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Abstract Objective Immune checkpoint inhibitor (ICI) therapy activates the immune system to recognize and eliminate cancer cells that have escaped surveillance. This study aimed to compare the treatment outcome of advanced and recurrent cervical cancer patients treated with first-line platinum and paclitaxel with or without ICI. Methods Data from 69 advanced and recurrent cervical cancer patients treated with first-line ICI plus platinum and paclitaxel (N = 33) or first-line platinum and paclitaxel (N = 36) were reviewed between March 2020 and January 2023 in this retrospective study. Patients chose treatment based on the actual disease condition, patient willingness, and medical advice. Additionally, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were calculated, and adverse events were gained. Results There was no difference in baseline data between patients receiving the two different treatments (all P > 0.05). Complete response rate (18.2% vs. 8.3%; P = 0.294), ORR (48.5% vs. 30.6%; P = 0.127), and DCR (81.8% vs. 72.2%; P = 0.345) tended to ascend in patients treated with ICI plus platinum and paclitaxel compared to those treated with platinum and paclitaxel, although there was no statistical significance. In patients treated with ICI plus platinum and paclitaxel, the median PFS was 10.3 months and the median OS was not reached. Meanwhile, the median PFS and OS were 7.7 and 16.9 months in patients treated with platinum and paclitaxel. PFS (P = 0.036) and OS (P = 0.033) were increased in patients treated with ICI plus platinum and paclitaxel versus those treated with platinum and paclitaxel, which was verified by multivariate Cox regression analyses (both P 0.05). Conclusion First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum and paclitaxel in advanced and recurrent cervical cancer patients.

Background This randomised controlled study was aimed at investigating the effects of WeChat-based cognitive behavioural stress management (WB-CBSM) on the mental health of patients with early-stage cervical cancer treated with surgical resection.Methods A total of 184 patients with early-stage cervical cancer were randomised to receive either WB-CBSM (n = 92) or normal care (NC) (n = 92) for 8 weeks.Results Compared with the NC group, the WB-CBSM group exhibited reduced Hospital Anxiety and Depression Scale (HADS)–anxiety scores at months (M)1 (t = 2.022, P = 0.045), M3 (t = 2.575, P = 0.011), and M6 (t = 2.709, P = 0.007); anxiety rates at M3 (χ2 = 4.834, P = 0.028) and M6 (χ2 = 5.182, P = 0.023); HADS–depression scores at M3 (t = 2.069, P = 0.040) and M6 (t = 2.449, P = 0.015); and depression rates at M6 (χ2 = 4.268, P = 0.039). Moreover, the WB-CBSM group showed increased Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being scale scores at M1 (t = −2.001, P = 0.047), M3 (t = −2.281, P = 0.024), and M6 (t = −3.501, P = 0.001); the Quality of Life Questionnaire-Core 30 (QLQ-C30) global health score at M3 (t = −2.034, P = 0.043) and M6 (t = −2.426, P = 0.016); and QLQ-C30 function score at M3 (t = −2.009, P = 0.046). However, the groups exhibited decreased EuroQol-5 dimension scores at M3 (t = 2.056, P = 0.041) and M6 ((t = 2.242, P = 0.026) and QLQ-C30 symptom scores at M1 (t = 2.026, P = 0.044) and M3 (t = 2.210, P = 0.028).Conclusion WB-CBSM reduced anxiety and depression and improved the spiritual well-being and quality of life of patients with early-stage cervical cancer treated with surgical resection.

Abstract Tumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.

Abstract Background Laparoscopic treatment shows non-inferior survival outcomes and better surgical outcomes in apparent stage I ovarian cancer (OC) in some studies but has not been well defined. Methods We conducted a retrospective study of patients with apparent stage I OC treated in two hospitals between 2012 and 2022. The surgical and oncologic outcomes were evaluated between patients receiving laparoscopic and laparotomic surgery. Results We identified 37 patients with apparent stage I OC, including 15 (40.5%) serous carcinomas, 9 (24.3%) mucinous cancers, 3 (8.1%) endometroid cancers, 2 clear cell carcinomas, and 8 (21.6%) non-epithelial cancers. Sixteen patients received laparoscopic surgery and the other 21 patients underwent laparotomic surgery. The median age (44.5 vs. 49.0 years), mean mass size (10.5 vs. 11.3 cm), and median follow-up time (43.5 vs. 75.0 months) showed no statistically significant differences between patients in laparoscopic and laparotomic groups (all P > 0.05). All the patients underwent comprehensive surgical staging surgery, and the mean surgical time (213.5 vs. 203.3 min, P = 0.507), number of lymph nodes sampling (18.6 vs. 17.5, P = 0.359), proportion of upstaging (12.5% vs. 19.0%, P = 0.680), and postoperative complications (no Accordion Severity Grading System grade ≥ 3) were comparable between two surgical groups. Moreover, patients in the laparoscopic group had significantly less intraoperative blood loss (231.3 vs. 352.4 mL, P = 0.018), shorter interval between surgery and postoperative adjuvant chemotherapy (7.4 vs. 9.5 days, P = 0.004), shorter length of hospital stay (9.9 vs. 13.8 days, P

In the aftermath of the COVID-19 pandemic, people are gradually realizing that urban community resilience is pivotal for effectively managing public health emergencies. This study employed grounded theory to establish a theoretical framework for epidemic resilience of urban communities (ERUC) in the post-pandemic era. Subsequently, the decision-making trial and evaluation laboratory (DEMATEL)-interpretive structural modeling (ISM) method is utilized to discern the significance and hierarchical interrelations among influencing factors. The findings delineate that 14 determinants shaping ERUC are organized into five distinct tiers. Notably, nine determinants emerge as principal: vulnerable group; educational attainment; risk perception; medical insurance coverage; communal norms; community emergency response; community services; resident participation; and government efficacy. Among these, the vulnerable group and government efficiency are identified as foundational factors, while medical insurance coverage, resident participation, and community infrastructure are identified as direct influences.

Reanalysis and satellite retrieval are two primary approaches for obtaining large-scale and long-term Aerosol Optical Depth (AOD) datasets. This study evaluates and compares the accuracy, long-term stability, and error characteristics of the MERRA-2, MODIS combined Dark Target and Deep Blue (DT&DB), and VIIRS DB AOD products globally and regionally. The results indicate that the MERRA-2 AOD exhibits the highest accuracy with an expected error (EE, ±0.05 ± 20%) of 83.24% and mean absolute error (MAE) of 0.056, maintaining a stability of 0.010 per decade. However, since the MERRA-2 AOD ceased assimilating observations other than the MODIS AOD in 2014, its accuracy decreased by approximately 5.6% in the EE metric after 2014. The VIIRS Deep Blue (DB) AOD product, with an EE of 79.43% and stability of 0.016 per decade, is slightly less accurate and stable compared to the MERRA-2 AOD. The MODIS DT&DB AOD demonstrates an EE of 76.75% and stability of 0.011 per decade. Regionally, the MERRA-2 AOD performs acceptably in most areas, especially in low-aerosol-loading regions, with an EE > 86% and stability ~0.02 per decade. The VIIRS DB AOD excels in high-aerosol-loading regions, such as the Indian subcontinent, with an EE of 69.14% and a stability of 0.049 per decade. The performance of the MODIS DT&DB AOD falls between that of VIIRS DB and MERRA-2 across most regions. Overall, each product meets the accuracy and stability metrics globally, but users need to select the appropriate product for analysis based on the validation results of the accuracy and stability in different regions.

Objectives This study explored the association between the Frailty Index (FI) and low back pain (LBP) in middle-aged and older Chinese adults. We hypothesised that a higher FI correlates with increased LBP prevalence.Design Cross-sectional analysis.Setting The study used data from the China Health and Retirement Longitudinal Study (CHARLS) across various regions of China.Participants The analysis included 6375 participants aged 45 and above with complete LBP and FI data from the CHARLS for 2011, 2013 and 2015. We excluded individuals under 45, those with incomplete LBP data, participants with fewer than 30 health deficit items and those missing covariate data.Outcome measures We constructed an FI consisting of 35 health deficits. Logistic multivariable regression examined the relationship between FI and LBP, using threshold analysis to identify inflection points. Sensitivity analyses were performed to ensure the robustness of the findings.Results Of the participants, 27.2% reported LBP. A U-shaped association was observed between FI and LBP, with the highest quartile (Q4, FI ≥0.23) showing more than a twofold increased risk of LBP (OR=2.90, 95% CI: 2.45–3.42, p

Salvia miltiorrhiza Bunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1 % in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.

Summary: Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Abstract Background Immense attention has been given to the outcome of COVID-19 infection. However, comprehensive studies based on large populational cohort with long-term follow-up are still lacking. This study aimed to investigate the risk of various short-term comorbidities (within one month) and long-term sequelae (above one month) after COVID-19 infection. Methods In this large prospective cohort study with 14 months follow-up information based on UK biobank, we included 16,776 COVID-19-positive participants and 58,281 COVID-19-negative participants matched for comparison. The risk of each comorbidity and sequela was evaluated by multivariable logistic regression analysis and presented as hazard ratio (HR) and 95% confidence interval (95% CI). Results COVID-19-positive individuals had a higher risk of 47 types of comorbidities within one month following COVID-19 infection, especially those who were older, male, overweight/obese, ever-smoked, with more pre-existing comorbidities and hospitalized. About 70.37% of COVID-19 patients with comorbidities had more than one co-occurring comorbidities. Additionally, only 6 high-risk sequelae were observed after one month of COVID-19 infection, and the incidence was relatively low (

Abstract Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.

Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines.

Abstract Objective To evaluate the effect of overall peripheral inflammatory levels on cognitive function, we explored the relationship between established biomarkers of peripheral inflammation (circulating C‐reactive protein [CRP], interleukin‐6 [IL‐6], and tumor necrosis factor‐α [TNF‐α]) and cognitive decline by performing a review of observational studies and creating an updated summary. Methods We included literatures exploring the relationship between peripheral levels of CRP, IL‐6, and TNF‐α and subsequent cognitive decline, published until July 2022, by searching the following databases: PubMed, Embase, Web of Science, the Cochrane Library, ClinicalTrials, CNKI, and VIP databases. We used random‐effects models to pool the odds ratios (ORs) for the risks of subsequent cognitive decline in older adults with high levels of peripheral inflammation. We initially screened out 501 literatures, of which only 17 were ultimately eligible. Overall, there were 19,516 older individuals included in our meta‐analysis, and 2134 of them experienced subsequent cognitive change. Results Individuals with high levels of peripheral inflammation may have 14% more chance to develop subsequent cognitive decline than those with low levels (OR = 1.14, 95% CI: 1.03–1.27; p

Abstract Background Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway. Methods Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined. Results We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro. Conclusion Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.

Due to the lower operating voltage and higher theoretical specific capacity, tin phosphide is considered a class of materials with prospects as an anode material for lithium-ion batteries (LIBs). Among them, tin monophosphide has attracted people's attention due to its unique layered structure. Unfortunately, because of the challenging synthesis method and metastable nature, the application of SnP is limited. In this work, tin phosphide/carbon nanotubes (SnP/CNTs) are prepared by controlling the nucleation and adjusting the ratio of phosphorus/carbon using carbon nanotube as initiator. Sn-MOF is used as a template to make the morphology of SnP more evenly, and carbon nanotubes can also be used as a conductive network to increase the speed of electron transmission. As an anode material for LIBs, SnP/CNTs reveals superior rate performances (reversible capability of 610 mA·h·g−1 at 2 000 mA·g−1). The full-cell was assembled and tested, after 50 cycles at 0.1 C, the capacity can maintain 292 mA·h·g−1, and its capacity retention rate can reach 80.5%. After 230 cycles, its capacity can maintain at around 223 mA·h·g−1. In addition, SnP/CNTs materials exhibit 89% pseudocapacitance contribution upon cycling, which indicates the robust Li+ storage and satisfactory fast-charging capability. Hence, SnP/CNTs suggests a promising anode material for energy storage system.

Bacterial ghosts (BGs) are hollow bacterial cell envelopes with intact cellular structures, presenting as promising candidates for various biotechnological and biomedical applications. However, the yield and productivity of BGs have encountered limitations, hindering their large-scale preparation and multi-faceted applications of BGs. Further optimization of BGs is needed for the commercial application of BG technology. In this study, we screened out the most effective lysis protein ID52-E-W4A among 13 mutants based on phage ID52 lysis protein E and optimized the liquid culture medium for preparing Escherichia coli Nissle 1917 (EcN). The results revealed a significantly higher lysis rate of ID52-E-W4A compared to that of ID52-E in the 2xYT medium. Furthermore, EcN BGs were cultivated in a fermenter, achieving an initial OD600 as high as 6.0 after optimization, indicating enhanced BG production. Moreover, the yield of ID52-E-W4A-induced BGs reached 67.0%, contrasting with only a 3.1% yield from φX174-E-induced BGs. The extended applicability of the lysis protein ID52-E-W4A was demonstrated through the preparation of Salmonella pullorum ghosts and Salmonella choleraesuis ghosts. Knocking out the molecular chaperone gene slyD and dnaJ revealed that ID52-mediated BGs could still undergo lysis. Conversely, overexpression of integral membrane enzyme gene mraY resulted in the loss of lysis activity for ID52-E, suggesting that the lysis protein ID52-E may no longer rely on SlyD or DnaJ to function, with MraY potentially being the target of ID52-E. This study introduces a novel approach utilizing ID52-E-W4A for recombinant expression, accelerating the BG formation and thereby enhancing BG yield and productivity.

Objectives To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases.Design Retrospective cohort study.Setting UK Biobank.Participants A total of 500 371 subjects aged 40–69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex.Exposure Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank.Primary and secondary outcome measures The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively.Results During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p

Gastric ulcer (GU) is one of the most prevalent digestive diseases that seriously affects people’s health. Previous studies have demonstrated the anti-GU effect of Ruda-6 (RD-6), a classic formulae of traditional Mongolian medicine. However, the underlying mechanism of RD-6 against GU remains elusive. Thus, we conducted an integrative approach of network analysis, RNA-seq, and in vivo validation experiment to elucidate the therapeutic mechanisms of RD-6 in preventing GU. A network analysis was performed to predict the potential targets of RD-6. Rats were pretreated with RD-6 at different doses for 21 days, followed by GU induction with indomethacin injection. The ulcer index and inhibition rates were calculated, and the levels of inflammatory related factors were determined by ELISA. The gastroprotective mechanism of RD-6 against ulceration was verified by RNA-seq and the key pathway was detected by in vivo validation. As the network analysis predicted, RD-6 exerts anti-GU effects by regulating 75 targets and 160 signaling pathways. Animal experiment results suggested that pretreatment with RD-6 significantly ameliorated the gastric mucosal injury and inflammatory response, as evidenced by a reduced ulcer index, decreased interleukin (IL)-1β, IL-6, and IL-17 levels, and increased prostaglandin E2 (PGE2) levels in the GU model rats induced by indomethacin. RNA-seq data identified four potential hub genes that were primarily involved in the IL-17 signaling pathway. Furthermore, in vivo validation experiment showed that RD-6 inhibited the IL-17 signaling pathway by down-regulating the expression of IL17RA, proto-oncogene C-Fos (FOS), IL1B and prostaglandin-endoperoxide synthase 2 (PTGS2). Taken together, the present study provides evidence that RD-6 could effectively protect against indomethacin-induced GU, which might be attributed to suppressed inflammation. The IL-17 signaling pathway may be one of the crucial mechanisms that mediates the effect of RD-6.

Abstract Background and objective High-frequency ultrasound plays an extremely important role in normal skin measurement, skin disease diagnosis, and aesthetic medicine. This study aimed to estimate the epidermal and dermal thicknesses at eight different facial sites in healthy adults using high-frequency ultrasound, and to evaluate the correlation of epidermal and dermal thicknesses with age and body mass index (BMI). Methods Facial skin assessment was performed on 118 participants using high-frequency ultrasound. The epidermal and dermal thicknesses of forehead, glabella, temple, eyelid, nasal dorsum, zygoma, submandibular, and neck were measured. The correlation of the epidermal and dermal thicknesses with age and BMI was analyzed by the linear correlation analysis. Results The epidermal and dermal thicknesses in men were significantly higher than those in women (P

Compared to chemical drugs, therapeutic proteins exhibit higher specificity and activity and are generally well-tolerated by the human body. However, the limitations, such as poor stability both in vivo and in vitro as well as difficulties in penetrating cell membranes, hinder their widespread application. To overcome the challenges, a highly efficient protocol was developed and implemented for the recombinant expression of the therapeutic protein azurin and secretion into minicells derived from probiotic Escherichia coli Nissle 1917. The novel coupled production with a delivery system of therapeutic proteins based on minicells was obtained through purification to enhance protein activity, circulation characteristics, and targeting specificity. This protein drug carrier integrates the production of carrier materials and the loading of expression proteins. The drug carrier also protects the encapsulated polypeptide drugs from enzymatic or gastric acid degradation until they are released. Escherichia coli Nissle 1917-derived minicells have natural targeting to colon cancer cells, low toxicity, and can accumulate for a long time after penetrating tumor tissue. This self-produced protein drug delivery system simplified the process of protein preparation, and its inhibitory effect on different types of colon cancer cells was verified by CCK-8 cytotoxicity assay, cancer cell invasion, and migration assay. This work provided a simple method to prepare minicell drug delivery systems for protein drug production and a novel approach for the transport of recombinant protein drugs.

Yellowhorn tea (YT) is traditionally used as a lipid-lowering beverage in Mongolian minorities. However, the pharmacological effects of YT extract and its specific metabolic changes in hyperlipidemia models are not fully understood. The aim of this study was to identify biomarkers using untargeted metabolomics techniques and to investigate the mechanisms underlying the changes in metabolic pathways associated with lipid lowering, anti-inflammation and anti-oxidant in hyperlipidemic mice. A high-fat diet (HFD)-induced hyperlipidemic mouse model was established. YT extract was administered as oral gavage at 0.15, 0.3, and 0.6 g/kg doses for 10 weeks. HFD-induced hyperlipidemia and the therapeutic effect of YT extract were evaluated based on histopathology and by assessing blood lipid levels. Liver inflammatory factors and oxidative stress indices were determined using enzyme-linked immunosorbent assays. Liver metabolites were evaluated using untargeted metabolomics. Biochemical and histological examinations showed that YT extract significantly reduced body-weight gain (p < 0.01) and fat deposition in tissues. YT extract significantly reduced the levels of serum and liver triglyceride and total cholesterol; inflammatory factors [interleukin (IL)-6, IL-1β, and tumor necrosis factor-α]; malondialdehyde; and leptin (p < 0.05) in hyperlipidemic mice. YT extract also significantly increased the levels of oxidative stress indicators (superoxide dismutase, catalase, and glutathione peroxidase) and adiponectin. Metabolomics studies revealed several endogenous molecules were altered by the high-fat diet and recovery following intervention with YT extract. The metabolites that were significantly different in the liver after YT intake included citicoline, acetylcholine, pyridoxine, and NAD. Pathway analysis indicated that YT extract ameliorated HFD-induced hyperlipidemia in mice via three major metabolic pathways, namely, glycerophospholipid metabolism, vitamin B6 metabolism, and nicotinate and nicotinamide metabolism. This study demonstrates YT extract has profound effects on the alleviation of HFD-induced hyperlipidemia, inflammation and oxidative stress.

In the past ten years, terahertz technology has developed rapidly in wireless communications, spectroscopy, and imaging. Various functional devices have been developed, such as filters, absorbers, polarizers, mixers, and modulators. Among these, the terahertz phase modulation is a current research hotspot. It is the core technology to realize flexible control of the terahertz wavefront, beam scanning, focusing deflection. It is indispensable in terahertz wireless communication, high-resolution imaging, and radar systems. This review summarizes the research progress of terahertz phase modulators from the two major types: free space and guided wave integration. Among these, the free space terahertz phase modulator is realized by combining the tunable materials and artificial metasurfaces. Based on different types of tunable materials, the terahertz free space phase modulator combining the semiconductor, liquid crystal, phase change materials, graphene, and other two-dimensional materials are introduced, and the influence of different materials on the phase modulation performance is discussed and analyzed. The monolithic integration and waveguide embedding methods are introduced separately, and the characteristics of different forms of terahertz-guided wave phase modulation are also discussed. Finally, the development trends of terahertz phase modulators, possible new methods, and future application requirements are discussed.

The activation of Yes-associated protein (YAP) pathway is mutually causal with the increase of extracellular matrix (ECM) stiffness. Polydatin (PD) has been proved to have anti-fibrosis effect in diabetic kidney disease (DKD), but it is still a mystery whether PD participates in YAP-related mechano-transduction. Therefore, this study intends to solve the following two problems: 1) To construct an in vitro system of polyacrylamide hydrogels (PA gels) based on the true stiffness of kidneys in healthy and DKD rats, and observe the effect of PD on pathological matrix stiffness-induced YAP expression in renal fibroblasts; 2) Compared with verteporfin (VP), a pharmacological inhibitor of YAP, to explore whether the therapeutic effect of PD on DKD in vivo model is related to the regulation of YAP. In this study, the in vitro system of PA gels with 3 kPa, 12 kPa and 30 kPa stiffness was constructed and determined for the first time to simulate the kidney stiffness of healthy rats, rats with DKD for 8 weeks and 16 weeks, respectively. Compared with the PA gels with 3 kPa stiffness, the PA gels with 12 kPa and 30 kPa stiffness significantly increased the expression of YAP, α-smooth muscle actin (α-SMA) and collagen I, and the production of reactive oxygen species (ROS) in renal fibroblasts, and the PA gels with 30 kPa stiffness were the highest. PD significantly inhibited the above-mentioned changes of fibroblasts induced by pathological matrix stiffness, suggesting that the inhibition of PD on fibroblast-to-myofibroblast transformation and ECM production was at least partially associated with regulating YAP-related mechano-transduction pathway. Importantly, the inhibitory effect of PD on YAP expression and nuclear translocation in kidneys of DKD rats is similar to that of VP, but PD is superior to VP in reducing urinary protein, blood glucose, blood urea nitrogen and serum creatinine, as well as decreasing the expression of α-SMA and collagen I, ROS overproduction and renal fibrosis. Our results prove for the first time from the biomechanical point of view that PD is a potential therapeutic strategy for delaying the progression of renal fibrosis by inhibiting YAP expression and nuclear translocation.

Background: Cellular senescence plays a complicated and vital role in cancer development because of its divergent effects on tumorigenicity. However, the long non-coding RNAs (lncRNAs) associated with tumor senescence and their prognostic value in hepatocellular carcinoma (HCC) remain unexplored.Methods: The trans-cancer oncogene-induced senescence (OIS) signature was determined by gene set variation analysis (GSVA) in the cancer genome atlas (TCGA) dataset. The OIS-related lncRNAs were identified by correlation analyses. Cox regression analyses were used to screen lncRNAs associated with prognosis, and an optimal predictive model was created by regression analysis of the least absolute shrinkage and selection operator (LASSO). The performance of the model was evaluated by Kaplan-Meier survival analyses, nomograms, stratified survival analyses, and receiver operating characteristic curve (ROC) analyses. Gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) were carried out to explore the functional relevance and immune cell infiltration, respectively.Results: Firstly, we examined the pan-cancer OIS signature, and found several types of cancer with OIS strongly associated with the survival of patients, including HCC. Subsequently, based on the OIS signature, we identified 76 OIS-related lncRNAs with prognostic values in HCC. We then established an optimal prognostic model based on 11 (including NRAV, AC015908.3, MIR100HG, AL365203.2, AC009005.1, SNHG3, LINC01138, AC090192.2, AC008622.2, AL139423.1, and AC026356.1) of these lncRNAs by LASSO-Cox regression analysis. It was then confirmed that the risk score was an independent and potential risk indicator for overall survival (OS) (HR [95% CI] = 4.90 [2.74–8.70], p < 0.001), which outperforms those traditional clinicopathological factors. Furthermore, patients with higher risk scores also showed more advanced levels of a proinflammatory senescence-associated secretory phenotype (SASP), higher infiltration of regulatory T (Treg) cells and lower infiltration of naïve B cells, suggesting the regulatory effects of OIS on immune microenvironment. Additionally, we identified NRAV as a representative OIS-related lncRNA, which is over-expressed in HCC tumors mainly driven by DNA hypomethylation.Conclusion: Based on 11 OIS-related lncRNAs, we established a promising prognostic predictor for HCC patients, and highlighted the potential immune microenvironment-modulatory roles of OIS in HCC, providing a broad molecular perspective of tumor senescence.

Cities are the main emission sources of the CO2 produced by energy use around the globe and have a great impact on the variation of climate. Although the implications of urbanization and socioeconomic elements for carbon emission have been extensively explored, previous studies have mostly focused on developed cities, and there is a lack of research into naturally related elements due to the limited data. At present, remote sensing data provide favorable conditions for the study of large-scale and long-time series. Also, the spillover mechanism of urbanization effects on the discharge of carbon has not been fully studied. Therefore, it is necessary to distinguish the types of influence that various urbanization factors have on emissions of CO2. Firstly, this study quantifies the urban CO2 emissions in China by utilizing nighttime lighting images. Then, the spatio-temporal variations and spatial dependence modes of CO2 emissions are explored for 284 cities in China from 2000–2018. Finally, the study further ascertains that multi-dimensional urbanization, socio-economic and climate variables affect the discharge of carbon using spatial regression models. The results indicate that CO2 emissions have a remarkable positive spatial autocorrelation. Urbanization significantly increases CO2 emissions, of which the land urbanization contribution towards CO2 emissions is the most important in terms of spillover effects. Specifically, the data on urbanization’s direct effects reveal that CO2 emissions will increase 0.066%when the urbanization level of a city rises 1%, while the spillover effect indicates that an 0.492% emissions increase is associated with a 1% rise of bordering cities’ average urbanization level. As for the socio-economic factors, population density suppresses CO2 emissions, while technological levels boost CO2 emissions. The natural control factors effect a remarkable impact on CO2 emissions by adjusting energy consumption. This study can provide evidence for regional joint prevention in urban energy conservation, emission reduction, and climate change mitigation.

Abstract To investigate the feasibility of using ICAM-1-targeted nano ultrasonic contrast to evaluate the degree of inflammatory injury at different stages in the abdominal aorta of rabbits with atherosclerosis (AS). Twenty-five experimental rabbits were assigned to five groups: the control group (A); the week-4 after modeling group (B); the week-8 after modeling group (C); the week-12 after modeling group (D); the week-16 after modeling group (E). All groups were given 2D ultrasonography, conventional ultrasonic contrast (SonoVue), and ICAM-1-targeted nano ultrasonic contrast, respectively. Signal intensity of vascular perfusion was evaluated. Signal intensity of ICAM-1-targeted nano ultrasonic contrast was substantially enhanced and prolonged in the vascular wall of the abdominal bubble aorta increased in B, C, D, and E groups (all P

Background and Objectives: Aucklandiae Radix is a well-known medicinal herb that is often used to treat gastric ulcer, but its molecular mechanism of anti-ulcer action is poorly understood. This research aimed to reveal the potential active components, core targets, and mechanisms of Aucklandiae Radix in treating gastric ulcer by combining network pharmacology and animal experimentation. Materials and Methods: First, a network pharmacology strategy was used to predict the main components, candidate targets, and potential signaling pathways. Molecular docking was then used to confirm the binding affinity between the main components and primary targets. Finally, rats were treated with indomethacin 30 mg/kg to establish a gastric ulcer model. Aucklandiae Radix extract (0.15, 0.3, and 0.6 g/kg) was pre-treated in rats by oral gavage for 14 days, and the protective effect and candidate targets of network pharmacology were validated through morphological observation, pathological staining, and biochemical index detection. Results: A total of eight potential active components and 331 predicted targets were screened from Aucklandiae Radix, 37 of which were common targets with gastric ulcer. According to the component–target network and protein-protein interaction (PPI) network, stigmasterol, mairin, sitosterol, and dehydrocostus lactone were identified as the key components, and RAC-alpha serine/threonine-protein kinase (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 1 beta (IL1B), caspase-3 (CASP3), and CASP8 were selected as the core targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment results revealed the pharmacological mechanism of Aucklandiae Radix against gastric ulcer related to many biological processes and pathways, including antibacterial, anti-inflammatory, prostaglandin receptor response, and apoptosis. Molecular docking verification showed that the key components and core targets had good binding affinities. In the in vivo experiments, Aucklandiae Radix notably relieved the gastric ulcer by reducing the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) while improving the gastric histopathological features. Conclusion: The overall findings suggest that Aucklandiae Radix treats gastric ulcer with a multi-component, multi-target, and multi-mechanism model.

Human γδ T lymphocytes were reported to display anti-tumor effects against multiple cancers, including hepatocellular carcinoma (HCC). Aberrant expression of microRNAs (miRNAs) leads to a low response to immunotherapy. Thirty-five HCC tumor tissues and their adjacent healthy tissues were collected from patients with primary HCC who underwent tumor resection in the Third People’s Hospital of Hainan Province, China. The purity of the resulting γδ T cells was identified by anti-γδ-T cell receptor-phycoerythrin (anti-γδ-TCR-PE) and anti-CD3-fluorescein isothiocyanate (anti-CD3-FITC) antibodies on flow cytometry. Human HCC cell lines HepG2 and PLC were cultured. We observed that ex vivo, expanded human γδ T cells were able to induce cell lysis of HCC. Furthermore, as miR-382 was observed to be downregulated in HCC tissues and cell lines, we found that overexpression of miR-382 increased the sensitivity of HCC cells to γδ T cells. We proved that mRNA of cellular FADD-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP) was the target of miR-382. Inhibition of c-FLIP by miR-382 significantly promotes the cell lysis of HCC through strengthening the activation caspase 8 induced by γδ T cell treatment. In conclusion, overexpression of miR-382 promotes HCC cell lysis induced by γδ T cells through inhibiting the expression of c-FLIP.

The current study investigated the effects of gamma radiation on the death rate, morphological traits and meiotic abnormalities in ground-grown chrysanthemum ‘Donglinruixue’, and inter-simple sequence repeat (ISSR) markers were used to identify the DNA polymorphism among mutants. The results showed that the death rate significantly increased with increase in radiation dose. Semi-lethal (LD50) dose was approximately 35 Gy. Compared with unirradiated control, plant growth was significantly inhibited. After irradiation, a series of morphological variations and cytological aberrations occurred in radiated plants. The peak in variation frequency appeared at 35 Gy. In total, ISSR analysis produced 72 scorable bands, of which 64 (88.89%) were polymorphic. The current study demonstrated that gamma irradiation generates a sufficient number of induced mutations and that ISSR analysis offered a useful molecular marker analysis for the identification of mutants.

With the acceleration of urbanization, the demand for land due to urban large-scale construction and development is increasing. Coastal reclamation (CR) is a prevailing approach to tackle the contradiction between coastal land shortage and the growing demand for living space for human beings. Enormous social and economic benefits are derived from CR, while at the same time bringing a series of environmental problems. Since the beginning of the 21st century, this oceanic-oriented development has become more frequent. Therefore, the considerable economic and ecological trade-offs of reclamation activities must be analyzed to enable targeted land use decisions. By comprehensively evaluating the natural conditions of the sea area, including geology, topography, hydrology, ecology, and social and economic conditions, this study established an environmental capacity assessment system (ECAS) based on water environmental capacity for assessment of the potential environmental impact resulting from CR. According to the water quality status and positions of CR in Haizhou Bay, the environmental capacities of four major pollutants were calculated to forecast the suitable area of CR. The results indicated that these reclamation projects had notable negative effects on the environmental capacity of the four major pollutants. The order of pollutants according to their harm on seawater quality is: PO4-P > NH4-N > NOX-N > COD. In three reclamation alternative scenarios, scenario 3 led to the minimum negative impacts on the environmental capacity, scenario 2 followed, and scenario 1 had the worst result. Hence, scenario 3 was the optimal reclamation scenario, under which the suitable area of CR in Haizhou Bay was found to be 83 km2. This study provides a scientific reference for the effective management of coastal reclamation and future environmental impact research when new CR is proposed, as well as sustainable urban development.

At present,the common food nutrients with hypoglycemic effect were divided into five categories：water-soluble dietary fiber,polysaccharides,flavonoids,saponins,trace elements.Animal experiments are mostly used to study the hypoglycemic effect of related nutrients.The hypoglycemic efficacy and its mechanism of the nutrients with different variety,different sources and different doses on diabetic mice and rats were systematically analyzed and summarized,in order to provide scientific and reasonable suggestions about the daily dietary choice for diabetic patients,and to offer reference for the research and development of health food suitable for diabetic patients.

In this paper, the enhanced terahertz (THz) electromagnetically induced transparency (EIT) resonance is achieved based on the coupled electric field dropping effect within the undulated meta-surface. It is found that the height difference between the inner ring and the outer split ring could lead to a significant coupled mode with electric field dropping distribution. When the height of the inner ring increases, the electric field of the inner ring gradually cascades to the outer ring just as a waterfall so that the coupling between the two rings in a unit cell and two adjacent units is enhanced. Both the simulation and experimental results show that a nearly 95% transparency window which is twice that of traditional EIT can be observed by applying such coupled electric field dropping effect, which may provide a promising way to develop the high resonance intensity meta-surface in the THz region.

Three parallel Visible/Infrared Imager Radiometer Suite (VIIRS) aerosol products (SOAR, NOAA, and AERDT) provided data since 2012. It is necessary to study the performances and advantages of different products. This study aims to analyze the accuracy and error of these products over the ocean and compare them with each other. The results show that the three VIIRS ocean aerosol retrievals (including total aerosol optical depth (AOD), fine mode fraction, Ångström exponent (AE), and fine AOD (AODF)) correlate well with AErosol RObotic NETwork (AERONET) retrievals (e.g., correlation >0.895 for AOD and >0.825 for AE), which are comparable to the newest moderate-resolution imaging spectro-radiometer (MODIS) retrievals. Overall, the SOAR retrievals with quality filtering have the best validation accuracy of all parameters. Therefore, it is more recommended to use. The differences in the annual AOD spatial patterns of different products are small (bias < 0.016), but their AE spatial patterns are evidently different (bias > 0.315), indicating the large uncertainty of VIIRS AE. Error analysis shows that the scattering angle and wind speed affect aerosol retrieval. Application of the non-spherical dust model may reduce the dependence of retrieval bias on the scattering angle. Overall, this study provides validation support for VIIRS products usage and possible algorithm improvements.

Yaks provide necessities such as meat and milk for Tibetans living at high altitudes on and around the Qinghai-Tibetan Plateau. Enterococci are ubiquitous members of the animal gut microbiota that can cause biofilm-associated opportunistic infections. Meanwhile, multidrug-resistant Enterococcus also poses a serious threat to public health. This study aims to characterize antibiotic resistance, virulence genes, and biofilm formation of enterococci from yaks. From April 2018 to July 2019, we collected 395 fecal samples of yaks in Aba Tibetan Autonomous Prefecture, China. Enterococci isolated from the samples were identified and classified according to the 16S rDNA sequence. The antibiotic resistance of each isolate was detected according to the Kirby-Bauer disk diffusion method, and antibiotic resistance genes were detected by polymerase chain reaction (PCR) and sequencing. Enterococcal biofilms were assessed using standard procedures. Different virulence genes were detected by PCR and sequencing. In total, 381 enterococci strains were recovered, with Enterococcus faecalis (41.99%) and Enterococcus faecium (37.80%) being the predominant species. Many isolates were multidrug- resistant (60.37%) and showed a high resistance rate to rifampicin (64.30%) and tetracycline (61.54%). We also detected various antimicrobial resistance (AMR) genes in the tested strains. The E. faecalis strains had higher frequency of biofilm formation and virulence genes than other enterococcal species. This is the first report that shows yaks are repositories for drug-resistant enterococci with virulent determinants and biofilms that may spread into humans and to environment. This study also provides useful data suggesting that enterococci may pose a potential health risk to yaks. Therefore, active surveillance of AMR and pathogenesis in enterococci from yaks is urgently warranted.

Two-dimensional structural transition metal dichalcogenides (2D TMDs) have the advantages of superb thermal and chemical stability, distinctive layered structures, and ultrathin thicknesses, which make them potential candidates in the microwave absorption field. The recent progress in 2D TMDs and their composite nanomaterials with enhanced microwave absorption performance are reviewed here. The synthesis methods, and the microwave absorption properties, including the maximum reflection loss value and effective absorption bandwidth of various 2D TMD nanocomposites, are described in detail. Furthermore, the current challenges and future prospects for the development of 2D TMDs are raised.

Terahertz (THz) science and technology promise unique applications in high-speed communications, high-accuracy imaging, and so on. To keep up with the demand for THz systems, THz dynamic devices should feature large phase shift modulation and high speed. To date, however, only a few devices can efficiently manipulate the phase of THz waves. In this paper, we demonstrate that efficient phase modulation of THz waves can be addressed by an active and enhanced resonant metamaterial embedded with a nanostructured 2D electron gas (2DEG) layer of a GaN high electron mobility transistor (HEMT). The enhanced resonant metaunit couples the traditional dipolar and inductance-capacitance resonances together to realize a coupling mode with enhanced resonance. Embedded with the nanostructured 2DEG layer of GaN HEMT, the resonance intensity and surface current circuit of the enhanced resonant mode in the metamaterial unit can be dynamically manipulated by the electrical control of the carrier distribution and depletion of the 3 nm 2DEG, leading to a phase shift greater than 150° in simulation. In the dynamic experiments, a 137° phase shift was achieved with an external controlling voltage of only several volts in the THz transmission mode. This work represents the first realization of a phase shift greater than 100° in a dynamic experiment in transmission mode using an active metamaterial structure with only a single layer. In addition, given the high-speed modulation ability of the HEMT, this concept provides a promising approach for the development of a fast and effective phase modulator in THz application systems.

Salmonella enterica subsp. enterica serovar Derby (S. Derby) is one of the numerous non-typhoidal Salmonella serovars and has been recognized as a food-borne pathogen. In 2019, outbreaks of salmonellosis were reported in 13 yak farms in the Aba Tibetan Autonomous Prefecture, China. A total of 32 salmonella strains were isolated from 162 fecal samples of yaks with diarrhea as well as from drinking water samples. The isolates were subjected to serovar identification, animal experiments, and whole-genome sequencing (WGS) analyses. The serovar of all the isolates was S. Derby, and the sequence types (STs) were ST40. The analysis of the differences of single-nucleotide polymorphisms (SNPs) showed that the salmonella strains isolated from 13 farms were clonally related. Animal experiments showed that the lethal dose (LD50) was 4.57 × 107 CFU (colony-forming units); the shedding time of S. Derby in mice was 24 days; the bacterial loads in spleen were higher than those in other organs (ileum, liver, and cecum). Pathological analyses by hematoxylin and eosin (H&E) staining revealed obvious damage in the spleen, liver, and intestine. These results indicate that the S. Derby from yaks can cause infection in mice.

Potassium-ion batteries (KIBs) have come up as a potential alternative to lithium-ion batteries due to abundant potassium storage in the crust. Red phosphorus is a promising anode material for KIBs with abundant resources and high theoretical capacity. Nevertheless, large volume expansion, low electronic conductivity, and limited K+ charging speed in red phosphorus upon cycling have severely hindered the development of red phosphorus-based anodes. To obtain improved conductivity and structural stability, surface engineering of red phosphorus is required. Poly(3,4-ethylenedioxythiophene) (PEDOT)-coated red phosphorus nanospheres (RPNP@PEDOT) with an average diameter of 60 nm were synthesized via a facile solution-phase approach. PEDOT can relieve the volume change of red phosphorus and promote electron/ion transportation during charge−discharge cycles, which is partially corroborated by our DFT calculations. A specific capacity of 402 mAh g−1 at 0.1 A g−1 after 40 cycles, and a specific capacity of 302 mAh g−1 at 0.5 A g−1 after 275 cycles, were achieved by RPNP@PEDOT anode with a high pseudocapacitive contribution of 62%. The surface–interface engineering for the organic–inorganic composite of RPNP@PEDOT provides a novel perspective for broad applications of red phosphorus-based KIBs in fast charging occasions.

Abstract Cathelicidins are regarded as promising antibiotics due to their capability against antibiotic-resistant bacteria without cytotoxicity. However, some concerns about the balance of cytotoxicity and antimicrobial activity, weak stability and enzymatic susceptibility sually restrict their therapeutic use. Here, we designed a series of shortened variants, Hc1~15, based on our previously characterized Hc-CATH. Hc3, the one with the best activity, after point mutation was engineered with a trypsin inhibitor loop, ORB-C, to obtain four hybrid peptides: H3TI, TIH3, H3TIF and TIH3F. All four except TIH3 were found possessing an appreciable profile of proteases inhibitory and antimicrobial characteristics without increase in cytotoxicity. Among them, TIH3F exhibited the most potent and broad-spectrum antimicrobial and anti-inflammatory activities. Fluorescence spectroscopy has demonstrated a quick induction of bacterial membrane permeability by TIH3F leading to the cell death, which also accounts for its fast anti-biofilm activity. Such mode of antimicrobial action was mainly attributed to peptides’ amphiphilic and helical structures determined by CD and homology modeling. Besides, TIH3F exhibited good tolerance to salt, serum, pH, and temperature, indicating a much better physiological stability in vitro than Hc3, Most importantly, in the case of resistance against proteases hydrolysis, current hybrid peptides displayed a remarkable enhancement than their original templates.

Objective A 29-year-old male from Guizhou, China, had been suffering from obsessive–compulsive disorder since graduation from junior high school at 14 years. He was afraid of putting glass substances in his mouth. His main symptoms were repetitive thoughts, inquiries and examinations for more than 6 hours a day. He dropped out of school and stayed at home. He had been taking 60 mg/day paroxetine for 7 consecutive years. Over the past 2 years, his obsessive–compulsive symptoms had increased and were present for 12 hours a day. Methods The patient was treated using a combination of drugs, transcutaneous electrical acupoint stimulation–exposure and response prevention therapy (TEAS–ERP) and parental involvement. Results After 28 days, his Yale–Brown Obsessive Compulsive Scale score dropped from 40 to 11 points. After 1 month, telephone follow-up showed that he was able to do housework and was ready to go to work. After 6 months, he was able to easily work, and his compulsive behaviour only occurred 1 to 2 times each day for about 0.5 minutes each time. Conclusions The combination of TEAS–ERP, sertraline and clomipramine had a rapid effect. There was no resumption of obsessive–compulsive symptoms during post-treatment follow-up.

Hypoxia is a predominant feature in glioblastoma (GBM) and contributes greatly to its drug resistance. However, the molecular mechanisms which are responsible for the development of the resistant phenotype of GBM under hypoxic conditions remain unclear. To analyze the key pathways promoting therapy resistance in hypoxic GBM, we utilized the U87-MG cell line as a human GBM cell model and the human brain HEB cell line as a non-neoplastic brain cell model. These cell lines were cultured in the presence of 21, 5, and 1% O2 for 24 h. We detected the changes in transcriptional profiling and analyzed the biological processes and functional interactions for the genes with different expression levels under different hypoxia conditions. The results indicated that those alterations of U87-MG cells presented specific transcriptional signature in response to diverse hypoxia levels. Gene ontology analysis revealed that the genes related to the DNA replication and cell cycle were suppressed, while the genes involved in tissue and system development to promote cancer development were activated following hypoxia. Moreover, functional interaction analysis suggested that the epigenetic regulator HDAC3 and the transcriptional factors CEBPB and JUN played a central role in organ and system developmental process pathway. Previous studies reported the global alterations caused by activation of HDAC3, CEBPB, and JUN could form the molecular basis of the resistance to chemotherapy and radiation therapy of hypoxic GBM. In our study, the significant growth inhibitory effect of temozolomide on hypoxic GBM cells could be promoted under downregulation of these genes. The experiment suggested that HDAC3, CEBPB, and JUN were closely involved in the drug-resistance phenotype of hypoxic GBM. In summary, we profiled the hypoxia-dependent changes in the transcriptome of the U87-MG cell line and the human brain cell line HEB to identify the transcriptional signatures of U87-MG cells and elucidate the role of hypoxia in the drug-resistant phenotype of GBM. Furthermore, we identified three key genes and explored their important roles in the drug resistance of hypoxic GBM.

Maize is a widely grown crop in China, and the relationships between agroclimatic parameters and maize yield are complicated, hence, accurate and timely yield prediction is challenging. Here, climate, satellite data, and meteorological indices were integrated to predict maize yield at the city-level in China from 2000 to 2015 using four machine learning approaches, e.g., cubist, random forest (RF), extreme gradient boosting (Xgboost), and support vector machine (SVM). The climate variables included the diffuse flux of photosynthetic active radiation (PDf), the diffuse flux of shortwave radiation (SDf), the direct flux of shortwave radiation (SDr), minimum temperature (Tmn), potential evapotranspiration (Pet), vapor pressure deficit (Vpd), vapor pressure (Vap), and wet day frequency (Wet). Satellite data, including the enhanced vegetation index (EVI), normalized difference vegetation index (NDVI), and adjusted vegetation index (SAVI) from the Moderate Resolution Imaging Spectroradiometer (MODIS), were used. Meteorological indices, including growing degree day (GDD), extreme degree day (EDD), and the Standardized Precipitation Evapotranspiration Index (SPEI), were used. The results showed that integrating all climate, satellite data, and meteorological indices could achieve the highest accuracy. The highest estimated correlation coefficient (R) values for the cubist, RF, SVM, and Xgboost methods were 0.828, 0.806, 0.742, and 0.758, respectively. The climate, satellite data, or meteorological indices inputs from all growth stages were essential for maize yield prediction, especially in late growth stages. R improved by about 0.126, 0.117, and 0.143 by adding climate data from the early, peak, and late-period to satellite data and meteorological indices from all stages via the four machine learning algorithms, respectively. R increased by 0.016, 0.016, and 0.017 when adding satellite data from the early, peak, and late stages to climate data and meteorological indices from all stages, respectively. R increased by 0.003, 0.032, and 0.042 when adding meteorological indices from the early, peak, and late stages to climate and satellite data from all stages, respectively. The analysis found that the spatial divergences were large and the R value in Northwest region reached 0.942, 0.904, 0.934, and 0.850 for the Cubist, RF, SVM, and Xgboost, respectively. This study highlights the advantages of using climate, satellite data, and meteorological indices for large-scale maize yield estimation with machine learning algorithms.

Mitochondria-associated membranes (MAM) are a well-recognized contact link between the mitochondria and endoplasmic reticulum that affects mitochondrial biology and vascular smooth muscle cells (VSMCs) proliferation via the regulation of mitochondrial Ca2+(Ca2+m) influx. Nogo-B receptor (NgBR) plays a vital role in proliferation, epithelial-mesenchymal transition, and chemoresistance of some tumors. Recent studies have revealed that downregulation of NgBR, which stimulates the proliferation of VSMCs, but the underlying mechanism remains unclear. Here, we investigated the role of NgBR in MAM and VSMC proliferation. We analyzed the expression of NgBR in pulmonary arteries using a rat model of hypoxic pulmonary hypertension (HPH), in which rats were subjected to normoxic recovery after hypoxia. VSMCs exposed to hypoxia and renormoxia were used to assess the alterations in NgBR expression in vitro. The effect of NgBR downregulation and overexpression on VSMC proliferation was explored. The results revealed that NgBR expression was negatively related with VSMCs proliferation. Then, MAM formation and the phosphorylation of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) was detected. We found that knockdown of NgBR resulted in MAM disruption and augmented the phosphorylation of IP3R3 through pAkt, accompanied by mitochondrial dysfunction including decreased Ca2+m, respiration and mitochondrial superoxide, increased mitochondrial membrane potential and HIF-1α nuclear localization, which were determined by confocal microscopy and Seahorse XF-96 analyzer. By contrast, NgBR overexpression attenuated IP3R3 phosphorylation and HIF-1α nuclear localization under hypoxia. These results reveal that dysregulation of NgBR promotes VSMC proliferation via MAM disruption and increased IP3R3 phosphorylation, which contribute to the decrease of Ca2+m and mitochondrial impairment.

Different kinds of radiative transfer models, including a relative sunshine-based model (BBM), a physical-based model for tropical environment (PBM), an efficient physical-based model (EPP), a look-up-table-based model (LUT), and six artificial intelligence models (AI) were introduced for modeling the daily photosynthetically-active radiation (PAR, solar radiation at 400⁻700 nm), using ground observations at twenty-nine stations, in different climatic zones and terrain features, over mainland China. The climate and terrain effects on the PAR estimates from the different PAR models have been quantitatively analyzed. The results showed that the Genetic model had overwhelmingly higher accuracy than the other models, with the lowest root mean square error (RMSE = 0.5 MJ m−2day−1), lowest mean absolute bias error (MAE = 0.326 MJ m−2day−1), and highest correlation coefficient (R = 0.972), respectively. The spatial⁻temporal variations of the annual mean PAR (APAR), in the different climate zones and terrains over mainland China, were further investigated, using the Genetic model; the PAR values in China were generally higher in summer than those in the other seasons. The Qinghai Tibetan Plateau had always been the area with the highest APAR (8.668 MJ m−2day−1), and the Sichuan Basin had always been the area with lowest APAR (4.733 MJ m−2day−1). The PAR datasets generated by the Genetic model, in this study, could be used in numerous PAR applications, with high accuracy.