Pretreatment of shrimp shells with an acidic deep eutectic solvent system for chitin extraction and its enhanced performance as a carrier for immobilized lipase.

Existing methods for chitin extraction usually produce substantial waste, which poses ecological hazards. Natural deep eutectic solvent (NADES) offers a promising one-step pretreatment alternative, replacing the resource-intensive demineralization (DM) and deproteinization (DP) process. Hence, in this study, the influence of various acidic NADES, on achieving a simplified one-step DM and DP in the chitin extraction process was investigated. The study yielded chitin with 87.73 % purity, and microstructural analysis showed that NADES pretreatment minimally affected chitin quality without deacetylation. In addition, chitin extracted using choline chloride-oxalic acid as a carrier displayed excellent performance in the immobilization of Geobacillus thermocatenulatus lipase 2 (GTL2) because of obvious Ca2+ activation effect. This process contributed to enhancement of immobilized enzyme activity. The immobilized GTL2 showed excellent hydrolytic capabilities, with its highest activity reaching 547.80 ± 20.62 U/mg, significantly better than the five commercial lipases that exhibited <40 % of the enzyme activity. Furthermore, the hydrolytic capacity of immobilized GTL2 was notably high for 4-nitrophenyl butyrate, measuring 935.47 ± 51.60 U/mg. This study provided a constructive approach for the one-step pretreatment of shrimp shells with organic acid-based NADES to isolate and purify chitin and its potential application as an immobilized carrier to enhance enzyme activity.

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

BACKGROUND: Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. OBJECTIVE: This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. METHODS: Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. RESULTS: A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. CONCLUSIONS: TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.

Odontoid incidence: a constant cervical anatomical feature evident in standing plain radiographs and supine magnetic resonance images.

OBJECTIVE: To assess whether there is a difference between measurements of odontoid incidence (OI) and other cervical sagittal parameters by X-ray radiography and those by supine magnetic resonance imaging (MRI). METHODS: Standing X-ray and supine MRI images of 42 healthy subjects were retrospectively analyzed. Surgimap software was employed to measure cervical sagittal parameters including OI, odontoid tilt (OT), C2 slope (C2S), C0-2 angle, C2-7 angle, T1 slope (T1S) and T1S-cervical lordosis (CL). Paired samples t-test was applied to determine the difference between parameters measured by standing X-ray and those by supine MRI. In addition, the statistical correlation between the parameters were compared. The prediction of CL was performed and validated using the formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S. RESULTS: Significant correlations and differences were found between cervical sagittal parameters determined by X-ray and those by MRI. OI was verified to be a constant anatomic parameter and the formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S can be used to predict CL in cervical sagittal parameters. CONCLUSIONS: OI is verified as a constant anatomic parameter, demonstrating the necessity of a combined assessment of cervical sagittal balance by using standing X-ray and supine MRI. The formula CL = 0.36 × OI - 0.67 × OT - 0.69 × T1S can be applied to predict CL in cervical sagittal parameters.

Mediating Triple Ions Migration Behavior via a Fluorinated Separator Interface toward Highly Reversible Aqueous Zn Batteries.

Rampant dendrite growth, electrode passivation and severe corrosion originate from the uncontrolled ions migration behavior of Zn2+ , SO4 2- , and H+ , which are largely compromising the aqueous zinc ion batteries (AZIBs) performance. Exploring the ultimate strategy to eliminate all the Zn anode issues is challenging but urgent at present. Herein, a fluorinated separator interface (PVDF@GF) is constructed simply by grafting the polyvinylidene difluoride (PVDF) on the GF surface to realize high-performance AZIBs. Experimental and theoretical studies reveal that the strong interaction between C─F bonds in the PVDF and Zn2+ ions enables evenly redistributed Zn2+ ions concentration at the electrode interface and accelerates the Zn transportation kinetics, leading to homogeneous and fast Zn deposition. Furthermore, the electronegative separator interface can spontaneously repel the SO4 2- and anchor H+ ions to alleviate the passivation and corrosion. Accordingly, the Zn|Zn symmetric cell with PVDF@GF harvests a superior cycling stability of 500 h at 10 mAh cm-2 , and the Zn|VOX full cell delivers 76.8% capacity retention after 1000 cycles at 2 A g-1 . This work offers an all-round solution and provides new insights for the design of advanced separators with ionic sieve function toward stable and reversible Zn metal anode chemistry.

Thymosin α1 modulated the immune landscape of COVID-19 patients revealed by single-cell RNA and TCR sequencing.

BACKGROUND: The Coronavirus disease-19 (COVID-19) pandemic has posed a serious threat to global health. Thymosin α1 (Tα1) was considered to be applied in COVID-19 therapy. However, the data remains limited. METHODS: Participants with or without Tα1 treatment were recruited. Single cell RNA-sequencing (scRNA-seq) and T cell receptor-sequencing (TCR-seq) of the peripheral blood mononuclear cell (PBMC) samples were done to analyze immune features. The differential expression analysis and functional enrichment analysis were performed to explore the mechanism of Tα1 therapy. RESULTS: 33 symptomatic SARS-CoV-2-infected individuals (COV) and 11 healthy controls (HC) were enrolled in this study. The proportion of CD3+ KLRD1+ NKT, TBX21+ CD8+ NKT was observed to increase in COVID-19 patients with Tα1 treatment (COVT) than those without Tα1 (COV) (p = 0.024; p = 0.010). These two clusters were also significantly higher in Health controls with Tα1 treatment (HCT) than those without Tα1 (HC) (p = 0.016; p = 0.031). Besides, a series of genes and pathways related to immune responses were significantly higher enriched in Tα1 groups TBX21+ CD8+ NKT, such as KLRB1, PRF1, natural killer cell-mediated cytotoxicity pathway, chemokine signaling pathway, JAK-STAT signaling pathway. The increased TRBV9-TRBJ1-1 pair existed in both HCs and COVID-19 patients after Tα1 treatment. 1389 common complementarity determining region 3 nucleotides (CDR 3 nt) were found in COV and HC, while 0 CDR 3 nt was common in COVT and HCT. CONCLUSIONS: Tα1 increased CD3+ KLRD1+ NKT, TBX21+ CD8+ NKT cell proportion and stimulated the diversity of TCR clones in COVT and HCT. And Tα1 could regulate the expression of genes associated with NKT activation or cytotoxicity to promote NKT cells. These data support the use of Tα1 in COVID-19 patients.

Lipid alternations in the plasma of COVID-19 patients with various clinical presentations.

Background: COVID-19 is a highly infectious respiratory disease that can manifest in various clinical presentations. Although many studies have reported the lipidomic signature of COVID-19, the molecular changes in asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals remain elusive. Methods: This study combined a comprehensive lipidomic analysis of 220 plasma samples from 166 subjects: 62 healthy controls, 16 asymptomatic infections, and 88 COVID-19 patients. We quantified 732 lipids separately in this cohort. We performed a difference analysis, validated with machine learning models, and also performed GO and KEGG pathway enrichment analysis using differential lipids from different control groups. Results: We found 175 differentially expressed lipids associated with SASR-CoV-2 infection, disease severity, and viral persistence in patients with COVID-19. PC (O-20:1/20:1), PC (O-20:1/20:0), and PC (O-18:0/18:1) better distinguished asymptomatic infected individuals from normal individuals. Furthermore, some patients tested positive for SARS-CoV-2 nucleic acid by RT-PCR but did not become negative for a longer period of time (≥60 days, designated here as long-term nucleic acid test positive, LTNP), whereas other patients became negative for viral nucleic acid in a shorter period of time (≤45 days, designated as short-term nucleic acid test positive, STNP). We have found that TG (14:1/14:1/18:2) and FFA (4:0) were differentially expressed in LTNP and STNP. Conclusion: In summary, the integration of lipid information can help us discover novel biomarkers to identify asymptomatic individuals and further deepen our understanding of the molecular pathogenesis of COVID-19.

Melatonin Improves Turbot Oocyte Meiotic Maturation and Antioxidant Capacity, Inhibits Apoptosis-Related Genes mRNAs In Vitro.

High-quality eggs are essential for the sustainability of commercial aquaculture production. Melatonin is a potent candidate for regulating the growth and maturation of oocytes. Therefore, research on the effect of melatonin on marine fish oocytes in vitro has been conducted. The present study successfully established a culture system of turbot (Scophthalmus maximus) oocytes in vitro and investigated the effect of melatonin on oocyte meiotic maturation, antioxidant capacity, and the expression of apoptosis-related genes. The cultures showed that turbot Scophthalmus maximus late-vitellogenic denuded oocytes, with diameters of 0.5-0.7 mm, had a low spontaneous maturation rate and exhibited a sensitive response to 17α, 20ß-dihydroxyprogesterone (DHP) treatment in vitro. Melatonin increased by four times the rate of oocyte germinal vesicle breakdown (GVBD) in a concentration- and time-dependent manner. The mRNA of melatonin receptor 1 (mtnr1) was significantly upregulated in the oocyte and follicle after treatment with melatonin (4.3 × 10-9 M) for 24 h in vitro, whereas melatonin receptor 2 (mtnr2) and melatonin receptor 3 (mtnr3) remained unchanged. In addition, melatonin significantly increased the activities of catalase, glutathione peroxidase, and superoxide dismutase, as well as the levels of glutathione, while decreasing the levels of malondialdehyde and reactive oxygen species (ROS) levels in turbot oocytes and follicles cultures in vitro. p53, caspase3, and bax mRNAs were significantly downregulated in oocytes and follicles, whereas bcl2 mRNAs were significantly upregulated. In conclusion, the use of turbot late-vitellogenesis oocytes (0.5-0.7 mm) is suitable for establishing a culture system in vitro. Melatonin promotes oocyte meiotic maturation and antioxidative capacity and inhibits apoptosis via the p53-bax-bcl2 and caspase-dependent pathways, which have important potential to improve the maturation and quality of oocytes.

The Significance of Odontoid Incidence in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: Observational study. OBJECTIVE: To analyze the cervical sagittal parameters for standing Digital radiography (DR) and supine Magnetic resonance imaging (MRI), and to further clarify the relationship between odontoid incidence (OI) and cervical spondylotic myelopathy (CSM). METHODS: 52 CSM patients aged 54.46 ± 2.89 years underwent both standing DR and supine MRI scans of cervical spine between November 2021 and November 2022. OI, odontoid tilt (OT), C2 slope (C2S), T1 slope (T1S), C0-2 angle, C2-7 angle (cervical lordosis [CL]), and T1S-CL were measured in both DR and MRI images using Surgimap (Version 2.3.2.1). Pearson correlation and linear regression were used to compare these parameters between the two modalities. RESULTS: Cervical sagittal parameters, including OI, OT, C2S, C0-2 angle, T1S, C2-7 angle (CL) and T1S-CL, showed no significant differences in the measurements between the two modalities. Based on the DR images, OI was related to OT (r = .386, P < .01), C2S (r = .505, P < .01), CL (r = -.412, P < .01), and T1S-CL (r = .320, P < .05), and OI was matched with CL (r2 = .170) and T1S-CL (r2 = .102). Based on MRI images, OI was related to OT (r = .433, P < .01), C2S (r = .516, P < .01), CL (r = -.355, P < .01), and T1S-CL (r = .271, P < .05), and OI matched with C2-7 (r2 = .126) and T1S-CL (r2 = .073). CONCLUSION: OI is an independent parameter related to cervical anatomy and its measurement is unaffected by external factors. In patients with CSM, odontoid parameters may effectively describe the sagittal alignment of the cervical spine on DR and MRI images.

Discovery of [5,5'-bibenzo[d][1,3]dioxol]-6-substituted amine derivatives as potent proprotein convertase subtilisin/kexin type 9 inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hyperlipidemia. In discovery of novel small molecules that interfere PCSK9/LDLR protein-protein interaction (PPI), structural modification was performed based on our previously derived compounds. A series of [5,5'-bibenzo[d][1,3]dioxol]-6-amine analogs were designed and synthesized for the activity evaluation. In the PCSK9/LDLR PPI impairing test, molecules D28 and D29, exhibited remarkable inhibitory potency with IC50 values of 8.30 and 6.70 µM compared with SBC-115337 (17.89 µM), respectively. Molecular docking predicted the binding pattern of compounds D28 and D29 in the LDLR binding site of PCSK9. Hydrophobic interactions play an important role in the binding of aromatic molecular fragments to the pockets in the PCSK9/LDLR binding interface. Further LDLR expression and LDL uptake studies revealed that both D28 and D29 restored LDLR expression on the surface of hepatic HepG2 cells and improved extracellular LDL uptake in the presence of PCSK9. It is significant that molecules D28 and D29 exhibited potential for the treatment of hyperlipidemia in current in vitro investigations. Generally, lead compounds with novel structures were developed in the present study for further design of lipid-lowering molecules by targeting PCSK9/LDLR PPI.

Hepatic transcriptomic analysis reveals that Hif1α/ldha signal is involved in the regulation of hypoxia stress in black rockfish Sebastes schlegelii.

Hypoxia has become a common problem for aquatic organisms due to the interaction of global climate change and human activity. Black rockfish inhabits rocky reefs in waters of Japan, Korea and China, whereas the limited hypoxia tolerance leads to mass mortality and great economic loss. In this study, high-throughput RNA-seq for transcriptomic analysis was used to investigate the hepatic response in black rockfish under hypoxia (critical oxygen tension, Pcrit; loss of equilibrium, LOE) and reoxygenation (recover normal dissolved oxygen 24 h, R24) to explore the mechanisms underlying hypoxia tolerance and adaptation. A total of 573,040,410 clean reads and 299 differentially expressed genes (DEGs) in total were obtained during hypoxia and reoxygenation. GO annotation and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the DEGs are mainly enriched in the biochemical metabolic pathways and HIF-1 signaling pathways. Transcriptomic analysis also identified 18 DEGs associated with HIF-1 signaling pathway (hif1α, tf, epo, hmox, gult1, mknk2, ldha, pfkfb3, hkdc, aldoa) and biological process (hif2α, apoeb, bcl6, mr1, errfi1, slc38a4, igfbp1a, ap4m1) as further validated by quantitative real-time PCR. Moreover, hif1α was positively or negatively correlated with glucose (ldha, pfkfb3, hkdc, aldoa) and lipid (apoeb) metabolism-related genes. The mRNA level of hif1α was significantly up-regulated under acute hypoxia stress and obtained the higher values than hif2α. Meanwhile, hif1α recognized the hypoxia response element located in the promoter of ldha and directly bound to the promoter to transactivate ldha expression. These results indicated that black rockfish may mainly utilize glycolysis to maintain homeostasis, and hif1α facilities hypoxia tolerance by modulating ldha expression.

Hypoxia stress induces hepatic antioxidant activity and apoptosis, but stimulates immune response and immune-related gene expression in black rockfish Sebastes schlegelii.

Dissolved oxygen concentrations both in the open ocean and coast have been declining due to the interaction of global climate change and human activity. Fish have evolved different adaptative strategies to cope with possibly damage induced by hypoxic environments. Black rockfish as important economic fish widely reared in the offshore sea cage, whereas related physiological response subject to hypoxia stress remained unclear. In this study, hepatic anti-oxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), aminotransferase (AST) and alanine aminotransferase (ALT) activities, lipid peroxidation (LPO), malondialdehyde (MDA) and glutathione (GSH) content, immunological parameters and the expression of apoptosis (bax, bcl2, p53, caspase3, xiap) and immune-related genes (c3, il-1ß, ccl25, saa, hap, isg15) of black rockfish were determined during hypoxia and reoxygenation to illustrate the underlying defense response mechanisms. Results showed that hypoxia stress remarkably increased hepatic LPO and MDA content, AST and ALT activity and proportion of pyknotic nucleus. Hepatic SOD, CAT and GSH-Px activity manifested similar results, whereas GSH levels significantly decreased under hypoxia stress. The apoptosis rate of hepatocyte increased during hypoxia stress and reoxygenation. Meanwhile, p53, caspase3, bax and xiap mRNAs and bax/bcl2 rations were significantly up-regulated under hypoxia stress. However, bcl2 mRNA was significantly down-regulated. Interestingly, hypoxia stress significantly increased NBT-positive cell percent, phagocytic index, respiratory burst and ACH50 activity, and lysozyme activity. The mRNA levels of c3, ilß, ccl25, saa, hap and isg15 were significantly up-regulated in the liver, spleen and head-kidney under hypoxia stress. The above parameters recovered to normal status after reoxygenation for 24 h Thus, hypoxia stress impairs hepatic antioxidant capacity, induces oxidative damage and apoptosis via the xiap-p53-bax-bcl2 and the caspase-dependent pathways, but enhances host immunity by regulating nonspecific immune indices and related genes expression to maintain homeostasis in black rockfish. These findings will help fully understand the hypoxia tolerance mechanisms of black rockfish and provide more data for offshore open ocean farming.

Effect of Dietetic Obesity on Testicular Transcriptome in Cynomolgus Monkeys.

Obesity is a metabolic disorder resulting from behavioral, environmental and heritable causes, and can have a negative impact on male reproduction. There have been few experiments in mice, rats, and rabbits on the effects of obesity on reproduction, which has inhibited the development of better treatments for male subfertility caused by obesity. Nonhuman primates are most similar to human beings in anatomy, physiology, metabolism, and biochemistry and are appropriate subjects for obesity studies. In this investigation, we conducted a transcriptome analysis of the testes of cynomolgus monkeys on high-fat, high-fructose, and cholesterol-rich diets to determine the effect of obesity on gene expression in testes. The results showed that the testes of obese monkeys had abnormal morphology, and their testes transcriptome was significantly different from that of non-obese animals. We identified 507 differentially abundant genes (adjusted p value < 0.01, log2 [FC] > 2) including 163 up-regulated and 344 down-regulated genes. Among the differentially abundant genes were ten regulatory genes, including IRF1, IRF6, HERC5, HERC6, IFIH1, IFIT2, IFIT5, IFI35, RSAD2, and UBQLNL. Gene ontology (GO) and KEGG pathway analysis was conducted, and we found that processes and pathways associated with the blood testes barrier (BTB), immunity, inflammation, and DNA methylation in gametes were preferentially enriched. We also found abnormal expression of genes related to infertility (TDRD5, CLCN2, MORC1, RFX8, SOHLH1, IL2RB, MCIDAS, ZPBP, NFIA, PTPN11, TSC22D3, MAPK6, PLCB1, DCUN1D1, LPIN1, and GATM) and down-regulation of testosterone in monkeys with dietetic obesity. This work not only provides an important reference for research and treatment on male infertility caused by obesity, but also valuable insights into the effects of diet on gene expression in testes.

Wiltse transforaminal thoracic interbody fusion approach for the treatment of single­segment thoracic spinal tuberculosis in elderly patients with osteoporosis: A retrospective study of 20 cases.

The aim of the present study was to investigate the clinical feasibility and efficacy of the Wiltse approach and TTIF in elderly patients with single-segment thoracic tuberculosis (SSTTB) complicated with osteoporosis and neurological dysfunction. Between January 2017 and January 2019, 20 elderly patients underwent the Wiltse TTIF approach at a single hospital. The follow-up time of these patients was 37.15±7.37 months (range, 24-48 months). The preoperative kyphosis angle was 35.41±6.71˚. The degree of neurological deficit in each patient was assessed using the Frankel spinal cord injury classification. In addition, TB activity was monitored using erythrocyte sedimentation rate and C-reactive protein levels, and the degree of osteoporosis was evaluated using femoral neck bone mineral density T-scores. The 20 patients with SSTTB were completely cured without recurrence. The postoperative kyphotic angle was 8.80±0.79˚, without significant loss of correction at the final follow-up. Bone graft fusion was observed within 6-9 months, with all patients reporting relief of their back pain. The neurological condition of all the patients improved postoperatively. The present study indicates that Wiltse TTIF surgery combined with anti-TB chemotherapy has satisfactory efficacy in elderly patients with SSTTB complicated by osteoporosis and neurological impairment.

A Nature-Inspired Separator with Water-Confined and Kinetics-Boosted Effects for Sustainable and High-Utilization Zn Metal Batteries.

Uncontrollable dendrite growth and sluggish ion-transport kinetics are considered as the main obstacles for the further development of high-performance aqueous zinc ion batteries (AZIBs). Here, a nature-inspired separator (ZnHAP/BC) is developed to tackle these issues via the hybridization of the biomass-derived bacterial cellulose (BC) network and nano-hydroxyapatite particles (HAP). The as-prepared ZnHAP/BC separator not only regulates the desolvation process of the hydrated Zn2+ ions (Zn(H2 O)6 2+ ) by suppressing the water reactivity through the surface functional groups, alleviating the water-induced side-reactions, but also boosts the ion-transport kinetics and homogenize the Zn2+ flux, resulting in a fast and uniform Zn deposition. Remarkably, the Zn|Zn symmetric cell with ZnHAP/BC separator harvests a long-term stability over 1600 h at 1 mA cm-2 , 1 mAh cm-2 and endures stable cycling over 1025 and 611 h even at a high depth of discharge (DOD) of 50% and 80%, respectively. The Zn|V2 O5 full cell with a low negative/positive (N/P) capacity ratio of 2.7 achieves a superior capacity retention of 82% after 2500 cycles at 10 A g-1 . Furthermore, the Zn/HAP separator can be totally degraded within 2 weeks. This work develops a novel nature-derived separator and provides insights in constructing functional separators toward sustainable and advanced AZIBs.

Experimental and Numerical Calculation Study on the Slope Stability of the Yellow River Floodplain from Wantan Town to Liuyuankou.

More than two million people live on the floodplains along the middle and lower streams of the Yellow River. The rapid development of industry and agriculture on both sides of the Yellow River has caused serious pollution of the floodplain soil. Erosion by water has led to the destruction of the floodplain which has not only compressed people's living space but also resulted in a large amount of sediment containing heavy metals entering the river, aggravating water pollution. To further study the law governing the release of pollutants in soil, this work, based on field surveys of the Yellow River floodplain slopes from Wantan town to Liuyuankou, was focused on determining the failure mechanism and laws for the floodplain slope through the combination of a flume experiment and numerical calculations. The results showed that the floodplain slopes, composed of clay and silty sand, presented an interactive structure. Under the action of water erosion, the slope was first scoured to form a curved, suspended layer structure, and then the upper suspended layer toppled. The bank stability coefficient decreased by about 65% when the scour width increased from 0.07 m to 0.42 m, and the water content increased from 20% to 40%. For the failure characteristics, the angle of the failure surface was negatively correlated with the scour width, and the distance from the top failure surface to the bank edge was about 2.5 times that of the scour width.

Regulating Zn Ion Desolvation and Deposition Chemistry Toward Durable and Fast Rechargeable Zn Metal Batteries.

The high Zn ion desolvation energy, sluggish Zn deposition kinetics, and top Zn plating pattern are the key challenges toward practical Zn anodes. Herein, these key issues are addressed by introducing zinc pyrovanadate (ZVO) as a solid zinc-ion conductor interface to induce smooth and fast Zn deposition underneath the layer. Electrochemical studies, computational analysis, and in situ observations reveal the boosted desolvation and deposition kinetics, and uniformity by ZVO interface. In addition, the anti-corrosion ability of Zn anodes is improved, resulting in high Zn stripping/plating reversibility. Consequently, the ZVO layer renders fast rechargeability and durable life in both Zn symmetric cells (1050 h at 10 mA cm-2 , 1 mAh cm-2 ) and Zn/V2 O5 batteries (79.1% capacity retention after 1000 cycles at 2 A g-1 ) with low electrode polarization. This work provides insights into the design of solid zinc-ion conductor interface to enhance the interface stability and kinetics of Zn metal anodes.

Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations.

B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.

Tannic acid assisted metal-chelate interphase toward highly stable Zn metal anodes in rechargeable aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) have attracted extensive attention because of their eco-friendliness, intrinsic safety, and high theoretical capacity. Nevertheless, the long-standing Zn anode issues such as dendrite growth, hydrogen evolution, and passivation greatly restrict the further development of AZIBs. Herein, a metal-chelate interphase with high Zn affinity is constructed on the Zn metal surface (TA@Zn) via dipping metallic Zn into a tannic acid (TA) solution to address the aforementioned problems. Benefiting from the abundant hydrophilic and zincophilic phenolic hydroxyl groups of TA molecules, the metal-chelate interphase shows strong attraction for Zn2+ ions, guiding uniform zinc deposition as well as decreasing Zn2+ migration barrier. Therefore, the TA@Zn anode displays an extended lifespan of 850 h at 1 mA cm-2, 1 mAh cm-2 in the Zn|Zn symmetrical cell, and a high Coulombic efficiency of 96.8% in the Zn|Ti asymmetric cell. Furthermore, the Zn|V2O5 full cell using TA@Zn anode delivers an extremely high capacity retention of 95.9% after 750 cycles at 2 A g-1. This simple and effective strategy broadens the interfacial modification scope on Zn metal anodes for advanced rechargeable Zn metal batteries.

Discovery of Novel Tetrahydro-ß-carboline Containing Aminopeptidase N Inhibitors as Cancer Chemosensitizers.

Aminopeptidase N (APN, CD13) is closely associated with the development and progression of cancer. Previous studies suggested APN as a biomarker for cancer stem cells. APN inhibitors have been intensively evaluated as chemosensitizers for cancer treatments. In the present study, tetrahydro-ß-carboline scaffold was introduced to the structure of APN inhibitors. The synthesized compounds showed potent enzyme inhibitory activities compared with Bestatin, an approved APN inhibitor, in cell-based enzymatic assay. In combination with chemotherapeutic drugs, representative APN inhibitor molecules D12, D14 and D16 significantly improved the antiproliferative potency of anticancer drugs in the in vitro tests. Further mechanistic studies revealed that the anticancer effects of these drug combinations are correlated with decreased APN expression, increased ROS level, and induction of cell apoptosis. The spheroid-formation assay and colony-formation assay results showed effectiveness of Paclitaxel-APN inhibitor combination against breast cancer stem cell growth. The combined drug treatment led to reduced mRNA expression of OCT-4, SOX-2 and Nanog in the cancer stem cells tested, suggesting the reduced stemness of the cells. In the in vivo study, the selected APN inhibitors, especially D12, exhibited improved anticancer activity in combination with Paclitaxel compared with Bestatin. Collectively, potent APN inhibitors were discovered, which could be used as lead compounds for tumor chemo-sensitization and cancer stem cell-based therapies.

Identification of TCR repertoires in asymptomatic COVID-19 patients by single-cell T-cell receptor sequencing.

The T cell-mediated immune responses associated with asymptomatic infection (AS) of SARS-CoV-2 remain largely unknown. The diversity of T-cell receptor (TCR) repertoire is essential for generating effective immunity against viral infections in T cell response. Here, we performed the single-cell TCR sequencing of the PBMC samples from five AS subjects, 33 symptomatic COVID-19 patients and eleven healthy controls to investigate the size and the diversity of TCR repertoire. We subsequently analyzed the TCR repertoire diversity, the V and J gene segment deference, and the dominant combination of αß VJ gene pairing among these three study groups. Notably, we revealed significant TCR preference in the AS group, including the skewed usage of TRAV1-2-J33-TRBV6-4-J2-2 and TRAV1-2-J33-TRBV6-1-J2-3. Our findings may shed new light on understanding the immunopathogenesis of COVID-19 and help identify optimal TCRs for development of novel therapeutic strategies against SARS-CoV-2 infection.