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BackgroundThe burden of cryptococcosis in mainland China is enormous. However, the in vitro characterization and molecular epidemiology in Guangdong, a key region with a high incidence of fungal infection in China, are not clear.MethodsFrom January 1, 2010, to March 31, 2019, clinical strains of Cryptococcus were collected from six medical centres in Guangdong. The clinical information and characteristics of the strains were analysed. Furthermore, molecular types were determined.ResultsA total of 84 strains were collected, mostly from male and young or middle-aged adult patients. Pulmonary and cerebral infections (82.1%) were most common. All strains were Cryptococcus neoformans, grew well at 37°C and had capsules around their cells. One melanin- and urea- and one melanin+ and urea- variants were found. Although most strains exhibited a low minimum inhibitory concentration (MIC) value for voriconazole (mean: 0.04 μg/mL) and posaconazole (mean: 0.12 μg/mL), the results for these isolates showed a high degree of variation in the MIC values of fluconazole and 5-fluorocytosine, and resistance was observed for 4 out of 6 drugs. A significant proportion of these strains had MIC values near the ECV values, particularly in the case of amphotericin B. The proportion of strains near the clinical breakpoints was as follows: fluconazole: 3.66%; voriconazole: 3.66%; itraconazole: 6.10%; posaconazole: 13.41%; amphotericin B: 84.15%; 5-fluorocytosine: 2.44%. These strains were highly homogeneous and were dominated by the Grubii variant (95.2%), VNI (94.0%), α mating (100%), and ST5 (89.3%) genotypes. Other rare types, including ST4, 31, 278, 7, 57 and 106, were also found.ConclusionPhenotypically variant and non-wild-type strains were found in Guangdong, and a significant proportion of these strains had MIC values near the ECV values towards the 6 antifungal drugs, and resistance was observed for 4 out of 6 drugs. The molecular type was highly homogeneous but compositionally diverse, with rare types found. Enhanced surveillance of the aetiology and evolution and continuous monitoring of antifungal susceptibility are needed to provide references for decision-making in the health sector and optimization of disease prevention and control.

It has become a consensus that large-scale hydraulic fracturing is adopted to achieve the stimulation of unconventional oil and gas reservoir. The complex fracture network formed by fracturing is closely related to the effect of reservoir stimulation, which has extremely complicated evolution process. Therefore, it is necessary to study the evolution law of fracture network in large-scale hydraulic fracturing of unconventional reservoirs. In this article, the geological engineering parameters of horizontal well H in shale gas reservoir in southern Sichuan are taken as an example, a three-dimensional fracture network expansion model is established based on the boundary element method and finite volume method, and the simulation of the complex fracture network in a whole well section is carried out to analyze the evolution law of reservoir fracture network under different geological and engineering parameters. The results show that the horizontal stress field distribution has a significant effect on fracture geometric form. Hydraulic fractures in reservoirs with larger horizontal stress difference have stronger directivity, while the horizontal wellbore tends to obtain better reservoir stimulation results when it is parallel to the minimum horizontal principal stress setting. The conjugated natural fracture developed in the reservoir inhibits the hydraulic expansion fractures in both directions. Although it increases the complexity of the fractures, it is not necessarily conducive to improving the reservoir stimulation effectiveness. The lower the strength of natural fracture is, the more complex the fracture geometric form becomes, and the smaller the stimulated reservoir volume is. Correspondingly, the higher the strength of natural fracture is, the simpler the fracture geometric form becomes, and the larger the stimulated reservoir volume is. Suitable fracturing construction displacement can not only contribute to form a more complex fracture distribution, but also help to obtain a larger stimulated reservoir volume. The optimal construction displacement ranges from 10 to 14 m3/min. Low viscosity fracturing fluids are suitable for the formation of long-narrow fractures and able to connect with the remote reservoir and form complex fracture networks. Lower viscosity fluids can be used to achieve better reservoir stimulation effectiveness when sand-carrying capacity is met.

Artificial Intelligence (AI) is driving advancements across various fields by simulating and enhancing human intelligence. In Natural Language Processing (NLP), transformer models like the Kerformer, a linear transformer based on a kernel approach, have garnered success. However, traditional attention mechanisms in these models have quadratic calculation costs linked to input sequence lengths, hampering efficiency in tasks with extended orders. To tackle this, Kerformer introduces a nonlinear reweighting mechanism, transforming maximum attention into feature-based dot product attention. By exploiting the non-negativity and non-linear weighting traits of softmax computation, separate non-negativity operations for Query(Q) and Key(K) computations are performed. The inclusion of the SE Block further enhances model performance. Kerformer significantly reduces attention matrix time complexity from O(N2) to O(N), with N representing sequence length. This transformation results in remarkable efficiency and scalability gains, especially for prolonged tasks. Experimental results demonstrate Kerformer's superiority in terms of time and memory consumption, yielding higher average accuracy (83.39%) in NLP and vision tasks. In tasks with long sequences, Kerformer achieves an average accuracy of 58.94% and exhibits superior efficiency and convergence speed in visual tasks. This model thus offers a promising solution to the limitations posed by conventional attention mechanisms in handling lengthy tasks.

Image-based identification and quantification of different types of spermatogenic cells is of great importance, not only for reproductive studies but also for genetic breeding. Here, we have developed antibodies against spermatogenesis-related proteins in zebrafish (Danio rerio), including Ddx4, Piwil1, Sycp3, and Pcna, and a high-throughput method for immunofluorescence analysis of zebrafish testicular sections. By immunofluorescence analysis of zebrafish testes, our results demonstrate that the expression of Ddx4 decreases progressively during spermatogenesis, Piwil1 is strongly expressed in type A spermatogonia and moderately expressed in type B spermatogonia, and Sycp3 has distinct expression patterns in different subtypes of spermatocytes. Additionally, we observed polar expression of Sycp3 and Pcna in primary spermatocytes at the leptotene stage. By a triple staining of Ddx4, Sycp3, and Pcna, different types/subtypes of spermatogenic cells were easily characterized. We further demonstrated the practicality of our antibodies in other fish species, including Chinese rare minnow (Gobiocypris rarus), common carp (Cyprinus carpio), blunt snout bream (Megalobrama amblycephala), rice field eel (Monopterus albus) and grass carp (Ctenopharyngodon idella). Finally, we proposed an integrated criterion for identifying different types/subtypes of spermatogenic cells in zebrafish and other fishes using this high-throughput immunofluorescence approach based on these antibodies. Therefore, our study provides a simple, practical, and efficient tool for the study of spermatogenesis in fish species.

In tight gas reservoirs, the major flow channels are composed of micro/nanopores in which the rarefaction effect is prominent and the traditional Darcy law is not appropriate for gas flow. By combining the Maxwell first-order slip boundary condition and Navier–Stokes equations, a three-dimensional (3D) analysis of compressible gas slip flow in a microtube was presented, and the flux rate and pressure variation in the flow direction were discussed. Subsequently, by superimposing the Knudsen diffusion, a gas flux formula applicable to a larger Knudsen number was further proposed and satisfactorily verified by two groups of published experimental data in microtubes or microchannels in the membrane. The results indicate that slip flow and Knudsen diffusion make an important contribution to the total gas flow in the microtube, and their weight increases with an increase in the Knudsen number. By substituting the gas flux formula into Darcy’s law for compressible gas, a new apparent permeability model for tight gas reservoirs was proposed, in which the slippage effect and Knudsen diffusion were synthetically considered. The results indicate that the apparent permeability of tight reservoirs strongly depends on the reservoir pressure and pore-throat radius, and an underestimation value may be predicted by the previously published models. This study provides a case study for evaluating these apparent permeability models, which remains a challenging task in the laboratory.

Field production data indicate that the shale gas production rate decreases sharply after a few years of the first fracking. Feasible enhanced gas recovery (EGR) approaches are very necessary to be investigated. In this study, we compared re-fracturing with a huff-n-puff gas injection scheme in a shale gas reservoir for EGR. A fully compositional simulation approach coupled with a dual porosity and dual permeability model is used. The gas production performances by using different fracturing fluids (i.e., slickwater and supercritical CO2) are evaluated. The effects of huff-n-puff parameters and matrix permeability on the gas production rate and carbon sequestration are investigated. The results show that using a re-fracturing approach yields a better recovery performance than the huff-n-puff gas injection method. Re-fracturing using supercritical CO2 performs better than using slickwater because the former can create complex three-dimensional fracture networks. Huff-n-puff CO2 injection can enhance the gas recovery effectively in ultra-tight formations. In a relatively high permeable formation, viscous flow instead of adsorption-desorption isotherms becomes the primary mass transfer mechanisms, resulting in a lower gas recovery. Both the re-fracturing treatment and huff-n-puff CO2 injection are profitable from a long-term cash flowback perspective.

IntroductionSARS-CoV-2 has ravaged the world and undergone multiple mutations during the course of the COVID-19 pandemic. On 7 April 2022, an epidemic caused by SARS-CoV-2 Omicron (BA.2) variant broke out in Guangzhou, China, one of the largest transportation and logistical hubs of the country.MethodsTo fast curtained the Omicron epidemic, based on the routine surveillance on the risk population of SARS-CoV-2 infection, we identify key places of the epidemic and implement enhanced control measures against Omicron.ResultsTransmission characteristics of the Omicron variant were analyzed for 273 confirmed cases, and key places involved in this epidemic were fully presented. The median incubation time and the generation time were 3 days, and the reproduction number Rt was sharply increased with a peak of 4.20 within 2 days. We tried an all-out effort to tackle the epidemic in key places, and the proportion of confirmed cases increased from 61.17% at Stage 2 to 88.89% at Stage 4. Through delimited risk area management, 99 cases were found, and the cases were isolated in advance for 2.61 ± 2.76 days in a lockdown zone, 0.44 ± 1.08 days in a controlled zone, and 0.27 ± 0.62 days in a precautionary zone. People assigned with yellow code accounted for 30.32% (84/277) of confirmed COVID-19 cases, and 83.33% of them were detected positive over 3 days since code assignment. For the districts outside the epicenter, the implementation duration of NPIs was much shorter compared with the Delta epidemic last year.ConclusionBy blocking out transmission risks and adjusting measures to local epidemic conditions through the all-out effort to tackle the epidemic in key places, by delimiting risk area management, and by conducting health code management of the at-risk population, the Omicron epidemic could be contained quickly.

Growth hormone (GH) is important for regulating insulin secretion and carbohydrate metabolism, and its role in mammalian models of diabetes is relatively worked out. Although some fish species were used as models for diabetes research, the effects of GH on insulin and glucose catabolism and anabolism in these models remain to be clarified. In this study, we investigated the effect of GH on insulin and glucose catabolism and anabolism in an omnivorous fish using GH transgenic (T) common carp that consistently overexpressed GH and wild-type (WT) common carp. We compared the intestinal morphology, and digestive and absorptive capacity of fish fed commercial feed. We also analyzed the growth performance, insulin level, glucose catabolism and anabolism, lipid deposition, and lipid catabolism and anabolism in T carp and WT carp fed diets containing either 30% or 40% starch. In the intestine of T carp, α-amylase activity was enhanced, the number of goblet cells and intestinal villi surface area was increased, and the expression level of glucose transport protein-related genes (glut2 and sglt1) was upregulated when compared to these indicators in WT carp. When fed either a normal or high-starch diet, the growth performance of T carp was better than that of WT carp. Compared with WT carp, serum insulin was increased and glucose was decreased, hepatic expression level of igf-1 and glycolysis-related genes was increased, and the activity level of a hepatic enzyme related to glycolysis was enhanced in T carp. When fed with a high-starch diet, the serum alanine aminotransferase activity, hepatic lipid content, and malondialdehyde content were significantly lower in T carp than in WT carp. These results indicated that overexpression of GH (1) enhanced carbohydrate digestion and absorption in the carp intestine, (2) did not induce insulin resistance and improved glucose catabolism and utilization in carp, and (3) relieved liver lipid deposition. Our data might provide new insights into potential ways to improve glucose utilization in fish and diabetes treatments.

Allicin, which is generated by the catalytic reaction between alliin and alliinase extracted from garlic, has been shown to have a wide range of antimicrobial activities, but its anti-Cryptococcus efficacy and mechanism are not quite clear. Here, we have determined that the Conversion rate of allicin in the reaction product reached 97.5%. The minimal inhibitory concentration (MIC) of allicin against Cryptococcus neoformans (C. neoformans) H99 was 2 μg/ml, which is comparable to fluconazole (FLU, 1 μg/ml). Furthermore, allicin exhibited effective antifungal activity against 46 clinical isolates of C. neoformans, and the MICs ranged from 1 to 8 μg/ml, even for AmB-insensitive strains. Interestingly, allicin also exerted additive or synergistic effects when combined with amphotericin B (AmB) and FLU. Time-killing curves and long-term live cell imaging of H99 showed that 4 MIC of allicin had fungicide activity. Additionally, allicin (4 and 8 mg/kg) exerted a dose-dependent therapeutic effect on H99-infected mice by significantly reducing the wet pulmonary coefficient and Cryptococcus load and reducing lung damage. Even the efficacy of 8 mg/kg was comparable to FLU (20 mg/kg). Transcriptomics revealed that allicin may act on the cell membrane of H99. Subsequently, transmission electron microscopy (TEM) observations showed that allicin clearly breached the cell membrane and organelles of H99. Confocal laser scanning microscopy (CLSM) results further confirmed that allicin disrupted the permeability of the cell membranes of H99 in a dose-dependent manner. Allicin exhibits strong anti-C. neoformans activity in vitro and in vivo, mainly by destroying the permeability and related functions of Cryptococcus cell membranes.

Distributions of pore pressure and water saturation in matrix around fractures after hydraulic fracturing and shut-in period will impact the shale gas well production significantly. However, the influences of hydraulic fracturing and shut-in period on pore pressure and water saturation are not considered in the classical reservoir simulations. In this work, the embedded discrete fracture model (EDFM), which is convenient to be coupled with an existing reservoir simulator with high computational efficiency, was employed to simulate the hydraulic fracture propagation coupled with matrix flow. Then, we developed a model for simulating the integration process of hydraulic fracturing, shut-in period, and well production based on the dual media theory. Distributions of pore pressure and water saturation varying in different periods and the production decline of shale gas well were obtained through the integrated simulation model. The calculation result was validated by the field bottom hole pressure data of a shale gas well in Sichuan Province, China. Simulation results show that the variation of bottom hole pressure is not smooth during the fracture propagation process because the initiations of different fractures are not simultaneous. The fracturing fluid flow-back rate of shale gas well is much lower than that of conventional reservoirs. There is still a large amount of fracturing fluid retained in micro-fracture systems and matrix of shale after production. It is also found that the permeability of the micro-fracture system determines the drop rate of bottom hole pressure and the size of stimulated reservoir volume (SRV) determines the decrease amplitude of bottom hole pressure.

Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC). During TACE, chemotherapeutic agents are locally infused into the tumor and simultaneously cause hypoxia in tumor cells. Importantly, the poor effect of TACE in some HCC patients has been shown to be related to dysregulated expression of hypoxia-related genes (HRGs). Therefore, we identified 33 HRGs associated with TACE (HRGTs) by differential analysis and characterized the mutational landscape of HRGTs. Among 586 HCC patients, two molecular subtypes reflecting survival status were identified by consistent clustering analysis based on 24 prognosis-associated HRGs. Comparing the transcriptomic difference of the above molecular subtypes, three molecular subtypes that could reflect changes in the immune microenvironment were then identified. Ultimately, four HRGTs (CTSO, MMP1, SPP1, TPX2) were identified based on machine learning approachs. Importantly, risk assessment can be performed for each patient by these genes. Based on the parameters of the risk model, we determined that high-risk patients have a more active immune microenvironment, indicating “hot tumor” status. And the Tumor Immune Dysfunction and Exclusion (TIDE), the Cancer Immunome Atlas (TCIA), and Genome of Drug Sensitivity in Cancer (GDSC) databases further demonstrated that high-risk patients have a positive response to immunotherapy and have lower IC50 values for drugs targeting cell cycle, PI3K/mTOR, WNT, and RTK related signaling pathways. Finally, single-cell level analysis revealed significant overexpression of CTSO, MMP1, SPP1, and TPX2 in malignant cell after PD-L1/CTLA-4 treatment. In conclusion, Onco-Multi-OMICS analysis showed that HRGs are potential biomarkers for patients with refractory TACE, and it provides a novel immunological perspective for developing personalized therapies.

Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid β-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 ± 0.32 g) and WT (initial weight 3.30 ± 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 ± 0.33 g) and WT (initial weight 3.27 ± 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid β-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.

More than 405 million people have contracted coronavirus disease 2019 (COVID-19) worldwide, and mycotic infection may be related to COVID-19 development. There are a large number of reports showing that COVID-19 patients with mycotic infection have an increased risk of mortality. However, whether mycotic infection can be considered a risk factor for COVID-19 remains unknown. We searched the PubMed and Web of Science databases for studies published from inception to December 27, 2021. Pooled effect sizes were calculated according to a random-effects model or fixed-effect model, depending on heterogeneity. We also performed subgroup analyses to identify differences in mortality rates between continents and fungal species. A total of 20 articles were included in this study. Compared with the controls, patients with mycotic infection had an odds ratio (OR) of 2.69 [95% confidence interval (CI): 2.22–3.26] for mortality and an OR of 2.28 (95% CI: 1.65–3.16) for renal replacement therapy (RRT). We also conducted two subgroup analyses based on continent and fungal species, and we found that Europe and Asia had the highest ORs, while Candida was the most dangerous strain of fungi. We performed Egger's test and Begg's test to evaluate the publication bias of the included articles, and the p-value was 0.423, which indicated no significant bias. Mycotic infection can be regarded as a risk factor for COVID-19, and decision makers should be made aware of this risk.

The research area of tight sandstone oil reservoirs was selected, a numerical model of the oil reservoir was developed, and a study of the development options and influencing factors was carried out to analyze the influence of different development methods, physical and engineering parameters on the development dynamics. Study shows that the two main factors limiting the efficient development of tight sandstone reservoirs are reservoir properties and formation energy. Fractured horizontal well injection huff and puff development can effectively improve reservoir physical properties and timely replenish formation energy, which is suitable for the development of such oil reservoirs. In dense sandstone reservoirs, its impact on production capacity is also relatively small when the permeability ratio is small. Due to both gravity and reservoir physical properties, the permeability ratio increases, the cumulative oil production of positive rhythm reservoirs decreases and that of reverse rhythm reservoirs increases, and the location of high-quality reservoirs in the upper part of producing wells is conducive to increasing the final recovery rate. A lower oil to water viscosity ratio can significantly increase the swept volume and improve development effect. Hydrophilic reservoirs can reduce the injection pressure and increase the spread range, effectively improving the problem of inability to inject, and improving reservoir hydrophilicity through surface activators can increase reservoir recovery. The water injection rate determines the recovery rate of formation energy. Generally, the faster the rate, the higher the cumulative oil production. Therefore, the rate of water injection should be increased as much as possible, taking into account construction conditions and economic evaluation. Additionally, the effect of water injection on the development effect is different at different stages, so the appropriate timing of water injection is very important to the water injection huff and puff development effect, and the use of early water injection in this research area is not conducive. Soaking can promote pressure and fluid redistribution and improve water injection huff and puff development effect, but soaking for a long time can lead to reservoir contamination and reduce crude oil production, so the preferred time for a soaking is about 20 days.

SERPINA1, a member of the serine protease inhibitor family, plays a role in viral infection and inflammation by regulating the activities of serine and cysteine proteases. To date, there have been no reports on the immune function of SERPINA1 in fishes. In this study, we first cloned the serpina1 gene of grass carp (Ctenopharyngodon idellus) and found that it could respond rapidly to the infection of Grass carp reovirus (GCRV), and overexpression of serpina1 could enhance the antiviral response of CIK cells. A polyclonal antibody of SERPINA1 was prepared, and the protein interacting with SERPINA1 was screened by CoIP/MS in grass carp hepatopancreas tissue. It was found that SERPINA1 interacted with coagulation factor 2 (CF2) and could degrade it in a dose-dependent manner. In addition, overexpression of cf2 contributed to the infection of GCRV in CIK cells, whereas co-expression of serpina1 and cf2 in grass carp reduced the copy number of GCRV in cells. The results showed that grass carp SERPINA1 could inhibit GCRV infection by degrading CF2. This study proposes that SERPINA1 can inhibit viral infection through interaction with the coagulation factor, providing new insights into the molecular mechanism of SERPINA1’s antiviral function.

Realgar- and cinnabar-containing AnGongNiuHuang Pill (AGNHP) is widely used for treating encephalopathy syndrome. However, it raises great safety concerns due to the adverse effects reported by arsenic or mercury poisoning. Although AGNHP has been generally recognized, little is known about the metabolism of arsenic and mercury and their resulting potential health risk in vivo. Thus, comparative pharmacokinetics and urinary excretion of arsenic and mercury were conducted in rats after oral administration of realgar, cinnabar and AGNHP, respectively. The contents of arsenic and mercury in rat blood and urine were determined by hydride-generation atomic fluorescence spectrometry (HG-AFS) after wet digestion. AGNHP significantly reduced the absorption of arsenic in blood and promoted urinary arsenic excretion. Whereas, it increased the blood mercury absorption and reduced urinary mercury excretion. No significant toxicity was observed in the clinical dose range of AGNHP. However, excessive exposure to arsenic and mercury may still pose risks especially by long-term or excessive medication. The results are helpful for the rational clinical applications of realgar- and cinnabar-containing TCMs.

Various bacterial diseases have caused great economic losses to the high-density and intensive aquaculture industry; however, the pathogenic mechanism underlying the large-scale challenged to caused by many bacteria remain unclear, making the prevention and treatment of these diseases difficult. In the present study, we isolated a bacterial strain from Cyprinus carpio having a typical bacterial disease and named it Cc2021. Through subsequent morphological observations, a regression challenge, biochemical identification, and 16S rRNA gene sequence analysis, we determined Cc2021 to be Plesiomonas shigelloides. Subsequently, we comprehensively investigated the pathogenicity of P. shigelloides in C. carpio through a regression challenge and assessed the underlying the pathogenic mechanism. Mortality results revealed that P. shigelloides is highly pathogenic and infects various tissues throughout the body, resulting in edema of the liver, spleen, and body and head kidneys. Histopathological analysis revealed obvious inflammation, bleeding, and necrosis in the intestine, spleen, and head kidney. The body’s immune tissues actively produce complement C3, superoxide dismutase, and lysozyme after a challenge to resist bacterial invasion. With regard to the underlying pathogenesis of P. shigelloides, comparative transcriptome analysis revealed 876 upregulated genes and 828 downregulated genes in the intestine of C. carpio after the challenge. Analysis of differentially expressed unigenes revealed the involvement of major immune pathways, particularly the TNF signaling pathway, interleukin (IL)-17 signaling pathway, and Toll-like receptor signaling pathway. The present study provides new valuable information on the immune system and defense mechanisms of P. shigelloides.

The borderless transmission of coronavirus remains uncontrolled globally. The uncharted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant reduces the therapeutic efficacy of vaccines against coronavirus disease 2019 (COVID-19). Clinical observations suggest that tumour cases are highly infected with coronavirus, possibly due to immunologic injury, causing a higher COVID-19-related death toll. Presently, screening of candidate medication against coronavirus is in progress. Mogroside V, a bioactive ingredient of Siraitia grosvenorii, has been reported in China to have lung-protective and anticancer effects. The current study used network pharmacology and molecular docking to unlock the potential drug targets and remedial mechanisms of mogroside V against patients with ovarian cancer with COVID-19. We identified 24 related targets of mogroside V in patients with ovarian cancer and COVID-19 and characterised another 10 core targets of mogroside V against COVID-19 ovarian cancer, including Jun, IL2, HSP90AA1, AR, PRKCB, VEGFA, TLR9, TLR7, STAT3, and PRKCA. The core targets’ biological processes and signalling pathways were revealed by enrichment analysis. Molecular docking suggested favourable docking between core target protein and mogroside V, including vascular endothelial growth factor A (VEGFA). These findings indicated that mogroside V might be a potential therapeutic agent in the mitigation of COVID-19 ovarian cancer.

The common carp (Cyprinus carpio) accounts for approximately 10% of the annual freshwater aquaculture production and is an ideal model to study cyprinidae reproduction. Female common carp grow faster than the males; therefore, related research presents an opportunity with high application value. Although we have a detailed understanding of common carp’s early gonadal differentiation process, information about genome-wide gene expression, regulation, and underlying molecular mechanisms during this process remain limited. Here, time-course data comprising six key stages during testicular differentiation and maturation were investigated to further understand the molecular mechanisms underlying the testicular development in cyprinid species. After integrating these time-series data sets, common carp genome, including 98,345 novel transcripts and 3,071 novel genes were re-annotated and precisely updated. Gene co-expression network analysis revealed that the ubiquitin-mediated proteolysis pathway was essential for metabolism during testicular differentiation in the endocrine system of C. carpio. Functional enrichment analyses indicated that genes mainly related to amino acid metabolism and steroid hormone synthesis were relatively highly expressed at the testicular undifferentiation stages, whereas genes associated with cell cycle and meiosis were expressed from the beginning of testicular differentiation until maturation. The dynamics of alternative splicing events demonstrated that exon skipping accounted for majority of the alternative splicing events in the testis and the brain during gonad development. Notably, several potential male-specific genes (fanci and sox30) and brain-specific genes (oxt, gad2, and tac1, etc.) were identified. Importantly, we traversed beyond the level of transcription to test for stage- and gonad-specific alternative splicing patterns between the brain and testis. This study is the first to describe a comprehensive landscape of alternative splicing events and gene expression patterns during gonadogenesis in common carp. This work is extremely valuable to elucidate the mechanisms underlying gonadal differentiation in Cyprinidae as well as other fish species.

PurposeThe aim of this study was to investigate the physiological and perceptional responses to forward, forward-backward, and lateral shuttle running.MethodsTwenty-four eligible male subjects performed a maximal oxygen uptake (VO2max) test and three directional modes (i.e., forward, forward-backward, and lateral) of 5-m shuttle running at the speed of 6 km⋅h–1 for 5 min on separate days. Heart rate (HR) and oxygen uptake (VO2) were continuously measured during the whole tests. Rating of perceived exertion (RPE) was inquired and recorded immediately after the test. Capillary blood samples were collected from the earlobe during the recovery to determine the peak value of blood lactate concentration ([La–]peak).ResultsRunning directional mode had significant effects on HR (F = 72.761, P < 0.001, η2p = 0.760), %HRmax (F = 75.896, P < 0.001, η2p = 0.767), VO2 (F = 110.320, P < 0.001, η2p = 0.827), %VO2max (F = 108.883, P < 0.001, η2p = 0.826), [La–]peak (F = 55.529, P < 0.001, η2p = 0.707), and RPE (F = 26.268, P < 0.001, η2p = 0.533). All variables were significantly different between conditions (P ≤ 0.026), with the variables highest in lateral shuttle running and lowest in forward shuttle running. The effect sizes indicated large magnitude in the differences of all variables between conditions (ES = 0.86–2.83, large) except the difference of RPE between forward and forward-backward shuttle running (ES = 0.62, moderate).ConclusionThese findings suggest that the physiological and perceptional responses in shuttle running at the same speed depend on the directional mode, with the responses highest in lateral shuttle running, and lowest in forward shuttle running.

Exosomes are membrane extracellular vesicles secreted by almost all kinds of cells, which are rich in proteins, lipids, and nucleic acids. As a medium of intercellular communication, exosomes play important roles in biological processes and are closely related to the occurrence, and development of many diseases. The isolation of exosomes and downstream analyses can provide important information to the accurate diagnosis and treatment of diseases. However, exosomes are various in a size range from 30 to 200 nm and exist in complex bio-systems, which provide significant challenges for the isolation and enrichment of exosomes. Different methods have been developed to isolate exosomes, such as the “gold-standard” ultracentrifugation, size-exclusion chromatography, and polymer precipitation. In order to improve the selectivity of isolation, affinity capture strategies based on molecular recognition are becoming attractive. In this review, we introduced the main strategies for exosome isolation and enrichment, and compared their strengths and limitations. Furthermore, combined with the excellent performance of targeted peptides, we summarized the application of peptide recognition in exosome isolation and engineering modification.

Most studies investigating mental fatigue (MF) in soccer utilized a computerized Stroop task to induce MF. However, the traditional key-pressing task has been challenged for its lack of ecological validity. The limited relevance to real-life soccer made it difficult to bridge the gap between the research and the applied setting. Therefore, a novel soccer-specific inducing task is in urgent need. This study compared a novel MF-inducing task in soccer with the Stroop task and investigated the impact of induced MF on cognitive and soccer-specific skill performance. A randomized, counterbalanced crossover design was employed. Fifteen well-trained male soccer players randomly participated in three MF-inducing tasks. Two of them were motor tasks consisting of 10 repeated interval Loughborough Soccer Passing Test (10xLSPT or LSPT) in clockwise passing order (10xC-LSPT) with each block starting every 2 min. The two tasks share the same movement pattern, but C-LSPT is considered to have lower cognitive demands. The third was the 20-min Stroop task (Stroop-20). MF was assessed immediately before and after each task by visual analog scale (VAS), the cognitive performance in a 3-min Stroop task, and the skill performance in one LSPT. Subjective MF increased similarly after 10xLSPT and Stroop-20 (+ 25.4 ± 10.3 vs. + 23.4 ± 10.8 AU, p = 0.607). The induced MF by 10xLSPT and Stroop-20 had no impact on cognitive performance and movement time but similarly affected in a significantly negative manner on penalty time (+ 5.9 ± 4.9 vs. + 5.4 ± 4.2 s, p = 0.748) and passing accuracy (–1.4 ± 1.5 vs. –1.0 ± 1.3, p = 0.465). Two motor tasks shared similar intensity, but 10xC-LSPT was inefficient to induce MF. The results showed that the 20-min repeated interval LSPT could induce a similar MF as the Stroop task. The induced MF had detrimental effects on soccer skill performance. The novel motor task is recommended for MF studies in soccer as an inducement task. Practitioners should be cautious about the prolonged cognitive-demanding skill section of the pre-match warm-up to avoid the negative effect of MF on the upcoming match. This motor task pattern could be followed as a supplementary training protocol.

BackgroundClinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis.MethodsThe clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB.ResultsThe bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU).ConclusionsBased on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

Purpose: The aim of this study was to explore the validity and reliability of a phone app [named: change of direction (COD) timer] and stopwatches for the measurement of COD performance.Methods: Sixty-two youth basketball players (age: 15.9±1.4yrs., height: 178.8±11.0cm, and body mass: 70.0±14.1kg) performed six trials of 505 COD test (with the left side being the plant leg first, then the right side). The completion time was measured simultaneously via timing gates (with error correction processing algorithms), the phone app, and stopwatches.Results: There was an almost perfect correlation and agreement between timing gates and COD timer (r=0.978; SEE=0.035s; and LoA=−0.08~0.06s), but a lower correlation and agreement between timing gates and stopwatch (r=0.954; SEE=0.050s; and LoA=−0.17~0.04s) with statistical significance in completion time (ES=1.29, 95%CI: 1.15–1.43, p

Grass carp (Ctenopharyngodon idellus) is an important aquaculture species in China that is affected by serious diseases, especially hemorrhagic disease caused by grass carp reovirus (GCRV). Grass carp have previously shown age-dependent susceptibility to GCRV, however, the mechanism by which this occurs remains poorly understood. Therefore, we performed transcriptome and metabolome sequencing on five-month-old (FMO) and three-year-old (TYO) grass carp to identify the potential mechanism. Viral challenge experiments showed that FMO fish were susceptible, whereas TYO fish were resistant to GCRV. RNA-seq showed that the genes involved in immune response, antigen presentation, and phagocytosis were significantly upregulated in TYO fish before the GCRV infection and at the early stage of infection. Metabolome sequencing showed that most metabolites were upregulated in TYO fish and downregulated in FMO fish after virus infection. Intragroup analysis showed that arachidonic acid metabolism was the most significantly upregulated pathway in TYO fish, whereas choline metabolism in cancer and glycerophospholispid metabolism were significantly downregulated in FMO fish after virus infection. Intergroup comparison revealed that metabolites from carbohydrate, amino acid, glycerophospholipid, and nucleotide metabolism were upregulated in TYO fish when compared with FMO fish. Moreover, the significantly differentially expressed metabolites showed antiviral effects both in vivo and in vitro. Based on these results, we concluded that the immune system and host biosynthesis and metabolism, can explain the age-dependent viral susceptibility in grass carp.

PurposeThe aim of this study was to compare the energy contributions and workloads in men and women during badminton matches versus frequently used multi-ball smash practices.MethodsFourteen badminton players performed one badminton singles game and one session of smashing practice on separate days. The energy contributions were examined in terms of each individual’s three energy systems and substrate oxidation, while workloads included heart rate (HR), Player Load (PL), accelerations, decelerations, changes of direction, and jumps.Results(1) During games, male players exhibited higher adenosine triphosphate–phosphocreatine system contribution (EPCr, kJ) (p = 0.008) and average rate of carbohydrate oxidation (RCHO, g/min) (p = 0.044) than female players, while female players showed greater absolute PL (p = 0.029) and more accelerations (p = 0.005) than male players. Furthermore, players who lost performed higher relative PL (p = 0.017) than those who won. (2) Higher energy system contributions, including EPCr (kJ) (p = 0.028), EHLa (kJ) (p = 0.024), EAer (kJ) (p = 0.012), ETot (kJ) (p = 0.007), and RCHO (g/min) (p = 0.0002), were seen in male players during repetitive spike practices. Male players also made greater number of jumps (p = 0.0002). (3) Players exhibited higher aerobic energy contribution (p < 0.001), mean HR (p = 0.002), and HRmax (p = 0.029) during games, while exhibiting greater anaerobic energy contribution (p < 0.001) and relative PL (p = 0.001) during repetitive practices.ConclusionThe similarities between male and female badminton players in proportional use of the three energy systems during games and repetitive spike training indicate similar relative energy demands for both genders. However, considering the need for higher aerobic capacity in competition, it might be advisable to design appropriate work:rest ratios for repetitive practices in daily training.

Increasing attention has been directed to Talaromyces marneffei (T. marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. marneffei infection in HIV-negative patients.

Objectives: Autism spectrum disorders (ASD) are neurodevelopmental disorders with changes in the gut and oral microbiota. Based on the intimate relationship between the oral microbiota and oral mucosal immunity, this study aimed to investigate changes in salivary immunoglobulin A (IgA) level in ASD and the underlying mechanism for any such changes.Methods: We recruited 36 children diagnosed with ASD and 35 normally developing children and measured their salivary IgA content using enzyme-linked immunosorbent assay (ELISA). The valproate (VPA) -treated ASD mouse model was established by prenatal exposure to valproate and mouse salivary IgA content was also quantified by ELISA. The submandibular glands of VPA and control mice were isolated and analyzed using qRT-PCR, immunofluorescence staining, and flow cytometry. ASD-related Streptococci were co-incubated with the human salivary gland (HSG) cell line, and western blotting was used to detect the levels of relevant proteins.Results: We found that salivary IgA content was significantly decreased in patients with ASD and had a significant ASD diagnostic value. The salivary IgA content also decreased in VPA mice and was significantly correlated with autistic-like behaviors among them. The mRNA and protein levels of the polymeric immunoglobulin receptor (Pigr) were downregulated in the submandibular glands of VPA mice and the Pigr mRNA level was positively correlated with mouse salivary IgA content. HSG cells treated with ASD-related Streptococci had reduced PIGR protein level.Conclusion: Therefore, protective IgA levels were reduced in the saliva of individuals with ASD, which correlated with the bacteria-induced downregulation of Pigr in salivary glands. This study suggests a new direction for ASD diagnosis and prevention of oral diseases in ASD cohorts and provides evidence for the ASD mucosal immunophenotype in the oral cavity.

Research on undersampled magnetic resonance image (MRI) reconstruction can increase the speed of MRI imaging and reduce patient suffering. In this paper, an undersampled MRI reconstruction method based on Generative Adversarial Networks with the Self-Attention mechanism and the Relative Average discriminator (SARA-GAN) is proposed. In our SARA-GAN, the relative average discriminator theory is applied to make full use of the prior knowledge, in which half of the input data of the discriminator is true and half is fake. At the same time, a self-attention mechanism is incorporated into the high-layer of the generator to build long-range dependence of the image, which can overcome the problem of limited convolution kernel size. Besides, spectral normalization is employed to stabilize the training process. Compared with three widely used GAN-based MRI reconstruction methods, i.e., DAGAN, DAWGAN, and DAWGAN-GP, the proposed method can obtain a higher peak signal-to-noise ratio (PSNR) and structural similarity index measure(SSIM), and the details of the reconstructed image are more abundant and more realistic for further clinical scrutinization and diagnostic tasks.

Growth and reproduction are closely related. Growth hormone (GH)-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and in vitro incubation. The expression of gys (glycogen synthase) and igfbp1 (insulin-like growth factor binding protein) as well as blood glucose concentrations are lower in GH-transgenic carp. Agrp1 (agouti-related protein 1) and sla (somatolactin a), which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2), gthα (gonadotropin hormone, alpha polypeptide), fshβ (follicle stimulating hormone, beta polypeptide), lhβ [luteinizing hormone, beta polypeptide] in the pituitary, cyp19a1a (aromatase A) in the gonad, and cyp19a1b (aromatase B) in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih (gonadotropin inhibitory hormone), drd1 (dopamine receptor D1), drd3 (dopamine receptor D3), and drd4 (dopamine receptor D4) exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence in situ hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthα, fshβ, lhβ expression, and ovarian germinal vesicle breakdown in vitro. In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the pituitary might be part of the response to overexpression of GH and the resulting delay in puberty onset.

SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice. Lentiviral vector-mediated overexpression of SIRT6 upregulated TERT and TRF1 and increased the survival of mice after TAC. Echocardiography and hemodynamic measurements as well as histological analyses indicated that SIRT6 overexpression attenuated TAC-induced heart dysfunction and decreased TAC-induced cardiac inflammatory responses, reducing cardiac fibrosis and decreasing infarct size. Taken together, our findings indicate that SIRT6 protects the myocardium against damage and this effect may be mediated by the modulation of telomeres. Our findings linking SIRT6 and telomere integrity in the heart warrant further investigation into the underlying mechanisms and support SIRT6 as a promising therapeutic target for the treatment of cardiovascular diseases.

ObjectiveTo investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment.MethodsThe serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared.ResultsThe incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P

Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid p-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 ± 0.32 g) and WT (initial weight 3.30 ± 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 ± 0.33 g) and WT (initial weight 3.27 ± 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid p-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species. [ABSTRACT FROM AUTHOR]

BackgroundKnee Osteoarthritis (KOA) is a prevalent and debilitating condition affecting millions worldwide, yet its underlying etiology remains poorly understood. Recent advances in neuroimaging and genetic methodologies offer new avenues to explore the potential neuropsychological contributions to KOA. This study aims to investigate the causal relationships between brain-wide morphometric variations and KOA using a genetic epidemiology approach.MethodLeveraging data from 36,778 UK Biobank participants for human brain morphometry and 487,411 UK Biobank participants for KOA, this research employed a two-sample Mendelian Randomization (TSMR) approach to explore the causal effects of 83 brain-wide volumes on KOA. The primary method of analysis was the Inverse Variance Weighted (IVW) and Wald Ratio (WR) method, complemented by MR Egger and IVW methods for heterogeneity and pleiotropy assessments. A significance threshold of p < 0.05 was set to determine causality. The analysis results were assessed for heterogeneity using the MR Egger and IVW methods. Brain-wide volumes with Q_pval < 0.05 were considered indicative of heterogeneity. The MR Egger method was employed to evaluate the pleiotropy of the analysis results, with brain-wide volumes having a p-value < 0.05 considered suggestive of pleiotropy.ResultsOur findings revealed significant causal associations between KOA and eight brain-wide volumes: Left parahippocampal volume, Right posterior cingulate volume, Left transverse temporal volume, Left caudal anterior cingulate volume, Right paracentral volume, Left paracentral volume, Right lateral orbitofrontal volume, and Left superior temporal volume. These associations remained robust after tests for heterogeneity and pleiotropy, underscoring their potential role in the pathogenesis of KOA.ConclusionThis study provides novel evidence of the causal relationships between specific brain morphometries and KOA, suggesting that neuroanatomical variations might contribute to the risk and development of KOA. These findings pave the way for further research into the neurobiological mechanisms underlying KOA and may eventually lead to the development of new intervention strategies targeting these neuropsychological pathways.

Background: Kidney renal clear cell carcinoma (KIRC) is a common and clinically significant subtype of kidney cancer. A potential therapeutic target in KIRC is disulfidptosis, a novel mode of cell death induced by disulfide stress. The aim of this study was to develop a prognostic model to explore the clinical significance of different disulfidptosis gene typings from KIRC.Methods: A comprehensive analysis of the chromosomal localization, expression patterns, mutational landscape, copy number variations, and prognostic significance of 10 disulfide death genes was conducted. Patients were categorized into distinct subtypes using the Non-negative Matrix Factorization (NMF) typing method based on disulfidptosis gene expression patterns. Weighted Gene Co-expression Network Analysis (WGCNA) was used on the KIRC dataset to identify differentially expressed genes between subtype clusters. A risk signature was created using LASSO-Cox regression and validated by survival analysis. An interaction between risk score and immune cell infiltration, tumor microenvironment characteristics and pathway enrichment analysis were investigated.Results: Initial findings highlight the differential expression of specific DRGs in KIRC, with genomic instability and somatic mutation analysis revealing key insights into their role in cancer progression. NMF clustering differentiates KIRC patients into subgroups with distinct survival outcomes and immune profiles, and hierarchical clustering identifies gene modules associated with key biological and clinical parameters, leading to the development of a risk stratification model (LRP8, RNASE2, CLIP4, HAS2, SLC22A11, and KCTD12) validated by survival analysis and predictive of immune infiltration and drug sensitivity. Pathway enrichment analysis further delineates the differential molecular pathways between high-risk and low-risk patients, offering potential targets for personalized treatment. Lastly, differential expression analysis of model genes between normal and KIRC cells provides insights into the molecular mechanisms underlying KIRC, highlighting potential biomarkers and therapeutic targets.Conclusion: This study contributes to the understanding of KIRC and provides a potential prognostic model using disulfidptosis gene for personalized management in KIRC patients. The risk signature shows clinical applicability and sheds light on the biological mechanisms associated with disulfide-induced cell death.

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuV may show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there are many efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton’s resilience against CLCuD.

BackgroundAlthough subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography.MethodsThis meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle–Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models.ResultsSeventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e’ wave (E/e’) had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine.ConclusionIn adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083).Systematic review registrationhttps://inplasy.com/inplasy-2023-2-0083.

BackgroundInterleukin-6 (IL-6) is essential for maintaining intestinal epithelial homeostasis. Although cold water-immersion restraint (CWIR) stress is commonly used to induce in vivo gastric injury, it also affects intestinal epithelial permeability. Although IL-6 is increased in response to acute physiological and psychological stress, its exact effects on the pathophysiology of the intestinal epithelium in response to acute CWIR stress remain unknown.MethodsWe used IL-6 knockout (KO) mice with acute CWIR modeling to investigate the effect of IL-6 deficiency on intestinal epithelial morphology and pathological damage using histological staining assays under the acute stress. We detected jejunal epithelial apoptosis using TUNEL and standard molecular experiments.ResultsCWIR caused intestinal epithelial damage, which was alleviated by the absence of IL-6, as evidenced by morphological changes and goblet cell and intestinal permeability alteration. IL-6 KO also reduced CWIR-mediated inflammatory levels and improved stress defense. Meanwhile, IL-6 deficiency decreased the intestinal epithelial apoptosis induced by CWIR administration. This IL-6 KO-led effect depended more on mitochondrial AIF signaling rather than the traditional caspase pathway.ConclusionAs a result, we concluded that acute CWIR-induced severe intestinal damage and jejunal epithelium apoptosis could be alleviated by IL-6 deficiency, implying a protective effect of IL-6 deficiency on the intestines under acute stress. The findings shed new light on treating CWIR-induced intestinal disorders by inhibiting IL-6 signaling.

Understanding the influence of vegetation types on soil particle-size distribution (PSD) is essential to evaluate the effects of sediment control by vegetation restoration. In this work, we studied the effects of different vegetation types, including bare land, meadow, shrub and forest on soil PSD in Jiangjiagou gully, Yunnan province, China. A total of 60 soil samples were collected and analyzed for soil particle size distribution using the laser diffraction method. Fractal theory was used to calculate multifractal parameters. The volume fraction of silt particles in shrub and forest is significantly higher than that in bare land, meadow, whereas the total volume fraction of sand particles in bare land and meadow exceed that in shrub and forest. The soil particle size distribution along soil layers has no significant difference in each vegetation type. The volumetric fractal dimension is significantly higher in forest and shrub than in bare land and grassland, but there is no significant difference between forest and shrub. In addition, soil erosion resistance exhibits significant differences of forest > shrub > grassland > bare land. Multifractal parameters are highest in bare land except for multifractal spectrum values (f (αmax) and f (αmin)) and the maximum value of singularity index (αmin). All generalized dimensions spectra curves of the PSD are sigmoidal, whereas the singular spectrum function shows an asymmetric upward convex curve. Furthermore, soil erosion resistance has significant relationships with multifractal parameters. Our results suggest that multifractal parameters of the soil PSD can predict its anti-ability to erosion. This study also provides an important insight for the evaluation of soil structure improvement and the effects of erosion control by vegetation restoration in dry-hot valley areas.

Growing evidence has demonstrated that stress triggers gastrointestinal (GI) disorders. This study aimed to investigate how the acute cold water-immersion restraint (CWIR) stress affects intestinal injury and gut microbiota (GM) distribution. Male C57BL/6 mice were used to establish a CWIR animal model. Hematoxylin–eosin and periodic acid–Schiff staining were performed to assess intestinal histopathological changes. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and immunofluorescence staining were used to evaluate the expression of inflammatory cytokines and immune cell infiltration in the intestinal tissues. The gut permeability and intestinal occludin protein expression were determined through fluorescein isothiocyanate-dextran detection and western blot, respectively. GM profiles were analyzed via high-throughput sequencing of the fecal bacterial 16S rRNA genes. Results showed that CWIR induced more severe intestinal mucosal injury compared to the control, leading to a significant increase in tumor necrosis factor-α expression, but no infiltration of neutrophil and T cells. CWIR also resulted in GI disruption and increased the permeability of the intestinal mucosa. GM profiles showed that CWIR reduced GM diversity of mice compared with the control group. Specifically, aerobic and gram-negative bacteria significantly increased after CWIR, which was associated with the severity of gut injury under stress. Therefore, acute CWIR leads to severe intestinal damage with inflammation and disrupts the GM homeostasis, contributing to decreased GM diversity. Our findings provide the theoretical basis for the further treatment of intestinal disorders induced by CWIR.

BackgroundsBreast cancer is a heterogeneous disease without clear pathogenesis and effective primary prevention. The “anti-cancer” effects of several trace elements have received increasing attention in recent years. The main purpose of current study is to explore the differences of three potential “anti-cancer” trace elements selenium (Se), molybdenum (Mo), and strontium (Sr) between patients with malignant breast tumors and healthy controls.MethodsWe conducted a case–control study in 45 patients with malignant breast tumors as cases and 95 healthy volunteers as controls from Peking University Third Hospital, Beijing, China. The serum concentrations of trace elements were evaluated by using inductively coupled plasma mass spectrometry (ICP-MS).ResultsThe cases may have a lower Se levels when compared with controls (cases: 106.22 ng/ml, SD: 20.95 ng/ml; controls: 117.02 ng/ml, IQR: 22.79 ng/ml, p = 0.014). High levels of Se were a protective factor from breast cancer after adjusting the potential confounders of age, BMI, smoking, drinking, and menopause status (OR = 0.395, 95% CI, 0.178, 0.877, p = 0.023). The levels of Sr were lower in cases with high histologic grade when compared to low histologic grade (low histologic grade: 49.83 ng/ml, IQR: 41.35–62.60 ng/ml; high histologic grade: 40.19 ng/ml, IQR: 39.24–47.16 ng/ml, p < 0.05).ConclusionsOur findings herein supported that Se has protective effects to avoid malignant breast tumors and Sr has protective effects to avoid poorly differentiated malignant breast tumors. Exploring “anti-cancer” related trace elements and their associations with breast cancer will assist for the early prevention and intervention for the disease.

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.

BackgroundOsteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.MethodsHuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.ResultsKnockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.