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Background: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. Methods: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. Results: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). Conclusions: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

Pure waterjet surface treatment without abrasive particles has a promising application in the biomedical field, because it induces compressive residual stresses on a metal surface and never leaves the tiny hard particles. In this work, the influence of operation pressure, standoff distance and the number of paths of the waterjet on the surface topography as well as the hardness was studied using the Taguchi method. The results showed that the most essential parameter is the operation pressure. By tuning the operation pressure from 100 to 300 MPa, the surface of Ti6Al4V specimens can be smoothed, roughened or damaged; when the surface layer is eroded, the new-born surface exhibits a clear stochastic nature accompanied by microvoids. The standoff distance benefits finer controlling the height parameters, whilst the number of paths affects the waviness. The hardening effect generated by the waterjet impingement extends to a few hundred-micron depth of the specimens, and the peak value of microhardness was found at a depth of 70 μm, which is an increase by greater than 20 %. The roughness parameters of Arithmetical mean height (Sa), Skewness (Ssk), Auto-correlation length (Sal), and Developed interfacial area ratio (Sdr) as a set are recommended to characterize the biomaterial's surface. The present research results promote the application of waterjet treatment in the field of fine-tuning biomaterial surface morphology.

Objective: Skin wound exposed to complex external environment for a long time is highly susceptible to bacterial infection. Impact Statement: This work designs a Janus adhesive dual-layer hydrogel containing in situ silver nanoparticles (named PSAP/DXP@AgNPs) with integrated attack and defense to simultaneously kill the existing bacteria and prevent foreign bacterial contamination. Introduction: The current gauze dressing fixed by tape fails to well fit at skin wound and lacks intrinsic antibacterial property, making it highly prone to causing secondary infection. Moreover, foreign bacteria may contaminate the wound dressing during use, further increasing the risk of secondary infection. Methods: In this work, a Janus adhesive dual-layer PSAP/DXP@AgNPs hydrogel is prepared by sequentially building the PSAP gel layer containing zwitterionic poly(sulfobetaine methacrylamide) (PSBMA) on the DXP@AgNPs gel layer containing in situ catechol-reduced AgNPs. Results: The flexible PSAP/DXP@AgNPs can adapt shape change of skin and adhere to skin tissue with interfacial toughness of 153.38 J m−2 relying on its DXP@AgNPs layer, which is beneficial to build favorable fit. The in situ reduced AgNPs released from the DXP@AgNPs layer of PSAP/DXP@AgNPs exhibit obvious antibacterial effects against Escherichia coli and Staphylococcus aureus, with antibacterial rates of 99% and 88%, respectively. Meanwhile, the hydrated PSAP layer of PSAP/DXP@AgNPs containing PSBMA is able to prevent the bacterial contamination, decreasing the risk of secondary infection. Besides, cell experiments demonstrate that PSAP/DXP@AgNPs is biocompatible. Conclusion: The PSAP/DXP@AgNPs hydrogel with integrated attack and defense simultaneously possessing bacteria-killing and bacteria-antifouling properties is a potential alternative in treating infected skin wound.

Crowns have been recommended to treat decayed teeth and rebuild teeth function. The dental management of children with autism is a tremendous challenge for pediatric dentists due to the impaired behaviors and communication disorders. In this context, a 5-year-old boy with autism was treated to solve carious lesions under the assistance of general anesthesia. The posterior occlusal function was restored, and the crossbite existing in the primary anterior teeth was approached merely by NuSmile® zirconia crowns (ZCs) rather than orthodontic intervention. We conducted an 18-month period. Throughout the long-term follow-up, the boy’s masticatory efficiency was remarkably improved and the anterior teeth had transferred into the correct position with adequate overbite to maintain the new relationship, thus ameliorating the appearance of tissue on the labial surface and enhancing his quality of life and oral health.

Background Cadmium (Cd) is hazardous to human health because of its cytotoxicity and long biological half-life. Azoramide is a small molecular agent that targets the endoplasmic reticulum (ER) and moderates the unfolded protein response. However, its role in Cd-induced cytotoxicity remains unclear. This study was performed to investigate the protective effect of azoramide against Cd-induced cytotoxicity and elucidate its underlying mechanisms. Methods Inductively coupled plasma‒mass spectrometry was used to measure Cd concentrations in each tissue of ICR male mice. The human proximal tubule epithelial cell line HK-2 and the human retinal pigment epithelial cell line ARPE-19 were used in the in vitro study. Cell apoptosis was determined by DAPI staining, JC-1 staining, and annexin V/propidium iodide double staining. Intracellular oxidative stress was detected by MitoSOX red staining, western blot, and quantitative real-time PCR. Moreover, ER stress signaling, MAPK cascades, and autophagy signaling were analyzed by western blot. Results The present data showed that Cd accumulated in various organs of ICR mice, and the concentrations of Cd in the studied organs, from high to low, were as follows: liver > kidney > testis > lung > spleen > eye. Our study demonstrated that azoramide inhibited ER stress by promoting BiP expression and suppressing the PERK-eIF2α-CHOP pathway. Additionally, we also found that azoramide significantly decreased ER stress-associated radical oxidative species production, attenuated p38 MAPK and JNK signaling, and inhibited autophagy, thus suppressing apoptosis in HK-2 and ARPE-19 cells. Conclusion Our study investigated the effect of azoramide on Cd-induced cytotoxicity and revealed that azoramide may be a therapeutic drug for Cd poisoning.

The reasonable size of the coal pillar in the working face is usually the most critical aspect in coal mining, which is related to the deformation of the surrounding rock of the roadway and the degree of damage to the coal pillar during the coal resource extraction process. The reasonable-size design of coal pillars usually adopts methods such as strength and elastic core zone calculation. However, for the remaining coal resources, the width of the working face is often unequal, and widening or narrowing the working face can significantly change the reasonable size of the coal pillar. In the laboratory, uniaxial compression tests were conducted on coal samples with different aspect ratios. Based on the possible sizes of coal pillars in coal mines, four three-dimensional numerical models of coal pillar compression with different aspect ratios were established. Obtained the failure characteristics and strength of coal pillars with different aspect ratios and provided the strength formula and aspect ratio calculation formula for coal pillars. A mechanical roof model for widening the working face was established, and the relationship between coal pillar strength and working face width was proposed. The strength of coal pillars increases with the increase of aspect ratio. The length of the working face and the aspect ratio of the coal pillar were calculated using the coal pillar strength formula. The width of the working face has increased from 63 m to 160 m, and the size of the coal pillar has increased from 3.6 m to 13.4 m, which has improved the resource recovery rate of the coal pillar. According to the deformation monitoring of the A503 working face roadway that there is no evidence of roof caving or sheeting, and the roadway’s maximum deformation is 147.3 mm, which proves that the width of the coal pillar is suitable for the mining requirements of uneven working faces. This provides important theoretical support for reasonably determining the size of coal pillars and improving the utilisation rate of irregular coal resources.

Abstract Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell‐secreted extracellular vesicles (EVs) offer a new cell‐free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid‐derived retinal progenitor cells (hERO‐RPCs) are an easily accessible and advanced cell source for RD treatment. However, hERO‐RPCs‐derived EVs require further characterisation. Here, we compared the characteristics of EVs from hERO‐RPCs (hRPC‐EVs) with those of human embryonic stem cell (hESC)‐derived EVs (hESC‐EVs) as controls. Based on in‐depth proteomic analysis, we revealed remarkable differences between hRPC‐EVs and hESC‐EVs. A comparison between EVs and their respective cells of origin demonstrated that the protein loading of hRPC‐EVs was more selective than that of hESC‐EVs. In particular, hESC‐EVs were enriched with proteins related to angiogenesis and cell cycle, whereas hRPC‐EVs were enriched with proteins associated with immune modulation and retinal development. More importantly, compared with that of hESC‐EVs, hRPC‐EVs exhibited a lower correlation with cell proliferation and a unique capacity to regulate lipid metabolism. It was further confirmed that hRPC‐EVs potentially eliminated lipid deposits, inhibited lipotoxicity and oxidative stress, and enhanced phagocytosis and survival of oleic acid‐treated ARPE‐19 cells. Mechanistically, hRPC‐EVs are integrated into the mitochondrial network of oleic acid‐treated ARPE‐19 cells, and increased the level of mitochondrial fatty acid β‐oxidation‐related proteins. Thus, organoid‐derived hRPC‐EVs represent a promising source of cell‐free therapy for RD, especially for blinding diseases related to abnormal lipid metabolism in RPE cells.

Understanding the intricate interrelationships among ecosystem services (ESs) and exploring their driving mechanisms are prerequisites for their efficient management. The southwestern karst region is a typical ecologically fragile area and a crucial component for establishing an ecological security barrier in southern China. We aimed to evaluate the relationship between ESs and the concept of ecosystem service bundles (ESBs) and explore the distribution of ESs and their interrelationships. Using methods, such as Spearman's correlation and spatial autocorrelation analysis, this study focused on the karst peak-cluster depression region in southwestern China to analyse the trade-offs and synergistic effects among 12 ESs. Additionally, this study used the self-organizing map to identify ESBs and used the Random Forest model to explore the potential driving factors influencing the distribution patterns of ESs. The results indicated a spatial clustering effect among the 12 ESs, whereby provisioning and cultural services had the most significant clustering effect (Moran's I > 0.8). A total of 25 pairs of ESs exhibited synergistic effects, and 31 pairs showed trade-off effects. Food production showed a trade-off with both regulatory and supporting services, whereas ESs within the same category tended to exhibit synergistic effects. The distribution and interrelationships of ESs are influenced by natural and social factors, such as climate, topography, and human activities, resulting in the formation of six ESBs. This study enriches the understanding of the relationship of ESs and will contribute to the coordinated development of resources and the environment in the karst peak-cluster depression region of southwestern China.

Walnut protein-derived peptides have a variety of biological activities, but it is unclear whether walnut peptides have anti-colorectal cancer activity. Therefore, the aim of this study was to explore the anti-colorectal cancer peptides of walnut and the underlying mechanism of action by in silico analysis and in vitro evaluation. Walnut protein alcalase hydrolysate (WPH-Al) significantly inhibited the growth and induced the apoptosis of colon cancer HCT116 cells. The

ABSTRACTBiliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy. Remarkably, the patient achieved a complete response (CR) with a long-lasting survival benefit exceeding 3 years. This was achieved using a novel regimen combining SHR-1701, an anti-PD-L1/TGF-βR fusion protein, and famitinib, even though the patient had proficient mismatch repair (pMMR) and tested negative for PD-L1. Adverse events were limited and manageable. This is the first report of such a treatment regimen being applied in a clinical setting, suggesting that the SHR-1701 and famitinib combination may be a promising immunotherapeutic approach for patients with refractory advanced GBC.

IntroductionSince the outbreak of SARS-CoV-2, vaccines have demonstrated their effectiveness in resisting virus infection, reducing severity, and lowering the mortality rate in infected individuals. However, due to the rapid and ongoing mutations of SARS-CoV-2, the protective ability of many available vaccines has been challenged. Therefore, there is an urgent need for vaccines capable of eliciting potent broadly neutralizing antibodies against various SARS-CoV-2 variants.MethodsIn this study, we developed a novel subunit vaccine candidate for SARS-CoV-2 by introducing a series of shielding glycans to the Fc-fused receptor-binding domain (RBD) of the prototypic spike protein. This approach aims to mask non-neutralizing epitopes and focus the immune response on crucial neutralizing epitopes.ResultsAll modified sites were confirmed to be highly glycosylated through mass spectrometry analysis. The binding affinity of the glycan-shielded RBD (gsRBD) to the human ACE2 receptor was comparable to that of the wildtype RBD (wtRBD). Immunizing mice with gsRBD when combined with either Freund’s adjuvant or aluminum adjuvant demonstrated that the introduction of the glycan shield did not compromise the antibody-inducing ability of RBD. Importantly, the gsRBD significantly enhanced the generation of neutralizing antibodies against SARS-CoV-2 pseudoviruses compared to the wtRBD. Notably, it exhibited remarkable protective activity against Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), approximately 3-fold, 7- fold, and 17-fold higher than wtRBD, respectively.DiscussionOur data proved this multiple-epitope masking strategy as an effective approach for highly active vaccine production.

To investigate the relationship between lipid oxidation and the development of volatile compounds (VOCs) in grouper lipid during cold storage, lipids were extracted from grouper as a single-factor study to avoid the complex interactions between microorganisms and proteins. Lipid oxidation during storage and the content of 12 long-chain fatty acids (FAs) in grouper lipids were evaluated. The HS-SPME-GC–MS technique was used to analyze the VOCs in grouper lipids, and a total of 13 key VOCs, primarily comprising alcohols and aldehydes, were screened. Pearson correlation analysis showed a strong acorrelation between these 13 key VOCs, which influenced the overall flavor of grouper lipids, and lipid oxidation, mainly involving secondary oxidation of lipids and the oxidation of long-chain polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Possible solutions for grouper lipid deterioration were proposed, providing a reference for maintaining the overall quality of grouper and regulating flavor formation.

This study was aimed at preparing chitosan (CS)-phenolic acids copolymers to obtain better preservation effect in marine products. In this work, CS was grafted onto phenolic acids such as gallic acid (GA) and protocatechuic acid (PA) by a carbodiimide coupling method. The copolymers (CS-grafted-GA (CS-g-GA) and CS-grafted-PA (CS-g-PA)) were further confirmed through physicochemical properties including ultraviolet–visible (UV–Vis) spectrophotography, fourier transform infrared (FTIR) spectrometry, differential scanning calorimetry (DSC) thermogram, rheological behaviour, scanning electron microscope (SEM) and antioxidant activity analysis. Subsequently, the effects of copolymers on preservation of refrigerated sea bass (Lateolabrax japonicus) fillets were investigated. The results showed that the CS-g-GA (110.82 mg GA/g) exhibited higher grafting rate than CS-g-PA (62.63 mg PA/g). According to the assessment of UV–Vis and FTIR spectrometry, both the GA and PA were grafted onto CS successfully. SEM analysis demonstrated that the microstructure of copolymers became irregular. Meanwhile, both the CS-g-GA and CS-g-PA copolymers displayed superior thermal stability, rheological properties and antioxidant capacity than the pure CS. Furthermore, the copolymers also revealed a significantly stronger preservation effect on sea bass fillets including inhibiting microbial growth and delaying the deterioration of color, texture and sensory quality. Therefore, CS-g-GA and CS-g-PA could be used as promising preservatives for seafood.

In this study, the effects of cellulase addition, ethanol volume fraction, cellulase digestion time and ultrasound time on the extraction rate of Moringa oleifera seeds polyphenols were investigated. At the same time, the extraction process of Moringa oleifera seeds polyphenols by ultrasound-assisted cellulase method was optimized using response surface methodology. In addition, the in vitro antioxidant and hypoglycemic and hypolipidemic activities of Moringa oleifera seeds polyphenols were also investigated. The results showed that the optimal process for the extraction of Moringa oleifera seed polyphenols by ultrasound-assisted cellulase was 0.30% enzyme addition, 53.00% volume fraction of ethanol, 31.00 min enzymatic digestion time, and 31.00 min ultrasound time. Under this process condition, the amount of Moringa oleifera seed polyphenols extracted obtained was 6.90 mg/g, which was not significantly different from the predicted value. In addition, the study found that Moringa oleifera seed polyphenols had good antioxidant activity, and its IC50 for scavenging ABTS radicals and DPPH radicals were 0.76 and 0.61 mg/mL, respectively. Meanwhile, Moringa oleifera seed polyphenols had some pancreatic lipase and α-amylase inhibitory activities, and theirs IC50 for pancreatic lipase and α-amylase inhibition rate were 1.35 and 6.55 mg/mL, respectively. This study provides a theoretical basis for the extraction and application of Moringa oleifera seed polyphenols.

In this work, five novel Ti- and TiZr-based high entropy bulk metallic glasses (HE-BMGs) with good glass forming ability (GFA) were developed, among which the (Ti37.31Zr22.75Be26.39Al4.55Cu9)94Ni6 alloy possesses the largest critical diameter of 9 mm. All developed HE-BMGs exhibit high yield strength and good compressive plasticity at room temperature. Especially, the (Ti37.31Zr22.75Be26.39Al4.55Cu9)94Co6 alloy with large GFA has suitable density and high specific strength (3.90 × 105 N m/kg), showing great potential in the aerospace sector. Moreover, the activation energies at characteristic temperatures of three HE-BMGs were obtained using the Kissinger method. The local Avrami exponents were calculated to analyze the crystallization mechanism of these HE-BMGs, revealing that the first crystallization process is mostly dominated by diffusion-controlled three-dimensional growth of pre-existing nuclei. In addition, all three HE-BMGs can be classified as “intermediate glasses” according to their fragility index values.

Abstract Background The purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery. Methods This revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed. Results All patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation. Conclusions Merit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.

Abstract The Xiangjiang River Basin is an important part of the Yangtze River Basin and an important area in Hunan Province. Thus, taking steps to protect the ecological sustainability of the Xiangjiang River Basin, such as the construction of the protection of ecological security in Hunan Province and the Yangtze River Protection Law, is important for national projects However, research on the ecological quality of the Xiangjiang River Basin is mostly biased toward the evaluation of ecosystem services or an individual ecological index. Furthermore, a long-term evaluation of multiple indicators is lacking. Therefore, based on Google Earth Engine and geographic detectors, the remote sensing ecological index was used to evaluate this area. The year-by-year research on the Xiangjiang River Basin from 2001 to 2020 clarified its past ecological quality change trend, explored the reasons for the ecological quality change, and provided a basis for protecting its ecological quality. The following results are presented. (1) Regarding spatial distribution, areas with poor ecological environments are mainly distributed at the centers of Chang-Zhu-Tan, Hengyang, and various districts and counties. (2) Regarding the time variation, the ecological quality of the Xiangjiang River Basin from 2001 to 2020 showed a slight downward trend, with a downward slope of approximately − 0.0000357143; a rapid increase, with a growth rate of approximately 0.00395; And an overall improvement over 20 years. The areas with declining ecological quality are mainly located in the Chang-Zhu-Tan urban agglomeration, the city center of Hengyang, and the county centers of various county towns. (3) The factor detection results show that human factors play a key role in population density and land use, with average q values of 0.429 and 0.353, respectively. Among natural factors, elevation and slope play a key role, with average q values of 0.230 and 0.351, respectively; hence, Land use directly affect on the ecological quality in a location. These findings will provide important information for managers to formulate ecological restoration measures for the Xiangjiang River.

Abstract Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged

Abstract Fibroblast growth factor 19 (FGF19) is recognized to play an essential role in cartilage development and physiology, and has emerged as a potential therapeutic target for skeletal metabolic diseases. However, FGF19-mediated cellular behavior in chondrocytes remains a big challenge. In the current study, we aimed to investigate the role of FGF19 on chondrocytes by characterizing mitochondrial biogenesis and fission–fusion dynamic equilibrium and exploring the underlying mechanism. We first found that FGF19 enhanced mitochondrial biogenesis in chondrocytes with the help of β Klotho (KLB), a vital accessory protein for assisting the binding of FGF19 to its receptor, and the enhanced biogenesis accompanied with a fusion of mitochondria, reflecting in the elongation of individual mitochondria and the up-regulation of mitochondrial fusion proteins. We then revealed that FGF19-mediated mitochondrial biogenesis and fusion required the binding of FGF19 to the membrane receptor, FGFR4, and the activation of AMP-activated protein kinase alpha (AMPKα)/peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)/sirtuin 1 (SIRT1) axis. Finally, we demonstrated that FGF19-mediated mitochondrial biogenesis and fusion was mainly dependent on the activation of p-p38 signaling. Inhibition of p38 signaling largely reduced the high expression of AMPKα/PGC-1α/SIRT1 axis, decreased the up-regulation of mitochondrial fusion proteins and impaired the enhancement of mitochondrial network morphology in chondrocytes induced by FGF19. Taking together, our results indicate that FGF19 could increase mitochondrial biogenesis and fusion via AMPKα-p38/MAPK signaling, which enlarge the understanding of FGF19 on chondrocyte metabolism. Video Abstract

The effectiveness of COVID-19 vaccines depends on widespread vaccine uptake. Employing a telephone-administered weighted survey with 19,502 participants, we examined the determinants of COVID-19 vaccine acceptance among adults in Texas. We used multiple regression analysis with LASSO-selected variables to identify factors associated with COVID-19 vaccine uptake and intentions to receive the vaccine among the unvaccinated. The prevalence of unvaccinated individuals (22%) was higher among those aged 18–39, males, White respondents, English speakers, uninsured individuals, those facing financial challenges, and individuals expressing no concern about contracting the illness. In a fully adjusted regression model, higher odds of being unvaccinated were observed among males (aOR 1.11), the uninsured (aOR 1.38), smokers (aOR 1.56), and those facing financial struggles (aOR 1.62). Conversely, Asians, Blacks, and Hispanics were less likely to be unvaccinated compared to Whites. Among the unvaccinated, factors associated with stronger intent to receive the vaccine included age (over 65 years), Black and Hispanic ethnicity, and perceived risk of infection. Hispanic individuals, the uninsured, those covered by public insurance, and those facing financial challenges were more likely to encounter barriers to vaccine receipt. These findings underscore the importance of devising tailored strategies, emphasizing nuanced approaches that account for demographic, socioeconomic, and attitudinal factors in vaccine distribution and public health interventions.

The COVID-19 vaccine is safe and effective for children, yet parental hesitancy towards vaccinating children against the virus persists. We conducted a telephone-administered weighted survey in Texas to examine parents’ sociodemographic factors and medical conditions associated with COVID-19 vaccination intention for parents with unvaccinated children ages 5–17 years. We collected responses from 19,502 participants, of which 4879 were parents of children ages 5–17 years. We conducted multiple logistic regression with Lasso-selected variables to identify factors associated with children’s vaccination status and parents’ intention to vaccinate their children. From the unweighted sample, less than half of the parents (46.8%) had at least one unvaccinated child. These parents were more likely to be White, English-speaking, not concerned about illness, privately insured, and unvaccinated for COVID-19 themselves (p < 0.001). In the adjusted regression model, parents who were unvaccinated (vs. having COVID-19 booster, aOR = 28.6) and financially insecure (aOR = 1.46) had higher odds of having unvaccinated children. Parents who were Asian (aOR = 0.50), Black (aOR = 0.69), Spanish-speaking (aOR = 0.57), concerned about illness (aOR = 0.63), had heart disease (aOR = 0.41), and diabetes (aOR = 0.61) had lower odds of having unvaccinated children. Parents who were Asian, Black, Hispanic, Spanish-speaking, concerned about illness for others, and vaccine-boosted were more likely to have vaccination intention for their children (p < 0.001). Children’s vaccination is essential to reduce COVID-19 transmission. It is important to raise awareness about the value of pediatric COVID-19 vaccination while considering parents’ sociodemographic and medical circumstances.

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus’s pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine–cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity.

The matrix material used in this paper was low-density polyethene (LDPE), and the added particles selected were silicon oxide (SiO2) particles and montmorillonite (MMT) particles. The sizes of the SiO2 particles were 1 µm, 30 nm, and 100 nm, respectively; three kinds of SiO2/MMT/LDPE multi-component composites were prepared based on MMT/LDPE composites doped with MMT particles. The effect of the SiO2 particle size on the crystallization behavior and space charge properties of SiO2/MMT/LDPE composites was studied. The crystalline behaviors and crystallinity of the materials were analyzed. At the same time, the changes in the relative dielectric constant εr and loss factor tanδ for each material with the influence of frequency were studied, and the space charge accumulation, residual characteristics, and apparent charge mobility of each material were explored. The results show that the smaller the size of the added particles, the smaller the grain size and the clearer the grain outline for the multi-composite material. After adding 30 nm SiO2 particles, the crystallinity of the material increases significantly. The microstructure formed by the addition of 100 nm SiO2 particles effectively restricts molecular chain movement and makes it difficult to establish the polarization of the composite. The incorporation of large-size particles can reduce the proportion of the crystalline structure for the material as a whole, resulting in the formation of a new structure to promote charge transfer. Among the three kinds of SiO2 particles, the addition of 30 nm SiO2 particles can effectively suppress the space charge, and the composite material has the lowest residual space charge after depolarization. The addition of 100 nm SiO2 particles can cause the accumulation of many homopolar charges near the anode.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible airflow obstruction with abnormal lung function. Because its pathogenesis involves multiple aspects of oxidative stress, immunity and inflammation, apoptosis, airway and lung repair and destruction, the clinical approach to COPD treatment is not further updated. Therefore, it is crucial to discover a new means of COPD diagnosis and treatment. COPD etiology is associated with complex interactions between environmental and genetic determinants. Numerous genes are involved in the pathogenic process of this illness in research samples exposed to hazardous environmental conditions. Among them, Long non-coding RNAs (lncRNAs) have been reported to be involved in the molecular mechanisms of COPD development induced by different environmental exposures and genetic susceptibility encounters, and some potential lncRNA biomarkers have been identified as early diagnostic, disease course determination, and therapeutic targets for COPD. In this review, we summarize the expression profiles of the reported lncRNAs that have been reported in COPD studies related to environmental risk factors such as smoking and air pollution exposure and provided an overview of the roles of those lncRNAs in the pathogenesis of the disease.

BackgroundInflammatory bowel disease (IBD) is a chronic immune-mediated disorder affecting millions worldwide. Due to the complexity of its pathogenesis, the treatment options for IBD are limited. This study focuses on ELF4, a member of the ETS transcription factor family, as a target to elucidate its role in IBD and investigate its mechanism of action in alleviating IBD symptoms by activating IL1RN transcription to suppress the activity of inflammatory TH17 cells.MethodsUsing the GEO database, this study examined LPS-induced intestinal inflammatory genes and their regulation mechanisms. We examined the colon length of LPS-treated mice and derived the Disease Activity Index (DAI). H&E staining, ELISA, and flow cytometry were used to detect mice colon tissue damage, inflammatory factor levels in mouse serum, mouse macrophage types and inflammatory TH17 cell activity. RT-qPCR and Western blot detected ELF4, IL1RN, M1, and M2 polarization markers. In Vitro, using dual-luciferase and ChIP assays, we tested mouse bone marrow-derived macrophages (BMDMs) and mouse intestinal epithelial cells for IL1RN promoter activity and ELF4 enrichment.ResultsBioinformatics showed that LPS-induced colitis animals have reduced ELF4 expression in their colon tissue. In vivo tests confirmed reduced ELF4 expression in mice with LPS-induced colitis. ELF4 overexpression reduced mouse intestinal inflammation. ELF4 activated IL1RN transcription in bioinformatics and in vitro tests. ELF4 promoted IL1RN transcription and macrophage M2 polarization to limit intestinal epithelial cell death and inflammation and reduce mouse intestinal inflammation in vitro. ELF4 also reduced the Th17/Treg ratio by increasing IL1RN transcription.ConclusionELF4 activates IL1RN transcription, suppresses inflammatory TH17 cells, and induces macrophage M2 polarization to treat IBD.

With the rapid development of economy and urbanization in China, cities are expanding rapidly and more constructions are being built, then lead to the fast-growing part in urban residential energy consumption. In China’s hot summer and cold winter regions, many buildings are not centrally heated and commonly rely on electrical equipment such as air conditioners which are all energy-inefficient thermoregulation devices. In order to analyze the relationship between building energy consumption and the energy efficiency ratio (EER) of air conditioning and the area of photovoltaic (PV) on the roof, the influence of the building envelope on building energy consumption in hot summer and cold winter regions in China is clarified. This paper uses energy plus software to analyze the impact of different EER and PV area on building energy consumption using a typical case study of a public health upgrading project in the eastern part of the Wuxing district, Huzhou, Zhejiang province in China. The simulation results show that the factor that has a greater impact on the energy consumption of the health center in summer is the PV area parameter of the building compared to the performance parameters of the air conditioning equipment. The PV area parameter settings and air conditioning equipment performance adjustments are dependent on the actual situation and the comprehensive energy saving rate of the outpatient building for public health in the eastern part of Tai Wu Xing District can exceed 50%. Finally, an economic analysis of the carbon tax and input costs is carried out, and the best combination is of which 60% of the area covered by Longi Green PV panels and an air conditioning efficiency ratio of 4.87. The research result combines renewable energy and efficient equipment to achieve dual optimization of environmental and economic aspects of building energy consumption, while providing reference opinions on the comprehensive evaluation method of building energy consumption from the perspective of carbon tax.

Deoxycholate (DA) is a natural emulsifying agent involved in the absorption of dietary lipids. Due to the facial distribution of hydrophobic-hydrophilic region, DA easily aggregates under ambient conditions, and this property hinders the practical application of DA in clinical applications. In this study, we found that the molecular arrangement of DA molecules could be controlled by using layered double hydroxide (LDH) under a specific reaction condition. The effect of reaction methods such as co-precipitation, ion exchange and reconstruction on the molecular arrangement of DA was investigated by X-ray diffraction, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy and differential scanning calorimetry. It was demonstrated that the self-aggregation of DA molecules could be suppressed by the oriented arrangement of DA between the gallery space of LDH. The DA moiety was well stabilized in the LDH layers due to the electrostatic interaction between DA molecules and LDH layers. The most ordered arrangement of DA molecules was observed when DA was incorporated into LDH via a reconstruction method. The DA molecules arranged in LDH via reconstruction did not show significant exothermic or endothermic behaviour up to 400°C, showing that the DA moiety lost its intermolecular attraction in between LDH layers.

BackgroundDiabetic retinopathy (DR) is a common complication of diabetes. The adipocytokines are closely associated with the occurrence and development of diabetes and its related complications. Literature confirms that the level of adiponectin in patients with DR is significantly higher; however, the relationship between other adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR remains unclear.AimThis study aimed to systematically evaluate the association between adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR.MethodsThe PubMed, Web of Science, Embase, EBSCO and Willy databases were used to search for potential studies with keywords such as “diabetic retinopathy” or “DR” in combination with the terms “leptin,” “chemerin”, “apelin” or “omentin-1” in the search titles or abstracts. Standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were determined as the results of the meta-analysis.ResultsAfter screening, 18 articles were included in the meta-analysis including 750 DR cases and 993 controls. Leptin and chemerin levels in patients with DR were significantly higher than those in the control group (SMD: 0.68, 95% CI [0.1, 1.26]; SMD: 0.79, 95% CI [0.35, 1.23]). The omentin-1 levels in patients with DR were significantly lower than those in the controls (SMD: –0.85, 95% CI [–1.08, –0.62]).ConclusionsTo the best of our knowledge, this is the first meta-analysis to evaluate the leptin, chemerin, apelin, and omentin-1 levels in patients with DR. Further high-quality studies are warranted to support the association between these adipocytokines and DR.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=443770, identifier CRD42023443770.

IntroductionChronic spontaneous urticaria (CSU) is a common skin condition that can significantly impact patients’ quality of life. Although studies have demonstrated the efficacy of acupuncture in treating CSU, the underlying mechanisms remain unclear. Dysfunction within the brain’s default mode network (DMN) represents a fundamental characteristic of central pathological changes associated with CSU. Therefore, it is hypothesized that improving brain network dysfunction could serve as a key mechanism through which acupuncture exerts its therapeutic effects. This study aims to provide evidence supporting this hypothesis.Methods and analysisThis study, a parallel, randomized, sham-controlled functional neuroimaging investigation will be conducted in China. We aim to enroll 50 patients with CSU and 25 healthy controls, distributing them evenly between the acupuncture and sham acupuncture groups in a 1:1 ratio. The total observation period will span 6 weeks, including 2 weeks designated for the baseline phase and 4 weeks allocated for the clinical treatment phase. Prior to treatment, all participants will undergo magnetic resonance scanning, clinical index detection, and microbiota collection. Following treatment, the patients with CSU will be retested for these indicators. Using resting-state functional connectivity (rsFC) analysis, dynamic Functional Connection (dFC) analysis, and brain microstate extraction technology combined with correlation analysis of microbiota and clinical indicators, the regulatory mechanism of acupuncture on the brain network of CSU will be evaluated from multiple dimensions.Ethics and disseminationThis trial was approved by the Biomedical Ethics Review Committee of the West China Hospital, Sichuan University (No. 2022-1255). Each participant will provide written informed consent to publish any potentially identifiable images or data.Clinical trial registrationhttps://www.chictr.org.cn/, identifier: ChiCTR2200064563.

Spinach is also known as Persian cuisine, it is rich in nutrients such as protein, vitamin C and minerals, and has high nutritional value. In this study, Spinach was treated with melatonin in order to prolong its shelf life. Melatonin has strong antioxidant effects as an endogenous free radical scavenger. The spinach was sprayed with 0.10, 0.20 and 0.30 mg/mL melatonin solution after harvesting, and distilled water was used as control for low temperature storage at 4 °C. The results showed that melatonin spraying Spinach delayed the degradation of chlorophyll, especially the treatment of 0.20 mg/mL melatonin was the most effective. The content of soluble sugar and soluble protein in spinach tissue was kept high, the accumulation of malondialdehyde (MDA) was reduced, and the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were increased. These findings suggested that melatonin treatment may be a useful technique to prolong the postharvest life of spinach and improve its quality.

In large urban agglomerations with fragmented landscapes, the relationship between habitat quality driving mechanisms and county ecological network weights has not yet been revealed. This study investigated the metropolitan area of Changsha-Zhuzhou-Xiangtan urban agglomeration (CZXUA), focusing on birds, and modified the habitat quality model with Normalised Difference Vegetation Index (NDVI), to explore the contribution of factors to the spatial heterogeneity of bird habitat quality (HQb) and the driving force at global and local scales. Ecological networks were identified based on appropriate distance thresholds, and county weight was calculated based on the gravity model. The results showed that: (1) at the global scale, the contribution of human disturbance to the spatial heterogeneity of HQb continued to increase, up to 73 %. All factors showed non-linear driving effects. The global fit of landscape pattern factors was low, suggesting local linear regression relationships. Mosaic filling-induced habitat quality improvement depends on the trade-offs between the patch spacing and the penetration degree of different patches. (2) Ecological network showed source degradation, corridor fragmentation, and out-migration over time. The interaction between Xiangtan County and Lukou District decreased from 1,357,145 to 896,077, while the interaction between Xiangtan and Changsha County increased slightly from 99,035 to 107,641. Landscape fragmentation was the direct cause of the decrease in weight, while source geocentric transfer was the indirect cause. (3) Habitat quality can be an explicit indicator, while ecological network weight was a constantly fluctuating implicit indicator. A county may acquire ecological sources from more degraded neighbouring counties and become a new ecological network hub. It is important to evaluate the changes in the weighting of the counties at a large scale, so as to determine their vulnerability as habitat spaces and the likelihood of being threatened by the factors affecting them, and to avoid neglecting the ecological network benefits due to the fragmentation of county habitats. These findings could provide suggestions for ecological restoration and connectivity strategies in urban agglomerations.

Research on ecological network of highly urbanised areas still suffers from a lack of species specificity in the identification of sources and corridors, solidified identification range with errors, and neglect of stepping stones. This study examined the evolution of ecological network components (habitats and corridors) of the active urban birds, with factors that impact them, from the perspective of functional performance, with the aim of evaluating ecological networks using a flexible identification approach. Habitat function performance (level of ecological source function performance, SFP; level of ecological stepping-stone function performance, SsFP) and corridor function performance (CFP) per grid were constructed using a flexible identification strategy to ensure that the ecological network function of each grid was not overlooked. Additionally, nonlinear relationships between bird habitats in ecological network components and three driving factor types such as topography, resistance, and landscape pattern were explored at the global scale using the Moran’s I, geographical detector, and regression equations. Local regressions were used to determine the impact of regional landscape patterns on CFP for management recommendations. The following results were observed: (1) Of the 238 grids with significant continuous changes in SFP and SsFP, scenario 16 (S16: SFP continuously decreasing with SsFP continuously increasing) accounted for 33.40%, indicating more grids had a transfer in primary function performance from source to stepping stones, mainly in the central part of Changsha-Zhuzhou-Xiangtan urban agglomeration (CZXUA). The amount of change in the continuous change scenario was concentrated within the range 0.2–0.6. (2) Spatial correlation analysis showed that the positive indicators, percentage of construction land (CLP) and nighttime lighting data (NLD), and the negative indicator, normalised difference vegetation index (NDVI), in resistance had consistently increasing negative and positive correlations with SFP, whereas the correlations with the landscape pattern indices remained stable. Topography and resistance factors contributed more to the spatial heterogeneity of SFP, whereas their contribution to SsFP demonstrated the opposite trend. The regression relationship between habitat function performance and explanatory variables showed a high R2 value for nonlinear fitting. (3) Multiscale CFP was identified based on habitat function and the contribution of resistance factors. Geographically weighted regression analysis showed significant positive and negative impacts on CFP at the local scale, with landscape diversity and patchy irregularities providing more spaces for potential ecological corridor functions, and that regional landscape regulation strategies need to be weighed from multiple perspectives. Overall, this study proposes a flexible method for identifying ecological networks and multi-scale urban ecological management strategies.

Objectives: The degree of endolymphatic hydrops in Meniere's disease may be related to hearing loss. However, the results of prior studies have been inconsistent. We aimed to investigate the relationship between endolymphatic hydrops and hearing loss characteristics in Meniere’s disease. Methods: This study included 54 patients (62 ears) with Meniere’s disease. Patients underwent three-dimensional real inversion recovery sequences for magnetic resonance imaging and pure-tone audiometry. Endolymphatic hydrops were assessed according to Gurkov’s criteria (2011). Correlations between different degrees of endolymphatic hydrops and pure-tone audiometry, as well as staging, were analysed. Results: Pure tone audiometry and staging were higher for vestibular endolymphatic hydrops complicated by cochlear ones than isolated cochlear or vestibular hydrops (both p 0.05). The degree of hydrops in the middle turn was correlated with the mid-frequency hearing threshold (p

BackgroundThe management of atrial fibrillation (AF) with oral anticoagulants (OAC) is generally recommended to reduce the risk of stroke. However, the decision to prescribe these medications for patients with AF and dementia remains controversial.MethodsA systematic review and meta-analysis of retrospective cohort studies were conducted. The search encompassed PubMed, Cochrane Library, Web of Science, and Embase databases from inception until May 1st, 2023, with language limited to English. Eligible studies included comparisons between exposure to OAC vs. non-OAC in the AF population with dementia or cognitive impairment. Studies that compared the effects of direct oral anticoagulants (DOAC) and vitamin-K antagonists were also included. The primary outcome was all-cause mortality, and the secondary outcomes were ischemic stroke and major bleeding. This study was registered with PROSPERO (No. CRD42023420678).ResultsA total of five studies (N = 21,962 patients) met the eligibility criteria and were included in this review. The follow-up duration ranged from 1 to 4 years. Meta-analysis demonstrated that OAC treatment was associated with a lower risk of all-cause mortality in AF patients with dementia with a hazard ratio (HR) of 0.79 and a 95% confidence interval (CI) ranging from 0.68 to 0.92, compared to non-OAC treatment. No statistical differences were observed in the risk of major bleeding (HR = 1.12, 95% CI: 0.88–1.42) or ischemic stroke (HR = 0.77, 95% CI: 0.58–1.00). Three studies reported comparisons between DOAC and warfarin; however, pooled analysis was not performed due to heterogeneity.ConclusionThe use of OACs in individuals diagnosed with both AF and dementia holds the potential to reduce all-cause mortality rates, thereby improving the overall clinical prognosis within this specific population.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420678, PROSPERO identifier, CRD42023420678.

Mycelium bio-composites was developed by incubating Pleurotus ostreatus fungi on different substrates from agricultural residual byproducts, including rice straw, bagasse, coir-pith, sawdust, and corn straw. The scanning electron microscope (SEM) results showed that the hypha of composite derived from bagasse was the densest, and the diameter of hypha was the biggest (0.77 µm), which was presumably due to the existence of cellulose in bagasse in the form of dextran and xylan. The maximum and minimum compression strength for sawdust substrate and corn straw substrate were 456.70 and 270.31 kPa, respectively. The flexural strength for bagasse substrate and rice straw substrate were 0.54 and 0.16 MPa, respectively. The two composites derived from rice straw and bagasse exhibited higher hydrophobic properties than others. In comparison, mycelium bio-composite derived from bagasse showed the best comprehensive properties. Except for a little worse anti-creep ability and waterproof performance, other properties of mycelium bio-composites could be comparable to commercially expanded polystyrene (EPS) packaging material. Derived from this study, mycelium material provided a good way to use agricultural residual byproducts and could be a good alternative to non-biodegradable materials for packaging applications.

Abstract This paper provides comprehensive experimental analysis relating to improvements in the two-dimensional (2D) p-type metal–oxide–semiconductor (PMOS) field effect transistors (FETs) by pure van der Waals (vdW) contacts on few-layer tungsten diselenide (WSe2) with high-k metal gate (HKMG) stacks. Our analysis shows that standard metallization techniques (e.g., e-beam evaporation at moderate pressure ~ 10–5 torr) results in significant Fermi-level pinning, but Schottky barrier heights (SBH) remain small (

Abstract Purpose The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects. Methods A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group. Results The Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00–125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively. Conclusion Two Oseltamivir phosphate for suspensions are safe and bioequivalent.

Abstract Background Gut microbiota plays a critical role in the onset and development of depression, but the underlying molecular mechanisms are unclear. This study was conducted to observe the characteristics of gut microbiota, lipid metabolism and neurotransmitters in Gut-Liver-Brain axis in depressed mice (DM), and identify some novel perceptions on relationships between gut microbiota and depression. Methods A mouse model of depression was built used chronic unpredictable mild stress (CUMS). Fecal samples (measuring gut microbiota compositions, microbial genes and lipid metabolites), liver samples (measuring lipid metabolites), and hippocampus (measuring neurotransmitters) were collected. Both univariate and multivariate statistical analyses were used to identify the differential gut microbiota, metabolic signatures and neurotransmitters in DM. Results There were significant differences on both microbial and metabolic signatures between DM and control mice (CM): 71 significantly changed operational taxonomic units (OTUs) (60.56% belonged to phylum Firmicutes) and 405 differential lipid metabolites (51.11% belonged to Glycerophospholipid (GP) metabolism) were identified. Functional analysis showed that depressive-like behaviors (DLB)-related differential microbial genes were mainly enriched in GP metabolism. Weighted correlation network analysis (WGCNA) showed that DLB-related differential metabolites mainly belonged to GPs. Meanwhile, seven differential neurotransmitters were identified. Comprehensive analysis found that Lachnospiraceae and gamma-aminobutyric acid (GABA) were significantly correlated with 94.20% and 53.14% differential GPs, respectively, and GABA was significantly correlated with three main DLB phenotypes. Conclusion Our results provided novel perceptions on the role of Gut-Liver-Brain axis in the onset of depression, and showed that GP metabolism might be the bridge between gut microbiota and depression. “Lachnospiraceae-GP metabolism-GABA” held the promise as a potential way between gut microbiota and brain functions in DM.

Background & Aims: Observational epidemiologic studies have associated vitamin D deficiency with cholestasis. We reported previously that activation of the vitamin D/vitamin D receptor (VDR) axis in cholangiocytes mitigates cholestatic liver injury by remodeling the damaged bile duct. However, the function of VDR in hepatocytes during cholestasis remains unclear. Methods: Paricalcitol (VDR agonist, 200 ng/kg) was injected intraperitoneally into bile duct–ligated mice every other day for 5 days. Primary hepatocytes and HepG2 hepatoma cells were transfected with Vdr short hairpin RNA, control short hairpin RNA, Vdr plasmid, control vector, Atg5 small interfering RNA (siRNA), and control siRNA. Liver histology, cell proliferation, and autophagy were evaluated. Results: Treatment with the VDR agonist paricalcitol improved liver injury in bile duct–ligated mice by up-regulating VDR expression in hepatocytes, which in turn reduced hepatocyte apoptosis by inhibiting reactive oxygen species (ROS) generation via suppressing the Ras-related C3 botulinum toxin substrate 1/reduced nicotinamide adenine dinucleotide phosphate oxidase 1 pathway. Mechanistically, upon exposure to an ROS-inducing compound, Vdr siRNA contributed to apoptosis, whereas the Vdr overexpression caused resistance to apoptosis. Interestingly, up-regulated VDR expression also increased the generation of autophagosomes and macroautophagic/autophagic flux, which was the underlying mechanism for reduced apoptosis following VDR activation. Autophagy depletion impaired the positive effects of VDR overexpression, whereas autophagy induction was synergystic with VDR overexpression. Importantly, up-regulation of VDR promoted autophagy activation by suppressing the activation of the extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase (p38MAPK) pathway. Thus, a p38MAPK inhibitor abrogated the Vdr siRNA-induced decrease in autophagy and the Vdr siRNA-induced increase in apoptosis. In contrast, a Mitogen-activated protein kinase kinase (MEK)/ERK activator prevented the enhancement of autophagy and decreased apoptosis following Vdr overexpression. Moreover, the ROS inhibitor N-acetylcystein (NAC) blocked Vdr siRNA-enhanced activation of the ERK/p38MAPK pathway. Conclusions: VDR activation mitigated liver cholestatic injury by reducing autophagy-dependent hepatocyte apoptosis and suppressing the activation of the ROS-dependent ERK/p38MAPK pathway. Thus, VDR activation may be a potential target for the treatment of cholestatic liver disease.

The internal mechanism of the high hydrophobicity of the coal samples from the Pingdingshan mining area was studied through industrial, element, and surface functional group analysis. Laboratory testing and molecular dynamics simulations were employed to study the impact of three types of surfactants on the surface adsorption properties and wettability of highly hydrophobic bituminous coal. The results show that the surface of highly hydrophobic bituminous coal is compact, rich in inorganic minerals, and poorly wettable and that coal molecules are dominated by hydrophobic functional groups of aromatic rings and aliphatic structures. The wetting performance of surfactants as the intermediate carrier to connect coal and water molecules is largely determined by the interaction force between surfactants and coal (Fs-c) and the interaction force between surfactants and water (Fs-w), which effectively improve the wettability of modified coal dust via modifying its surface electrical properties and surface energy. A new type of wetting agent with a dust removal rate of 89% has been developed through discovery of a compound wetting agent solution with optimal wetting and settling performance. This paper provides theoretical and technical support for removing highly hydrophobic bituminous coal dust in underground mining.

Highlights An efficient and general strategy for ultrafast synthesis of seven transition metal layered hydroxides on conductive substrates is proposed, which avoids the use of additional reagents, multiple steps and long production time in the traditional bottom-up method. The whole synthesis process only takes as fast as approximately 13 s, and its synthesis rate reaches ~ 0.46 cm2 s−1. The NiCo LDH@CC as a demonstration example is selected as cathode material for aqueous alkaline Zn (micro-) battery, which exhibits an outstanding performance.

Abstract Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-β3), a vital member of the highly conserved TGF-β superfamily, plays a versatile role in cartilage physiology and pathology. TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-β3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.

Landform classification, which is a key topic of geography, is of great significance to a wide range of fields including human construction, geological structure research, environmental governance, etc. Previous studies of landform classification generally paid attention to the topographic or texture information, whilst the watershed spatial structure has not been used. This study developed a new landform classification method based on watershed geospatial structure. Via abstracting the landform into the internal and marginal structure, we adopted the gully weighted complex network (GWCN) and watershed boundary profile (WBP) to simulate the watershed geospatial structure. Introducing various indices to quantitatively depict the watershed geospatial structure, we conducted the landform classification on the Northern Shaanxi of Loess Plateau with a watershed-based strategy and established the classification map. The classified landform distribution has significant spatial aggregation and clear regional boundaries. Classification accuracy reached 89% and the kappa coefficient reached 0.87%. Besides, the proposed method has a positive response to some similar and complex landforms. In general, the present study first utilized the watershed geospatial structure to conduct landform classification and is an efficient landform classification method with well accuracy and universality, offering additional insights for landform classification and mapping.

Abstract Background Tumor glycolysis is a critical event for tumor progression. Docetaxel is widely used as a first-line drug for chemotherapy and shown to have a survival advantage. However, the role of docetaxel in tumor glycolysis remained poorly understood. Methods The effect of Docetaxel in tumor glycolysis and proliferation were performed by CCK-8, Western blotting, real-time PCR, glucose, and lactate detection and IHC. ChIP and luciferase assay were used to analyze the mechanism of Docetaxel on Smad3-mediated HIF-1α transactivity. Results In this study, we showed that docetaxel treatment led to a significant inhibition of cell proliferation in prostate cancer cells through PFKP-mediated glycolysis. Addition of lactate, a production of glycolysis, could reverse the inhibitory effect of docetaxel on cell proliferation. Further analysis has demonstrated that phosphorylation of Smad3 (Ser213) was drastically decreased in response to docetaxel stimulation, leading to reduce Smad3 nuclear translocation. Luciferase and Chromatin immunoprecipitation (ChIP) analysis revealed that docetaxel treatment inhibited the binding of Smad3 to the promoter of the HIF-1α gene, suppressing transcriptional activation of HIF-1α. Moreover, ectopic expression of Smad3 in prostate cancer cells could overcome the decreased HIF-1α expression and its target gene PFKP caused by docetaxel treatment. Most importantly, endogenous Smad3 regulated and interacted with HIF-1α, and this interaction was destroyed in response to docetaxel treatment. What’s more, both HIF-1α and PFKP expression were significantly reduced in prostate cancer received docetaxel treatment in vivo. Conclusion These findings extended the essential role of docetaxel and revealed that docetaxel inhibited cell proliferation by targeting Smad3/HIF-1α signaling-mediated tumor Warburg in prostate cancer cells. Video Abstract

Abstract Background Patients with systemic lupus erythematosus (SLE) suffer from a high incidence of premature ovarian failure, which might be due to cyclophosphamide gonadal toxicity, immune abnormalities, or other reasons. This study aimed to investigate whether the transplantation of human umbilical cord mesenchymal stem cells (HUC‐MSCs) can improve ovarian reserve function in lupus mice. Methods We used MRL/lpr mice to observe changes in ovarian structure and secretory function in SLE. Lupus mice and controls were injected with HUC‐MSCs at Weeks 12 and 16. We detected serum concentrations of the sex hormones estradiol (E2), follicle‐stimulating hormone (FSH), and anti‐Müllerian hormone (AMH), using enzyme‐linked immunosorbent assays. Hematoxylin and eosin staining showed ovarian tissue structure and enabled the counting of follicles. Hepatocyte growth factor (HGF) and insulin‐like growth factor 1 (IGF‐1) expression in ovarian tissue was observed by immunohistochemistry. Results Ovarian function in lupus mice was abnormal, as indicated by decreased serum E2 and AMH concentrations, and increased FSH concentrations. HUC‐MSC transplantation caused significant upregulation of serum E2 and AMH and downregulation of FSH (all p

Objectives Chronic kidney disease (CKD) is a long-term condition characterized by poor prognosis and a high mortality rate. Panax notoginseng saponins (PNS) are the main active ingredient of the traditional Chinese herb Panaxnotoginseng(Burk.)F.H.Chen, which has been widely reported to have various pharmacological effects. Here, we examined the effect of PNS on renal function and the modulation of intestinal flora and intestinal barrier in a rat model of adenine-induced CKD.Methods Adenine was used to establish a rat model of CKD, biochemical testing, histopathologic examination, ELISA, immunohistochemical assay, western blot assay, and fecal microbiota 16s rRNA analysis was used to test the effect of PNS on CKD rats.Results Adenine induced a significant decrease in glomerular filtration rate, an increase in urinary protein excretion rate, and pathological damage to renal tissue in CKD rats. TNF-α, MCP-1, IL-1β, IL-18, TMAO, and endotoxin levels were increased in the blood of the model rats. Application of PNS countered the effects of adenine, restoring the above parameters to the level observed in healthy rats. In addition, activation of the inflammatory proteins NF-κB (p65) and NLRP3 and the fibrosis-associated proteins α-SMA and smad3 were inhibited in the kidneys of CKD rats. Furthermore, PNS promoted the expression of the tight junction proteins Occludin and ZO-1, increased SIgA levels, strengthened intestinal immunity, reduced mechanical damage to the intestine, was reduced levels of DAO and D-LA. Our data suggest PNS may delay CKD by restoring gut microbiota, and through the subsequent generation of a microbial barrier and modulation of microbiota metabolites.Conclusions In conclusion, PNS may inhibit the development of inflammation and fibrosis in the kidney tissue through regulation of intestinal microorganisms and inhibition of the activation of pro-inflammatory and pro-fibrotic proteins in the kidney.

Background The number of neutrophils is significantly reduced in myelodysplastic syndrome (MDS), but the molecular basis remains unclear. We recently found that miR-34a was significantly increased in MDS neutrophils. Therefore, this study aims to clarify the effects of aberrant miR-34a expression on neutrophil counts.Methods miR-34a mimics/inhibitor transfection were performed in neutrophil-like differentiated HL60 (dHL60) cells, and a FACSCalibur flow cytometer was used to measure ROS production and apoptosis. In addition, the Cdc42-WASP-Arp2/3 pathway inhibitor (ML141) and activator (CN02) treated the dHL60 cells, and then ROS production, apoptosis and related proteins expression were detected. And, luciferase reporter assay to verify the relationship of miR-34a and the Cdc42-WASP-Arp2/3 pathway.Results overexpression of miR-34a could induce ROS production and apoptosis, decrease the expression levels of DOCK8, p-WASP, WASP, Arp2, Arp3, and increase F-actin’s expression. Meanwhile, knockdown of miR-34a could decrease ROS production and apoptosis, increase the expression of DOCK8, p-WASP, WASP, Arp2, Arp3, and decrease F-actin’s expression. Immunofluorescence staining showed aberrant miR-34a and Cdc42-WASP-Arp2/3 pathway could induce F-actin membrane transfer. Luciferase reporter assay indicated that DOCK8 was a direct target gene of miR-34a.Conclusion These data indicates miR-34a may induce neutrophil apoptosis by regulating Cdc42-WASP-Arp2/3 pathway-mediated F-actin remodeling and ROS production.

To investigate the effect of different thawing methods on the quality of frozen cuttlefish, six different thawing methods were used: hydrostatic thawing (HT), flowing water thawing (FWT), saline solution thawing (SWT), ultrasonic water thawing (UWT), microwave thawing (MT), and 4°C refrigerator thawing (RT). In this study, the water retention (thawing loss rate, centrifugal loss rate, and cooking loss), pH value, malondialdehyde content, TVB-N value, and sulfhydryl content were measured to evaluate the quality after thawing. Protein secondary structure was measured using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, protein tertiary structure was obtained by fluorescence spectroscopy and water migration was determined using low-field NMR spectroscopy. The results showed that the microwave thawing time was the shortest, but the water holding capacity after thawing was the worst, and the TVB-N content was the highest at 14.31 mg/100 g. Ultrasonic thawing led to the best water holding capacity, but ultrasound promoted the oxidation of protein and fat. Microscopic observation showed that the muscle fiber bundles in the saline solution thawing samples were compactly arranged and intact, with minimal gaps. The samples thawed in saline solution had the highest hardness and chewiness. The results of comprehensive analysis showed that saline solution thawing and ultrasonic water thawing are more suitable for thawing cuttlefish, and this study provides some theoretical basis for the selection of thawing methods in the actual production of cuttlefish.

Bananas (Musa spp.) enriched in resistant starch displayed multiple health benefits for diabetes. Here, we showed that banana starch administered to diabetic rats improved animal depressive-like behaviours of mood disorders. Four weeks of banana starch diet to high-sugar, high-fat, and STZ-induced diabetic rats lowered their blood insulin resistance, but increased their plasma HDL cholesterol and 5-HT levels, compared to the control groups of rats. The banana starch diet reconstructed the gut microbiota and increased their metabolite of butyrate, as well as increased the activity of superoxidase in diabetic rats. Furthermore, Banana starch intervention significantly increased the exhaustion time of the diabetic rats, and almost restored it to the normal state of control groups in their swimming and tail suspension tests. Together, our results indicated the modulation of the gut-microbiota-brain axis as a possible mechanism that enables the banana starch diet as a potential therapeutic way for diabetes-associated mood disorders.