsA was detected by mass spectrometry and a competitive flow cytometry. 4MCsA exhibits inhibition of chemotaxis activity and inflammation by targeting extracellular CypA without immunosuppressive effect and cellular toxicity. These combined results suggested that 4MCsA can be restricted extracellularly through covalently binding to Cys34 of albumin with its maleimide group, and regulate the functions of cyclophilin A extracellularly.

Sex-Specific Differences in the Physiological and Biochemical Performance of Arbuscular Mycorrhizal Fungi-Inoculated Mulberry Clones Under Salinity Stress.

Arbuscular mycorrhizal fungi (AMF) are often considered bioameliorators. AMF can promote plant growth under various stressful conditions; however, differences between male and female clones in mycorrhizal strategies that protect plants from the detrimental effects of salinity are not well studied. In this study, we aimed to examine the interactive effects of salinity and AMF on the growth, photosynthetic traits, nutrient uptake, and biochemical responses of Morus alba males and females. In a factorial setup, male and female M. alba clones were subjected to three salinity regimes (0, 50, and 200 mM NaCl) and planted in soil with or without Funneliformis mosseae inoculation. The results showed that NaCl alone conferred negative effects on the growth, salinity tolerance, photosynthetic performance, and shoot and root ionic ratios (K+/Na+, Ca2+/Na+, and Mg2+/Na+) in both sexes; in contrast, mycorrhizal inoculation mitigated the detrimental effects of salinity. Furthermore, the mycorrhizal effects were closely correlated with Mn2+, proline, and N concentrations. Females benefited more from AMF inoculation as shown by the enhancements in their biomass accumulation, and N, proline, K+, Mg2+, Fe2+, Zn2+, and Mn2+ concentrations than males with mycorrhizal inoculation under saline conditions. In comparison, male plants inoculated with AMF showed improvements in biomass allocated to the roots, P, and peroxidase concentrations under saline conditions. These sex-specific differences suggest that male and female mulberry clones adopted different mycorrhizal strategies when growing under saline conditions. Overall, our results provide insight into the sex-specific difference in the performance of AMF-associated mulberry clones, suggesting that female mulberry could be more suitable for vegetation remediation than the male one, due to its higher salinity tolerance.

[Pollution and Irrigation Applicability of Surface Water from Wet, Normal, and Dry Periods in the Huixian Karst Wetland, China].

To reveal the hydrochemical characteristics of karst wetland located in a subtropical area and at lower elevations in China, 27 surface water samples were collected during three periods (wet, normal, and dry) in the Huixian karst wetland to investigate the distributions, pollution, and irrigation application of 12 inorganic ions and 10 heavy metals. Based on their concentrations, the Nemerow index and the four evaluation systems of the sodium adsorption ratio (SAR), sodium concentration (SC), permeability index (PI), and residual sodium carbonate (RSC) were applied to evaluate the pollution characteristics and irrigation application. It was found that the water type in this area was Ca2+-HCO3- and weakly alkaline. Regarding the 12 inorganic ions and 10 heavy metals, NH4+ exceeded the Chinese standards for drinking water with an exceedance rate of 25.93%, and the exceedance rates of Al, Mn, and Hg were 11.11%, 44.44%, and 37.04%, respectively. The spatiotemporal scaling effect on inorganic ions was lower than that of heavy metals, and the distributions of the inorganic ions and heavy metals were in the order of wet period > normal period > dry period. However, the surface water quality in the Huixian karst wetland was generally well-protected based on the pollution assessment. The Nemerow index ranged from 0.75 to 2.69, which recognized the main pollution contributors as NH4+, Mn, Al, and Hg with the contamination grade from slight pollution to moderate pollution, especially in the core area during the wet period. According to the limits of standards for irrigation water quality and environmental quality for surface water, as well as the evaluation results of the SAR, SC, PI, and RSC, the surface water in the Huixian karst wetland was generally suitable for irrigation, and the water quality in the dry period was better than that in the wet and normal periods. The surface water from site PH1 during the normal period with 19.1 µg·L-1 of Hg and site FH8 during the wet period with 13.7 mg·L-1 of NH4+ were not suitable for agricultural irrigation.

[Major Ionic Characteristics and Factors of Karst Groundwater at Huixian Karst Wetland, China].

To investigate the major ionic chemical characteristics and seasonal variations, 27 groundwater samples were collected from the wet season, flat season, and dry season during 2018-2019 in the Huixian Karst wetland, which is the largest low-altitude karst wetland in China. The single pollution standard index was applied to evaluate the groundwater pollution during different periods, and the major ionic factors of the karst groundwater were analyzed using the statistical analysis method, Gibbs diagram, and ion ratio. The results revealed that the groundwater samples were a weakly alkaline fresh water that were rich in Ca2+ and HCO3-. The average concentrations of the primary ions followed the order of flat season > wet season > dry season; meanwhile, the water quality in the dry season was better than that in the wet and flat seasons. The K+ and NO3- in the karst groundwater were mostly affected by the spatial distributions of the aquifers, and the Mg2+, SO42-, NO2-, NH4+, and TDS were related to the space-season scale. Na+, Ca2+, HCO3-, and Cl- were relatively stable ions in the karst groundwater. The hydrochemical characteristics were primarily determined by carbonate rock dissolution and were found to be the HCO3-Ca type, which accounted for 77.78%, 77.78%, and 88.89% in the wet season, flat season, and dry season, respectively. The karst groundwater was predominantly polluted by SO42-, NO3-, and NO2-; particularly, NO3- exhibited serious pollution points, and SO42- had heavy pollution points in the wet and flat seasons. The chemical composition of the karst groundwater was controlled mostly by water-rock interactions. Ca2+ and HCO3- primarily came from calcite dissolution, and the high concentrations of Mg2+ and SO42- in a few number of points were controlled by dolomite, dolomitic limestone, and pyrite. K+, Na+, SO42-, NO3-, and Cl- partly came from atmospheric precipitation, and Na+ and Cl- partly came from human activities; K+ was related to potash fertilizer, and the main source of NO3- was chemical fertilizer.

Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a / 神经科学通报·英文版

Acid-sensing ion channels (ASICs), the main H

Neutralizing antibodies targeting SARS-CoV-2 spike protein.

SARS-CoV-2 causing the worldwide pandemic has changed people's life in multiple aspects dramatically since it's first identified in Wuhan, China at the end of 2019. While the numbers of infected patients and death toll keep vigorous increasing, curbing the progression of the pandemic is an urgent goal. Efforts have been made to search for prophylactic and therapeutic approaches including neutralizing antibodies development. By reviewing dozens of studies on anti-spike antibodies identification, we concluded that (1) promising therapeutic antibodies are being fished out by various approaches, such as screening of single B cells of convalescent patients, recombinant antibody library and B cells of immunized animals; (2) the epitopes are mainly RBD, but also some non-RBD domains, without the requisite of overlapping with ACE2 binding sites; (3) Neutralizing antibodies are convergent to a few germline genes, including IGHV3-30, IGHV3-53, IGHV3-66, with varying levels of somatic mutations. This review summarizes the progress in neutralizing antibodies development and the germline enrichment of effective antibodies, which will shed light on COVID-19 treatment and vaccine design.

Analysis of the Trends in Publications on Clinical Cancer Research in Mainland China from the Surveillance, Epidemiology, and End Results (SEER) Database: Bibliometric Study.

BACKGROUND: The application of China's big data sector in cancer research is just the beginning. In recent decades, more and more Chinese scholars have used the Surveillance, Epidemiology, and End Results (SEER) database for clinical cancer research. A comprehensive bibliometric study is required to analyze the tendency of Chinese scholars to utilize the SEER database for clinical cancer research and provide a reference for the future of big data analytics. OBJECTIVE: Our study aimed to assess the trend of publications on clinical cancer research in mainland China from the SEER database. METHODS: We performed a PubMed search to identify papers published with data from the SEER database in mainland China until August 31, 2020. RESULTS: A total of 1566 papers utilizing the SEER database that were authored by investigators in mainland China were identified. Over the past years, significant growth in studies based on the SEER database was observed (P<.001). The top 5 research topics were breast cancer (213/1566, 13.6%), followed by colorectal cancer (185/1566, 11.8%), lung cancer (179/1566, 11.4%), gastrointestinal cancer (excluding colorectal cancer; 149/1566, 9.5%), and genital system cancer (93/1566, 5.9%). Approximately 75.2% (1178/1566) of papers were published from the eastern coastal region of China, and Fudan University Shanghai Cancer Center (Shanghai, China) was the most active organization. Overall, 267 journals were analyzed in this study, of which Oncotarget was the most contributing journal (136/267, 50.9%). Of the 1566 papers studied, 585 (37.4%) were published in the second quartile, 489 (31.2%) in the third quartile, 312 (19.9%) in the first quartile, and 80 (5.1%) in the fourth quartile, with 100 (6.4%) having an unknown Journal Citation Reports ranking. CONCLUSIONS: Clinical cancer research based on the SEER database in mainland China underwent constant and rapid growth during recent years. High-quality and comprehensive cancer databases based on Chinese demographic data are urgently needed.

Potent SARS-CoV-2 neutralizing antibodies selected from a human antibody library constructed decades ago

Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.