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Abstract Background Wheat is one of major sources of human cadmium (Cd) intake. Reducing the grain Cd concentrations in wheat is urgently required to ensure food security and human health. In this study, we performed a field experiment at Wenjiang experimental field of Sichuan Agricultural University (Chengdu, China) to reveal the effects of FeCl3 and Fe2(SO4)3 on reducing grain Cd concentrations in dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB). Results Soil application of FeCl3 and Fe2(SO4)3 (0.04 M Fe3+/m2) significantly reduced grain Cd concentration in DPW at maturity by 19.04% and 33.33%, respectively. They did not reduce Cd uptake or root-to-shoot Cd translocation, but increased Cd distribution in lower leaves, lower internodes, and glumes. Meanwhile, application of FeCl3 and Fe2(SO4)3 up-regulated the expression of TpNRAMP5, TpNRAMP2 and TpYSL15 in roots, and TpYSL15 and TpZIP3 in shoots; they also downregulated the expression of TpZIP1 and TpZIP3 in roots, and TpIRT1 and TpNRAMP5 in shoots. Conclusions The reduction in grain Cd concentration caused by application of FeCl3 and Fe2(SO4)3 was resulted from changes in shoot Cd distribution via regulating the expression of some metal transporter genes. Overall, this study reports the physiological pathways of soil applied Fe fertilizer on grain Cd concentration in wheat, suggests a strategy for reducing grain Cd concentration by altering shoot Cd distribution.

In this study, advanced oxidation-protective CrSi coatings were developed and deposited on N-type (Zr,Ti)Ni(Sn,Sb) and P-type (Zr,Ti)Co(Sn,Sb) thermoelectric (TE) materials using an environmentally friendly closed field unbalanced magnetron sputtering PVD system. The oxidation behaviour of the CrSi-coated and uncoated samples was evaluated through static oxidation tests at 500 °C and 600 °C for 10h and 50 h, respectively. In addition, the samples were exposed to cyclic oxidation tests between 25 °C and 500 °C for 10, 30 and 50 cycles, with each cycle consisting of 1h of oxidation at 500 °C, to examine the coating ability to withstand thermal shock, which is involved in the service of TE devices. The surface morphology, cross-section layer structure, elemental distribution and phase constitution were analysed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDX) and X-ray diffraction (XRD). The mass gain after the oxidation tests was measured and calculated for each sample to study the oxidation kinetics. The uncoated samples exhibited a considerable amount of oxidation, leading to change in the surface morphologies, and the formation of alternated layers including oxide products (Zr(Ti)O2, SnO2) and Ni3Sn4 compound for the N-type and (Zr(Ti)O2, SnO2, Sb2O4) and CoSb compound for the P-type material, after static and cyclic oxidation tests. The experimental work in this study has, for the first time, demonstrated that the CrSi coatings developed with very high thermal stability and oxidation resistance can effectively protect both the N-type and P-type materials from oxidation and sublimation even during cyclic oxidation tests. The strong affinity of Cr and Si to oxygen can trap oxygen, retard its inward diffusion and thus protect the TE material substrate from oxidation. This finding could pave the way towards the further development of long-life high-performance TE generators and devices, thus contributing to the net zero target.

Abstract The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.

Abstract This study aimed to reveal the diversity and variation in panicle traits of the Chinese prickly ash and clarify their influence on the its systematic classification to provide a theoretical basis and technical support for the efficient utilization of Chinese prickly ash germplasm resources and breeding. Sixteen panicle traits were identified from 35 Chinese prickly ash germplasm resources from 2021 to 2022. The diversity of these panicle traits and their role in the plant’s systematic classification were studied using variance, correlation, cluster, and principal component analyses. Cluster analysis showed that the 35 Chinese prickly ash germplasm resources could be divided into two groups with Euclidean distances of 25. Further analysis showed that yield traits such as panicle length, panicle width, primary branching, grain number per panicle, and grain weight per panicle were significantly positively correlated with grain chlorophyll content, while grain anthocyanin content was negatively correlated with both panicle (panicle length, panicle width, panicle length to width ratio, primary branching, grain number per panicle, and grain weight per panicle) and grain characteristics (single grain weight, thousand-grain weight, grain length, grain width and fruit shape index). In conclusion, Chinese prickly ash germplasms have diverse panicle traits. Z. armatum has dark green grains, long and wide panicles, a long conical shape, many primary branches, high grain weight, and high grain number per panicle. In contrast, Z. bungeanum has bright red seeds, a panicle width larger than its length, short and conical panicles, a small number of primary branches, and low grain weight per panicle and number of grains per panicle. Overall, Z. armatum had a significant yield advantage over Z. bungeanum.

Abstract Brucellosis is a difficult to treat infection that requires antibiotic combinations administered over several weeks for clearance of infection and relapse prevention. This systematic review summarizes current evidence for antibiotic treatment of human brucellosis. PubMed, EMBASE, Scopus, CINAHL, Web of Science, and China Academic Journal databases were searched for prospective studies that had compared different antibiotic regimens for treating human brucellosis in the last 25 years. Thirty-four studies recruiting 4182 participants were eligible. Standard dual therapy with doxycycline + rifampicin had a higher risk of treatment failure compared to triple therapy which added streptomycin (RR: 1.98, 95% CI 1.17–3.35, p = 0.01) or levofloxacin (RR: 2.98, 95% CI 1.67–5.32, p = 0.0002), but a similar or lower risk compared to alternative dual antibiotic combinations (p > 0.05). The same combination had a higher risk of relapses compared to triple therapy which added streptomycin (RR: 22.12, 95% CI 3.48–140.52, p = 0.001), or levofloxacin (RR: 4.61, 95% CI 2.20–9.66, p 0.05). Triple antibiotic therapy is more effective than standard dual therapy with rifampicin and doxycycline. However, the latter is also efficacious and suitable for uncomplicated disease.

Abstract The microRNAs (miRNAs) of their hosts play an important role in regulating both the innate and adaptive immune responses to Cryptosporidium parvum infection. The mechanisms of autophagy and apoptosis are important components of the defense system against C. parvum infection. In this study, we investigate the role of miRNA-199a-3p in regulating MTOR-mediated autophagy and apoptosis in HCT-8 cells induced by C. parvum. The expression of miR-199a-3p increased at 3, 6 and 12 hours postinfection (hpi) but decreased at 24 and 48 hpi. The upregulation of miR-199a-3p promoted autophagy and apoptosis and limited the parasite burden in HCT-8 cells after C. parvum infection. The downregulation of miR-199a-3p inhibited the autophagy and apoptosis induced by C. parvum and enhanced the parasite burden in HCT-8 cells. A luciferase reporter showed that MTOR was a target gene of miR-199a-3p. Suppressed expression of MTOR by small interfering RNA (siRNA) promoted autophagy and apoptosis and limited C. parvum burden in HCT-8 cells. Co-transfection with miR-199a-3p inhibitor or si-mTOR revealed that miR-199a-3p regulates autophagy and apoptosis in HCT-8 cells through MTOR, to resist C. parvum infection. In conclusion, intestinal epithelial cells defend against C. parvum infection by regulating their autophagy and apoptosis through the miR-199a-3p-MTOR axis.

Abstract The association between composite dietary antioxidant index (CDAI) and asthma remains unclear. Our study aimed to investigate the association of CDAI with asthma in children aged 3–18 years in the United States. Cross-sectional analyses were carried out on 18,118 children aged 3–18 years old. Data was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2020. The Composite Dietary Antioxidant Index (CDAI) was measured by assessing the consumption of six dietary antioxidants (vitamin A, vitamin C, vitamin E, zinc, selenium and carotenoids). The association between CDAI and asthma was explored using multivariate weighted logistic regression, subgroup analyses, and sensitivity analyses. Among the 18,118 participants, 2045 (11.3%) reported a diagnosis of asthma by a healthcare provider. In both the crude and adjusted models, the odds ratios (ORs) for asthma with CDAI were not significant. Specifically, in the fully adjusted model, the OR for T2 was 0.98 (95% CI 0.83, 1.17) and the OR for T3 was 1.00 (95% CI 0.76, 1.31). Subgroup analyses by sex, age and BMI category also showed no significant associations. Sensitivity analyses, including weighted logistic multivariate analyses adjusting for family history of asthma, confirmed the absence of a significant association between CDAI and asthma. Our study showed no significant association between CDAI and asthma in children and adolescents.

Abstract Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (−44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.

Abstract Despite widespread agreement in the scholarly community about the significance of academic title structure on research output, research on the underlying mechanisms remains insufficient. Social contribution and research resources were selected as mediating variables, panel data of the materials science and engineering discipline of 30 Chinese universities from 2016 to 2020 were chosen as the research samples, and a fixed-effects model was subsequently applied to conduct a chain mediating effect test. The results showed: (1) Both the proportion of national-level talents and that of senior titles can promote research output, with the former having a much greater effect, while the proportion of associate senior titles has an indistinctive negative correlation with research output. (2) Both the proportion of national-level talents and that of senior titles can significantly enhance research output through the chain mediating effect of social contribution and research resources, with national-level talents having a stronger ability to make social contributions and obtain research resources. (3) Social contribution is more effective than research resources in enhancing research output. Based on the findings, it is recommended to improve policies for introducing high-end talents and to increase support for researchers with associate senior titles. Furthermore, it is advisable to establish a research evaluation system based on social influence, guiding researchers to obtain research resources and enhance research output through social contributions.

Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.

Hexavalent chromium (Cr(VI)) has been identified as a Class I human carcinogen, but its carcinogenic mechanism is currently unclear. There is still a lack of understanding of its associations with early pulmonary inflammatory damages. Inflammation is an important stage before the occurrence of tumors, and under the long-term stimulation of inflammation, it can promote the development of tumors. In this study, the aim is to explore the effect of Cr(VI) exposure on pulmonary inflammation and its relationship with the mechanism of inflammation cancer transformation. We established a Cr(VI) exposure model in SD rats using tracheal instillation of potassium dichromate solution, and collected samples at the time of cessation of exposure and 14 days after cessation of exposure. Analyzing the experimental results, it was found that the lung index increased after exposure to Cr(VI), promoting the occurrence of apoptosis in lung tissue cells and exacerbating lung tissue damage. The damage situation improved after exposure termination; Inductively coupled plasma mass (ICPRQ) spectrometer detection found that the exposed group had significantly increased levels of blood chromium, blood manganese, blood copper, blood arsenic, urine chromium, urine copper, and urine lead; After two weeks of repair, blood chromium and blood manganese levels were significantly lower than those in the same dose group of the exposure group, while blood copper levels were significantly higher than those in the same dose group of the exposure group. There was no significant difference in blood arsenic levels between the exposure group and the exposure group. Urine chromium and urine lead levels were significantly lower than those in the same dose group of the exposure group, while urine copper levels only increased. At the same time, it was found that Cr(VI) exposure caused disruption of oxidative stress levels in rat lung tissues. After 14-day exposure, Cr(VI) significantly decreased and oxidative stress levels significantly decreased. Further investigation revealed that Cr(VI) induces activation of inflammasomes NLRP3, AIM2, and their signaling pathways in lung inflammatory injuries, but this condition persists even after cessation of exposure. The study suggested that in hexavalent chromium induced lung tissue injuries in rats, NLRP3 and AIM2 inflammasomes and their signaling pathways activation. Furthermore, the characteristic of sustained activation after cessation of exposure was also indicated. These results provide new ideas and references for further elucidating the mechanisms of Cr(VI), lung inflammation and inflammation cancer transformation.

Objective: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. Methods: Robust rank aggregation (RRA) method was used to integrate NAFLD-related gene expression datasets. For fatty liver study, adeno-associated virus (AAV) delivery and genetic knockout mice were used to create IGFBP2 (Insulin-like growth factor binding protein 2) gain- or loss-of function models. Western blot, Co-immunoprecipitation (Co-IP), immunofluorescent (IF) staining, luciferase assay, molecular docking simulation were performed to reveal the IGFBP2-EGFR-STAT3 axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. Results: By using RRA method, the present study identified IGFBP2 being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. Conclusions: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

In recent years, artificial intelligence (AI), especially deep learning models, has increasingly been integrated into diagnosing and treating diabetic retinopathy (DR). From delving into the singular realm of ocular fundus photography to the gradual development of proteomics and other molecular approaches, from machine learning (ML) to deep learning (DL), the journey has seen a transition from a binary diagnosis of “presence or absence” to the capability of discerning the progression and severity of DR based on images from various stages of the disease course. Since the FDA approval of IDx-DR in 2018, a plethora of AI models has mushroomed, gradually gaining recognition through a myriad of clinical trials and validations. AI has greatly improved early DR detection, and we’re nearing the use of AI in telemedicine to tackle medical resource shortages and health inequities in various areas. This comprehensive review meticulously analyzes the literature and clinical trials of recent years, highlighting key AI models for DR diagnosis and treatment, including their theoretical bases, features, applicability, and addressing current challenges like bias, transparency, and ethics. It also presents a prospective outlook on the future development in this domain.

BackgroundOlder patients with advanced cholangiocarcinoma lack systemic therapy standards. These people have a high risk of chemotherapy, accompanied by adverse reactions and even discontinuation of treatment.Case presentationWe report a 78-year-old female subject with advanced intrahepatic cholangiocarcinoma presenting with unresectable lesions involving the hepatic veins, along with extensive metastatic lymph nodes. After the geriatric assessment, capecitabine was utilized for only one cycle owing to adverse events (AEs). Next, a combination of low-dose lenvatinib and tislelizumab was administrated as a second-line treatment, which resulted in remarkable early tumor shrinkage. The following individual lenvatinib taper enabled a manageable safety profile and durable deep response. A near-complete response was achieved, with the primary tumor significantly reducing from 5.6 cm × 4.7 cm to nearly complete disappearance, accompanied by complete regression of lymph nodes, and both progression-free survival and overall survival exceeding 24 months.ConclusionThe case provides valuable insights that could influence future treatment strategies for older patients with advanced cholangiocarcinoma who are unsuitable for chemotherapy. The dose-individualized chemotherapy-free regime of lenvatinib and tislelizumab might be used in similar cases to improve their outcomes.

IntroductionThe identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis.MethodsPatient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model.ResultsUnivariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction.DiscussionThe novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

In Northeast China, permafrost is controlled by a combination of biotic, climatic, physiographic, and anthropogenic factors. Due to the complexity of these governing or influencing factors, it is challenging to exactly describe the features of the Xing’an permafrost in Northeast China. By integrating remote sensing (RS) and geographic information system (GIS) technologies, we have quantified these influencing factors of permafrost changes as an important approach to understanding the nature of latitudinal and mountain permafrost in Northeast China at the mid-latitudes in the Northern Hemisphere. In this study, we combine Geographical Detector (Geodetector) model, trend analysis, and multi-source RS data to quantify the controlling or influencing factors of permafrost thermal state and of permafrost changes, and explain the interactions among permafrost, environment, and climate. The results indicate that, at the regional scale, changes in the thermal state of permafrost are primarily governed or influenced by mean annual land surface temperature (MALST), precipitation, and snow cover duration (SCD). Topographic factors also affect the spatial patterns of permafrost development. Additionally, in the context of climate warming, the insulation effect of snow cover on the permafrost is weakened, or has been weakening. Moreover, the interactive effects among various factors significantly enhance their explanatory power for changes in the thermal state of permafrost. The study emphasizes the complexity of the interactions among permafrost, climate, and the environment, and highlights the significance of understanding these interactions for regional socio-economic development, ecological management, carbon pool stabilization, and research on future climate change in Northeast China.

In this study, the fabricated Hf-free N-type (Zr,Ti)Ni(Sn,Sb) and P-type (Zr,Ti)Co(Sn,Sb) thermoelectric materials were subjected to cyclic oxidation testing at 500 °C for 10, 30, and 50 cycles. The oxidation behaviour of the materials was systematically investigated by evaluating mass gain to study the oxidation kinetics and by analysing surface morphology, phase constitution and elemental distribution to investigate the oxidation mechanism. The results indicated that both of the materials were severely oxidised during the cyclic oxidation testing, and the mass gain followed the parabolic kinetics and the parabolic rate constant (kp) being 0.006165 mg2cm−4s−1 and 0.000109 mg2cm−4s−1 for the N-type and the P-type TE materials, respectively. Alternated multilayers of Ni3Sn4+SnO2+(Zr,Ti)O2 and CoSb + SnO2+Sb2O4+(Zr,Ti)O2 were identified on the surface of the N-type and P-type materials, respectively, after the cyclic testing, which would deteriorate the thermoelectric performance of the materials. The outcome of this study strongly suggests that it is essential to improve the oxidation resistance and the thermal stability of the N-type (Zr,Ti)Ni(Sn,Sb) and P-type (Zr,Ti)Co(Sn,Sb) thermoelectric materials for high-temperature applications.

Abstract This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion’s analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Abstract Background Cryptosporidium parvum is an apicomplexan zoonotic parasite causing the diarrheal illness cryptosporidiosis in humans and animals. To invade the host intestinal epithelial cells, parasitic proteins expressed on the surface of sporozoites interact with host cells to facilitate the formation of parasitophorous vacuole for the parasite to reside and develop. The gp40 of C. parvum, named Cpgp40 and located on the surface of sporozoites, was proven to participate in the process of host cell invasion. Methods We utilized the purified Cpgp40 as a bait to obtain host cell proteins interacting with Cpgp40 through the glutathione S-transferase (GST) pull-down method. In vitro analysis, through bimolecular fluorescence complementation assay (BiFC) and coimmunoprecipitation (Co-IP), confirmed the solid interaction between Cpgp40 and ENO1. In addition, by using protein mutation and parasite infection rate analysis, it was demonstrated that ENO1 plays an important role in the C. parvum invasion of HCT-8 cells. Results To illustrate the functional activity of Cpgp40 interacting with host cells, we identified the alpha-enolase protein (ENO1) from HCT-8 cells, which showed direct interaction with Cpgp40. The mRNA level of ENO1 gene was significantly decreased at 3 and 24 h after C. parvum infection. Antibodies and siRNA specific to ENO1 showed the ability to neutralize C. parvum infection in vitro, which indicated the participation of ENO1 during the parasite invasion of HCT-8 cells. In addition, we further demonstrated that ENO1 protein was involved in the regulation of cytoplasmic matrix of HCT-8 cells during C. parvum invasion. Functional study of the protein mutation illustrated that ENO1 was also required for the endogenous development of C. parvum. Conclusions In this study, we utilized the purified Cpgp40 as a bait to obtain host cell proteins ENO1 interacting with Cpgp40. Functional studies illustrated that the host cell protein ENO1 was involved in the regulation of tight junction and adherent junction proteins during C. parvum invasion and was required for endogenous development of C. parvum. Graphical Abstract

In recent years, the utilisation of oxygen-deficient zirconia (ZrO2-α), commonly referred to as black zirconia, has garnered considerable attention due to its potential applications for solid oxide fuel cells (SOFCs), gas sensors, biomedical implant materials, and photocatalysis. However, current methods employed to manufacture ZrO2-α exhibit noticeable limitations regarding their scalability, environmental sustainability, and cost-effectiveness. Our recent work has successfully demonstrated the feasibility for bulk conversion of conventional white zirconia into oxygen-deficient black zirconia through direct current (DC) plasma treatment (i.e. plasma blackening). This study elucidates the conditions for plasma blackening and provides a unique mechanism for the bulk transformation of zirconia. A systematic investigation of different plasma technologies (DC, active-screen plasma), treatment configurations (contact conditions, cathode material, and cathode potential), and treatment parameters (voltage, temperature, duration) uncover the crucial variables that influence the feasibility and rate of the reduction process. The reduction of zirconia is shown to initiate from localised contacting points at the cathode-facing surface and grow, with a hemispherical shape, towards the anode-facing surface. A series of development stages are proposed for the process, namely: bulk oxygen vacancy conductance, surface activation, oxygen vacancy generation and a moving cathode front. The findings of this study provide insights into the underlying mechanisms involved in the bulk-reduction of zirconia and help to pave the way towards future scalable and cost-effective generation of oxygen-deficient zirconia.

Using recycled concrete fines (RFs) as a supplementary cementitious material in blended cement systems offers potential benefits for the construction industry. This study investigated the mechanical properties, hydration development, and microstructural evolutions of blended Portland cement systems incorporating different particle-size distributions of untreated RFs. The results highlighted that finer RFs improved the compressive strength of mortar and influenced hydration by promoting monocarbonate formation. The incorporation of RFs optimizes the pore structure in the early stage but increases porosity. RFs affected the distribution of capillary pores and created a rougher and more complex surface compared to inert mineral admixtures. Furthermore, the particle size of RFs impacted the fractal dimension of multi-scale pore sizes.

Chapter 2 of the Vegetable Production Handbook of Florida

Chapter 5 of the Vegetable Production Handbook of Florida

BackgroundChronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease. ObjectiveThis study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors. MethodsBaseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes. ResultsA national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR 5.18 μmol/L, LDL cholesterol >3.37 μmol/L, BMI ≥30 kg/m2, and hypertension. ConclusionsIn a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified. Trial RegistrationClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471

ABSTRACT Purpose: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. Methods: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. Results: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. Conclusions: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.

Hexavalent chromium (Cr(VI)) is a hazardous metallic compound commonly used in industrial processes. The liver, responsible for metabolism and detoxification, is the main target organ of Cr(VI). Toxicity experiments were performed to investigate the impacts of low-dose exposure to Cr(VI) on rat livers. It was revealed that exposure of 0.05 mg/kg potassium dichromate (K2Cr2O7) and 0.25 mg/kg K2Cr2O7 notably increased malondialdehyde (MDA) levels and the expressions of P-AMPK, P-ULK, PINK1, P-Parkin, and LC3II/LC3I, and significantly reduced SOD activity and P-mTOR and P62 expression levels in liver. Electron microscopy showed that CR(VI) exposure significantly increased mitophagy and the destruction of mitochondrial structure. This study simulates the respiratory exposure mode of CR(VI) workers through intratracheal instillation of CR(VI) in rats. It confirms that autophagy in hepatocytes is induced by low concentrations of CR(VI) and suggest that the liver damage caused by CR(VI) may be associated with the AMPK-related PINK/Parkin signaling pathway.

We demonstrate the generation of correlated photon pairs by using a hybrid integrated quantum photonic platform, where the dual-layer platform consists of a high-index doped silica glass (HDSG) layer to accommodate low-loss linear components and an SiN-based layer to accommodate the photon source. Leveraging the low-loss fiber coupling to the HDSG waveguide and the high nonlinearity of the SiN waveguide, we experimentally realize integrated source of photon pairs with high heralding efficiency. The directly measured photon pair rate is up to 87 KHz (corresponding to 1.74 × 10−3 pairs per pulse) when the coincidence-to-accidental ratio is greater than 10. The raw heralding efficiency can reach 18%. If the filtering loss is excluded, the heralding efficiency can further reach 29%.

Edamame (Glycine max (L.) Merr.), a specialty soybean prized for its nutritional value and taste, has witnessed a surge in demand within the U.S. However, subpar seedling stands have hindered its production potential, necessitating increased inputs for farmers. This study aims to uncover potential physiological factors contributing to low seedling emergence in edamame. We conducted comprehensive assessments on thirteen prominent edamame genotypes alongside two food-grade and two grain-type soybean genotypes, focusing on germination and emergence speed in both laboratory and field settings. Additionally, we employed single electrical conductivity tests and identified and quantified seed leachate components to distinguish among soybean types. Furthermore, using a LabField™ simulation table, we examined seed emergence across a wide soil temperature range (5°C to 45°C) for edamame and other soybean types. All seeds were produced under the same environmental conditions, harvested in Fall 2020, and stored under uniform conditions to minimize quality variations. Our findings revealed minimal divergence in emergence percentages among the seventeen genotypes, with over 95% germination and emergence in laboratory conditions and over 70% emergence in the field. Nonetheless, edamame genotypes typically exhibited slower germination speeds and higher leachate exudates containing higher soluble sugars and amino acids. Seed size did not significantly impact total emergence but was negatively correlated with germination and emergence speed, although this effect could be mitigated under complex field conditions. Furthermore, this study proposed differences that distinguish edamame from other soybean types regarding ideal and base temperatures, as well as thermal time. The finds offer valuable insights into edamame establishment, potentially paving the way for supporting local edamame production in the U.S.

In this study, an iris recognition technique based on enhanced EnhanceDeepIris model is proposed in order to examine iris recognition at a deeper level. The process first uses convolutional features to extract human iris features. Then, in order to solve the deformation problem caused by the radial data of iris texture, the sequential metric model is introduced to realize the effective recognition of iris. Finally, the structure of the model is thoroughly examined to investigate its actual performance. The study found that after running the four algorithms on the ND-IRIS-0405 and CASIA-Lamp datasets, the loss function value of the research method began to approach its lowest value at the 14th and 9th iterations, while the other algorithms continued to slowly decrease. Additionally, at the 5th and 4th iterations respectively, the accuracy of the research method was nearly 91.00%.After 20 classification predictions, the average recognition accuracies of the research method proposed in this paper, iris segmentation method based on end-to-end multi-task segmentation network IrisST-Net, iris recognition method based on full complex-valued neural network, and iris recognition method with hybrid preprocessing and feature extraction were 99.88%, 98.72%, 97.47%, and 89.77%, respectively. These findings suggest that the study approach recognizes the iris the best and can identify its primary contour information with accuracy. The results of the application demonstrate that the research method provides the clearest detection of the iris edge, with less noise, and can accurately detect the main contour information of the iris. This provides a reference for optimizing related technologies in the field of image recognition.

The atmospheric infrared ultraspectral sounder (AIUS) is China's first infrared occultation spectrometer onboard the GaoFen-5 satellite. This instrument provides measurements in the near-infrared and mid-infrared spectral regions with a spectral resolution of 0.02 cm$^{-1}$, monitoring key greenhouse gases like methane (CH$_{4}$). In this study, we have developed a physics-based retrieval algorithm for accurately deriving CH$_{4}$ mole fraction profiles from infrared absorption spectra. The retrieval algorithm is applied to the AIUS and successfully obtains CH$_{4}$ mole fraction profiles from January to December 2019 over Antarctic. The validation results show that the retrieval algorithm has a satisfactory performance using AIUS measurements, with average relative standard deviation of the differences less than 7.2% throughout the altitude range of 10–70 km.

The mission of blind image quality evaluation is currently a challenging computer vision problem. Due to the shortage of reference images, it is hard for blind image quality evaluation methods to achieve the same performance as full reference image quality evaluation methods. In addition, current quality evaluation methods are difficult to effectively forecast the quality scores of synthesized distorted images as well as real distorted images. To address such issues, this study proposed a cyclic generative adversarial network composed of a quality perception network and a quality regression network on the grounds of generative adversarial networks. For further enhancing the predictive performance of quality aware networks, this study proposed using attention blocks for adaptively fusing high-level semantic features and low-level semantic features. It extracted content and distortion information from images through an image quality evaluation method on the grounds of content perception and distortion inference. And according to the different properties of the extracted features, adaptive fusion blocks were used for adaptively fusing content features and distortion features. Experiments showcased that the Spearman order correlation coefficient and Pearson linear correlation coefficient obtained by the proposed method on multiple datasets were higher than other similar methods. At the same time, the proposed method has achieved good prediction results on various types of distorted images, and has surpassed other methods. The prediction accuracy of the proposed method on five types of distortion was 0.971, 0.963, 0.984, 0.971, and 0.926, respectively. The proposed method achieved the highest predictive accuracy on all distortion types in the LIVE dataset, with predicted accuracy values of 0.973, 0.965, 0.984, 0.963, and 0.944, respectively. In summary, the proposed method not only achieved good prediction accuracy, but also had strong generalization performance in cross dataset testing. This provides a scientific and effective research direction for blind image quality evaluation.

Accurate satellite precipitation estimates are vital for understanding global and large-scale regional water cycles. Among the many factors influencing satellite precipitation data quality, the detection and accuracy of precipitation products at different atmospheric aerosol concentrations are not well studied. In this study, we investigated the impact of atmospheric aerosols on the accuracy of satellite precipitation products (IMERG) over North China by comparing performance metrics such as bias, normalized root mean squared error, probability of detection (POD), and false alarm ratio (FAR) under different atmospheric aerosol conditions. The results revealed that IMERG generally exhibits poorer detectability and quantification under pollution condition. Based on the error decomposition, the estimated errors in autumn and winter were dominated by false biases, which are mainly affected by atmospheric aerosols. At the sensor level, the FARs of both infrared (IR) and passive microwave sensors show escalating trends as pollutant concentrations increase. The POD of IR sensors is affected by pollution. Pollution has a significant impact on IR detection capability. Our findings suggest that atmospheric aerosols may impact the accuracy of IMERG precipitation estimates over Northern China and need to be taken into consideration in the IMERG retrieval process and data utilization.

Abstract Background Intracellular DNA-sensing pathway cGAS-STING, inflammasomes and pyroptosis act as critical natural immune signaling axes for microbial infection, chronic inflammation, cancer progression and organ degeneration, but the mechanism and regulation of the crosstalk network remain unclear. Main body of the abstract Cellular stress disrupts mitochondrial homeostasis, facilitates the opening of mitochondrial permeability transition pore and the leakage of mitochondrial DNA to cell membrane, triggers inflammatory responses by activating cGAS-STING signaling, and subsequently induces inflammasomes activation and the onset of pyroptosis. Meanwhile, the inflammasome-associated protein caspase-1, Gasdermin D, the CARD domain of ASC and the potassium channel are involved in regulating cGAS-STING pathway. Importantly, this crosstalk network has a cascade amplification effect that exacerbates the immuno-inflammatory response, worsening the pathological process of inflammatory and autoimmune diseases. Given the importance of this crosstalk network of cGAS-STING, inflammasomes and pyroptosis in the regulation of innate immunity, it is emerging as a new avenue to explore the mechanisms of multiple disease pathogenesis. Therefore, efforts to define strategies to selectively modulate cGAS-STING, inflammasomes and pyroptosis in different disease settings have been or are ongoing. In this review, we will describe how this mechanistic understanding is driving possible therapeutics targeting this crosstalk network, focusing on the interacting or regulatory proteins, pathways, and a regulatory mitochondrial hub between cGAS-STING, inflammasomes, and pyroptosis. Short conclusion This review aims to provide insight into the critical roles and regulatory mechanisms of the crosstalk network of cGAS-STING, inflammasomes and pyroptosis, and to highlight some promising directions for future research and intervention.

The clam Cyclina sinensis is an economically important marine species in China. However, overfishing, habitat destruction, and inbreeding have led to the destruction of genetic resources. In this study, five natural populations [Dandong (DD), Dongying (DY), Tianjin (TJ), Wenzhou (WZ), and Yancheng (YC)] from different geographical locations were relocated and cultured homogeneously to study their potential for translocation and environmental adaptation by observing growth performance and nutrient content. There were significant differences in the growth rates of shell length (SL), shell height (SH), and shell width (SW) among the five populations (P

Objective: Diabetic retinopathy is one of the major complications of diabetes. In this study, a diabetic retinopathy risk prediction model integrating machine learning models and SHAP was established to increase the accuracy of risk prediction for diabetic retinopathy, explain the rationality of the findings from model prediction and improve the reliability of prediction results. Methods: Data were preprocessed for missing values and outliers, features selected through information gain, a diabetic retinopathy risk prediction model established using the CatBoost and the outputs of the mode interpreted using the SHAP model. Results: One thousand early warning data of diabetes complications derived from diabetes complication early warning dataset from the National Clinical Medical Sciences Data Center were used in this study. The CatBoost-based model for diabetic retinopathy prediction performed the best in the comparative model test. ALB_CR, HbA1c, UPR_24, NEPHROPATHY and SCR were positively correlated with diabetic retinopathy, while CP, HB, ALB, DBILI and CRP were negatively correlated with diabetic retinopathy. The relationships between HEIGHT, WEIGHT and ESR characteristics and diabetic retinopathy were not significant. Conclusion: The risk factors for diabetic retinopathy include poor renal function, elevated blood glucose level, liver disease, hematonosis and dysarteriotony, among others. Diabetic retinopathy can be prevented by monitoring and effectively controlling relevant indices. In this study, the influence relationships between the features were also analyzed to further explore the potential factors of diabetic retinopathy, which can provide new methods and new ideas for the early prevention and clinical diagnosis of subsequent diabetic retinopathy.

Abstract Background Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. Methods RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. Results The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. Conclusion We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

Abstract Background With the promotion of “One Health,” the health of animals and their impact on the environment have become major concerns recently. Widely distributed in China, the whooper swans (Cygnus cygnus) and black swans (Cygnus atratus) are not only important to the ecological environment, but they may also potentially influence public health security. The metagenomic approach was adopted to uncover the impacts of the gut microbiota of swans on host and public health. Results In this study, the intestinal microbiome and resistome of migratory whooper swans and captive-bred black swans were identified. The results revealed similar gut microbes and functional compositions in whooper and black swans. Interestingly, different bacteria and probiotics were enriched by overwintering whooper swans. We also found that Acinetobacter and Escherichia were significantly enriched in early wintering period swans and that clinically important pathogens were more abundant in black swans. Whooper swans and black swans are potential reservoirs of antibiotic resistance genes (ARGs) and novel ARGs, and the abundance of novel ARGs in whooper swans was significantly higher than that in black swans. Metagenomic assembly–based host tracking revealed that most ARG-carrying contigs originated from Proteobacteria (mainly Gammaproteobacteria). Conclusions The results revealed spatiotemporal changes in microbiome and resistome in swans, providing a reference for safeguarding public health security and preventing animal epidemics.

Abstract Aerobic glycolysis, a typical phenotype in human tumors, is associated with tumor progression and chemotherapy resistance. The present study demonstrated that cisplatin-resistant oral squamous cell carcinoma (OSCC) cells exerted a stronger glycolysis ability, which was associated with hexokinase 2 (HK2) overexpression. Additionally, the tumor growth of OSCC cells was delayed in vivo and the glycolysis was notably decreased following HK2 knockdown. The natural compound screening revealed that gastrodin could be an effective candidate for OSCC therapy since it inhibited HK2-mediated glucose metabolism and promoted endogenous OSCC cell apoptosis. Furthermore, gastrodin could bind to protein kinase B (Akt) and suppress its activity, thus downregulating HK2 at the transcriptional level. Additionally, S-phase kinase-associated protein 2 (Skp2) was highly expressed in OSCC cells, while K63-linked ubiquitination of Akt was inhibited in Skp2-depleted cisplatin-resistant OSCC cells. Gastrodin could also inhibit the cisplatin resistance of OSCC cells in vivo, particularly when combined with the Skp2 inhibitor, SZL P1-41. Overall, the aforementioned finding suggested that targeting the Skp2-Akt axis could be a potential therapeutic strategy for treating OSCC and overcoming chemoresistance.

Abstract Background This retrospective multicenter study evaluated the efficacy and safety of bariatric surgery in Chinese patients with obesity. Methods Patients with obesity who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux‐en‐Y gastric bypass and completed a 12‐month follow‐up between February 2011 and November 2019 were enrolled. Weight loss, glycemic and metabolic control, insulin resistance, cardiovascular risk, and surgery‐related complications at 12 months were analyzed. Results We enrolled 356 patients aged 34.3 ± 0.6 years with a mean body mass index of 39.4 ± 0.4 kg/m2. Successful weight loss occurred in 54.6%, 86.8%, and 92.7% of patients at 3, 6, and 12 months, respectively, with no difference in percent excess weight loss between the laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass surgery groups. The average percentage of total weight loss was 29.5% ± 0.6% at 12 months; 99.4%, 86.8%, and 43.5% of patients achieved at least 10%, 20%, and 30% weight loss, respectively, at 12 months. Significant improvements in metabolic indices, insulin resistance, and inflammation biomarkers were observed at 12 months. Conclusions Bariatric surgery resulted in successful weight loss and improved metabolic control, insulin resistance, and cardiovascular risk in Chinese patients with obesity. Both laparoscopic sleeve gastrectomy and laparoscopic Roux‐en‐Y gastric bypass are suitable approaches for such patients.

Objective(s): Liver fibrosis is a common liver disease caused by chronic liver damage. However, there are currently no approved drugs available to treat it. Therefore, the therapeutic effect of indirubin on liver fibrosis was evaluated. This study investigated the protective effect and related molecular mechanism of indirubin against CCl4-induced liver fibrosis in mice.Materials and Methods: We first detected the effect of indirubin on liver fibrosis in mice (n=8 per group, 32 mice total) by ELISA, HE, and Masson staining. Subsequently, the proliferation of activated HSCs was detected by MTT and EdU. Finally, the changes of related proteins and signaling pathways in mice treated with indirubin were investigated by qRT-PCR and Western blot. One-way ANOVA or two-tailed student’s t-test was used for comparison between groups.Results: Firstly, we found that indirubin (25 mg/kg) therapy could attenuate liver injury and significantly down-regulate α-SMA (P=0.0038) and collagen 1 (P=0.0057) in the liver using CCl4-induced liver fibrosis in mice. Secondly, we showed that indirubin (25 μM) could significantly inhibit hepatic stellate cell (HSC) trans-differentiation into myofibroblasts and proliferation (P=0.0063) in HSC-T6 cells treated by TGF-β. Finally, we showed that indirubin could greatly reduce the protein levels of p-Smad2/3, p38, p-ERK, and p-JNK in vivo and in vitro.Conclusion: Our results suggested that indirubin alleviated liver fibrosis and HSC activation mainly through TGF-β-mediated signaling pathways in vivo and in vitro. In conclusion, our data showed that indirubin could be a promising clinical therapeutic drug for the prevention and treatment of liver fibrosis.

Abstract Background Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population. Methods The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL. Results Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL. Conclusions The CD40 gene may play a role in the occurrence and development of CSCC.

Abstract The emergence of caste-differentiated colonies, which have been defined as ‘superorganisms’, in ants, bees, and wasps represents a major transition in evolution. Lifetime mating commitment by queens, pre-imaginal caste determination and lifetime unmatedness of workers are key features of these animal societies. Workers in superorganismal species like honey bees and many ants have consequently lost, or retain only vestigial spermathecal structures. However, bumble bee workers retain complete spermathecae despite 25-40 million years since their origin of superorganismality, which remains an evolutionary mystery. Here, we show (i) that bumble bee workers retain queen-like reproductive traits, being able to mate and produce colonies, underlain by queen-like gene expression, (ii) the social conditions required for worker mating, and (iii) that these abilities may be selected for by early queen-loss in these annual species. These results challenge the idea of lifetime worker unmatedness in superorganisms, and provide an exciting new tool for the conservation of endangered bumble bee species.

Edamame (Glycine max (L.) Merr.) is a specialty soybean newly grown in the United States that has become the second most widely consumed soy food (25,000–30,000 tons annually). Poor crop establishment caused by soilborne diseases is a major problem limiting edamame production in the U.S. This study investigated 24 edamame cultivars/lines to determine their response to three soilborne pathogens causing seed rot and seedling damping off, including Rhizoctonia solani, Sclerotium rolfsii, Pythium irregulare, and Xanthomonas campestris pv. glycines, a seedborne pathogen that caused severe outbreaks of bacterial leaf pustules in mid-Atlantic regions in 2021. The hypothesis was that resistant variations existed among the genotypes, which could be used for production and future breeding efforts. The results reveal that all genotypes were affected, but partially resistant varieties could be clearly recognized by a significantly lower disease index (p < 0.05), and no genotype was resistant to all four diseases. Newly developed breeding lines showed overall higher disease resistance than commercial cultivars, particularly to R. solani and P. irregulare. This study found genetic variability in edamame, which can be helpful in breeding for resistance or tolerance to early-season diseases. The result will promote domestic edamame production and further strengthen and diversify agricultural economies in the U.S.

The possibility of directly growing carbon nanofibers (CNFs) and carbon nanotubes (CNTs) on half-Heusler alloys by Chemical Vapour Deposition (CVD) is investigated for the first time, without using additional catalysts, since the half-Heusler alloys per se may function as catalytic substrates, according to the findings of the current study. As a carbon source, acetylene is used in the temperature range of 700–750 °C. The n-type half-Heusler compound Zr0.4Ti0.60.33Ni0.33Sn0.98Sb0.020.33 is utilized as the catalytic substrate. At first, a computational model is developed for the CVD reactor, aiming to optimize the experimental process design and setup. The experimental process conditions are simulated to investigate the reactive species concentrations within the reactor chamber and the activation of certain reactions. SEM analysis confirms the growth of CNFs with diameters ranging from 450 nm to 1 μm. Raman spectroscopy implies that the formed carbon structures resemble CNFs rather than CNTs, and that amorphous carbon also co-exists in the deposited samples. From the characterization results, it may be concluded that a short reaction time and a low acetylene flow rate lead to the formation of a uniform CNF coating on the surface of half-Heusler alloys. The purpose of depositing carbon nanostructures onto half-Heusler alloys is to improve the current transfer, generated from these thermoelectric compounds, by forming a conductive coating on their surface.

Abstract Background A close connection between a protozoan parasite and the balance of the other gut microbes of the host has been demonstrated. The calves may be naturally co-infected with many parasites, and the co-effects of parasites on other intestinal microbes of calves remain unclear. This study aims to preliminarily reveal the relationship between intestinal parasites and other intestinal microbes in calves. Methods Fecal samples were collected from four calves with bloody diarrhea, four calves with watery diarrhea, and seven normal calves, and the microbial flora of the samples were analyzed by whole-genome sequencing. Protozoal parasites were detected in the metagenome sequences and identified using polymerase chain reaction (PCR). Results Cryptosporidium, Eimeria, Giardia, Blastocystis, and Entamoeba were detected by metagenomic analysis, and the identified species were Giardia duodenalis assemblage E, Cryptosporidium bovis, Cryptosporidium ryanae, Eimeria bovis, Eimeria subspherica, Entamoeba bovis, and Blastocystis ST2 and ST10. Metagenomic analysis showed that the intestinal microbes of calves with diarrhea were disordered, especially in calves with bloody diarrhea. Furthermore, different parasites show distinct relationships with the intestinal microecology. Cryptosporidium, Eimeria, and Giardia were negatively correlated with various intestinal bacteria but positively correlated with some fungi. However, Blastocystis and Entamoeba were positively associated with other gut microbes. Twenty-seven biomarkers not only were significantly enriched in bloody diarrhea, watery diarrhea, and normal calves but were also associated with Eimeria, Cryptosporidium, and Giardia. Only Eimeria showed a distinct relationship with seven genera of bacteria, which were significantly enriched in the healthy calves. All 18 genera of fungi were positively correlated with Cryptosporidium, Eimeria, and Giardia, which were also significantly enriched in calves with bloody diarrhea. Functional genes related to parasites and diseases were found mainly in fungi. Conclusions This study revealed the relationship between intestinal protozoan parasites and the other calf gut microbiome. Different intestinal protozoan parasites have diametrically opposite effects on other gut microecology, which not only affects bacteria in the gut, but also is significantly related to fungi and archaea. Graphical Abstract

Abstract Background Cryptosporidium is second only to rotavirus as a cause of moderate-to-severe diarrhea in young children. There are currently no fully effective drug treatments or vaccines for cryptosporidiosis. MicroRNAs (miRNAs) are involved in regulating the innate immune response to Cryptosporidium parvum infection. In this study, we investigated the role and mechanism of miR-3976 in regulating HCT-8 cell apoptosis induced by C. parvum infection. Methods Expression levels of miR-3976 and C. parvum burden were estimated using real-time quantitative polymerase chain reaction (RT-qPCR) and cell apoptosis was detected by flow cytometry. The interaction between miR-3976 and B-cell lymphoma 2-related protein A1 (BCL2A1) was studied by luciferase reporter assay, RT-qPCR, and western blotting. Results Expression levels of miR-3976 were decreased at 8 and 12 h post-infection (hpi) but increased at 24 and 48 hpi. Upregulation of miR-3976 promoted cell apoptosis and inhibited the parasite burden in HCT-8 cells after C. parvum infection. Luciferase reporter assay indicated that BCL2A1 was a target gene of miR-3976. Co-transfection with miR-3976 and a BCL2A1 overexpression vector revealed that miR-3976 targeted BCL2A1 and suppressed cell apoptosis and promoted the parasite burden in HCT-8 cells. Conclusions The present data indicated that miR-3976 regulated cell apoptosis and parasite burden in HCT-8 cells by targeting BCL2A1 following C. parvum infection. Future study should determine the role of miR-3976 in hosts’ anti-C. parvum immunity in vivo. Graphical Abstract