Search

Abstract R-loops are three-stranded nucleic acid structures composed of an RNA–DNA hybrid and a displaced DNA strand. They are widespread and play crucial roles in regulating gene expression, DNA replication, and DNA and histone modifications. However, their regulatory mechanisms remain unclear. As R-loop detection technology advances, changes in R-loop levels have been observed in cancer models, often associated with transcription-replication conflicts and genomic instability. N6-methyladenosine (m6A) is an RNA epigenetic modification that regulates gene expression by affecting RNA localization, splicing, translation, and degradation. Upon reviewing the literature, we found that R-loops with m6A modifications are implicated in tumor development and progression. This article summarizes the molecular mechanisms and detection methods of R-loops and m6A modifications in gene regulation, and reviews recent research on m6A-modified R-loops in oncology. Our goal is to provide new insights into the origins of genomic instability in cancer and potential strategies for targeted therapy.

Abstract Background Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. Graphical Abstract

Abstract Background Currently, most elderly chronic heart failure (CHF) patients go home for rehabilitation after certain treatment in hospitals. However, the results of their rehabilitation at home are not satisfactory. According to studies, dyadic treatments can increase the efficiency of home rehabilitation, enhance both partners' quality of life, lessen the caregiver's load of care, and alleviate the strain of medical resources. Thus, the aim of our research is to design a study protocol that included elderly CHF patients and their informal caregivers as an intervention unit and to explore the impact of the protocol on their health and physical outcomes. Methods This is a prospective randomized controlled trial conducted in a triple-A hospital. In total, 80 elderly CHF patients and informal caregivers (80 dyads) will be recruited with informed consent. Based on the randomized numbers, they are divided into a control group (40 dyads) and an intervention group (40 dyads), subjects in the control group will receive usual care, and subjects in the intervention group will receive a home-based disease management program based on the Theory of Dyadic Illness Management on the basis of the control group. The duration of the intervention is 3 months, and the follow-up is 6 months. Data is collected at enrolment, 3 months after the intervention, and 3 months after the end of the intervention. The primary outcome is patients’ quality of life and readmission. Secondary outcomes include patients’ self-management behaviors, anxiety, and depression and caregivers’ quality of life and care burden. Discussion This study focuses on whether this home-based disease management program can improve the quality of life of elderly patients with CHF, reduce the readmission rate, enhance their self-management capacity, reduce negative emotions, and reduce the burden of informal caregivers. It can provide a new perspective on home management and cardiac rehabilitation of heart failure disease in the elderly, as well as alleviate problems such as the burden of healthcare resources. Trial registration Chinese Clinical Trials Registry ChiCRT2300068026. Registered on 3 February 2023, manuscript Version: 1.0, https://www.chictr.org.cn/ .

Abstract Background Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. Results Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. Conclusions This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules. Graphical Abstract

Abstract Background Ambient particulate matter (PM) exposure is recognized as a risk factor for cardiovascular disease (CVD). However, the extent to which PM exposure is associated with CVD via triglyceride glucose (TyG)-related indicators remains unknown. This study examines the relationship between long-term PM exposure and CVD events, further assessing whether TyG-related indicators mediate this association. Methods This cohort study involved 7,532 individuals aged at least 45 years who were not diagnosed with CVD in 2011 from the China Longitudinal Study of Health and Retirement (CHARLS) and were followed up for the occurrence of CVD until 2020. The annual PM concentration data at the city level, with aerodynamic diameters ≤ 1 μm (PM1), ≤ 2.5 μm (PM2.5), and ≤ 10 μm (PM10), were obtained from the ChinaHighAirPollutants (CHAP). The average concentration of PM in the 3 years before the baseline survey in 2011 was defined as the long-term exposure level of the individual. The relationship between PM exposure and CVD incidence was examined via Cox proportional hazards models, with a focus on probing the role of TyG-related indicators through mediation analysis. Results A total of 1,865 individuals with CVD were diagnosed over the span of a 7.4-year follow-up period. The 3-year average concentrations before baseline were 31.29 µg/m³ for PM1, 56.03 µg/m³ for PM2.5, and 95.73 µg/m³ for PM10. In fully adjusted model, the Cox proportional hazards models revealed that an increase of 10 µg/m³ in the PM1, PM2.5, and PM10 exposure concentrations corresponded to elevated CVD risk, with HRs (95% CI) of 1.135 (1.078–1.195), 1.092 (1.062–1.123), and 1.075 (1.059–1.090), respectively. Mediation analyses further suggested that the correlation between PM exposure and CVD could be partly mediated via TyG-BMI, TyG-WC, and TyG-WHtR, with mediation proportions varying from 5.54 to 15.30%. Conclusion A significant correlation was observed between long-term PM exposure and increased CVD risk, with TyG-related indicators, such as TyG-BMI, TyG-WC, and TyG-WHtR, partially mediating this relationship.

Super 13Cr, as an economy stainless steel (SS) for oil country tubular goods, needs stable corrosion resistance in high-pressure and high-temperature (HPHT) downhole medium. Severe plastic deformation (SPD) are the surface modification technology to improve mechanical properties, fatigue behavior and corrosion resistance of metals, and shot peening (SP) has been the most widely used SPD process. However, there are quite limited studies about the microsutructure evolution, residual stress, and high-temperature corrosion behavior of SP-treated martensitic SS. In this study, super 13Cr martensitic SS was treated by SP with various air pressures and nozzle speeds. The surface characteristics and high-temperature corrosion behaviour in 3.17 mol/L K2HPO4 solution were investigated through finite element model analysis, characterization of residual stress and microstructure, as well as electrochemical and stress corrosion cracking (SCC) tests at 160 °C and 10 MPa. The results showed that SP-treated super 13Cr could generate high-level compressive residual stress and SPD microstucture, including nano-sized equiaxed grains, gradient lamellar structure and fragmented carbides. Increasing air pressure contributed to achieve uniform nanocrystalline, but tended to generate high dislocation density and surface defects. The improving effect of SP treatment at low air pressure of 0.15 MPa on passivation ability was limited, and high air pressure adversely impacted corrosion resistance. SP-treated specimens showed high SCC susceptibility, due to the introduction of more surface defects, high angle grain boundaries, and dislocations.

Abstract Background Plants that contain brewing microorganisms are used in traditional fermentation starters, which are an essential part of local diet, nutrition, life, and health. Regionally, the plant species used and the microorganisms included in traditional fermentation starters are diverse, endowing local fermented drinks with different flavors and health benefits. However, related traditional knowledge has been scarcely documented or revealed. Methods An ethnobotanical survey was conducted in five towns of Nayong County in northwestern Guizhou, China. Snowball sampling, semi-structured interviews, free lists, and participatory observation were used to collect information on Jiuqu Plants (JPs) and jiuqu-making techniques. The PacBio platform was used to study the microbial community structure and diversity in the Chuanqing people’s jiuqu. Results In total, 225 informants were interviewed, including 116 who provided plants and technological processes for making Chinese baijiu jiuqu (CBJ) and 139 who provided information about making fermented glutinous rice jiuqu (FGRJ). This study found that older people have more abundant knowledge about CBJ plants. Poaceae was found to be the dominant family used in making CBJ and FGRJ (7 species each). Compared to individual plant parts, the whole plant is most commonly used in two kinds of jiuqu (19.5% in CBJ and 22.6% in FGRJ). The Chuanqing people’s jiuqu is used to treat dietary stagnation and indigestion. The highest relative frequency of citation of the CBJ plant was Ficus tikoua Bureau, and the counterpart of the FGRJ plant was Buddleja macrostachya Benth. The dominant bacterial species in jiuqu were Gluconobacter japonicus (YQ1, YQ4) and Pediococcus pentosaceus (YQ2, YQ3), and the dominant fungal species was Rhizopus oryzae. Conclusion For the first time, this study documents the unique traditional jiuqu knowledge and reveals the microbial mystery behind the FGRJ of the Chuanqing people. Therefore, this study encourages the use of online social media platforms in order to spread Jiuqu culture, the use of the new media wave in order to create multimedia databases, and also suggests that local communities should develop preservation intervention programs, in addition to nurturing the inheritors in order to prevent the disappearance of traditional Jiuqu knowledge. This research contributes to the conservation and demystification of the traditional jiuqu knowledge of the Chuanqing people and lays the foundation for further research on its microbiology, nutrition, and metabolomics.

Parameter identification involves the estimation of undisclosed parameters within a system based on observed data and mathematical models. In this investigation, we employ DAISY to meticulously examine the structural identifiability of parameters of a within-host SARS-CoV-2 epidemic model, taking into account an array of observable datasets. Furthermore, Monte Carlo simulations are performed to offer a comprehensive practical analysis of model parameters. Lastly, sensitivity analysis is employed to ascertain that decreasing the replication rate of the SARS-CoV-2 virus and curbing the infectious period are the most efficacious measures in alleviating the dissemination of COVID-19 amongst hosts.

Abstract Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.

Abstract Background Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press–strain loop (LV-PSL). Methods Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL

Objective To investigate the genotypes of human papillomavirus (HPV) infection in male patients with condyloma acuminatum (CA) and to develop a model for predicting recurrence risk. Methods Wart samples were collected from 724 CA patients at Jiaozhou Branch of Shanghai East Hospital, Tongji University from January 2021 to June 2023. Human papillomavirus DNA was extracted and genomic DNA was genotyped. Multivariate logistic regression analysis was used to analyze the risk factors for recurrence within 6 months after being cured with physiotherapy, and a prediction model for recurrence risk was developed. Receiver operating characteristic (ROC) curves was used to verify the prediction value of the prediction model. Results Among 724 CA patients, the main genotypes were HPV 6, 11, 16, and 42. Multivariate logistic regression analysis showed that a disease course of ≥ 6 months, high-risk HPV infection, multiple HPV infections, and the number of warts ≥ 5 were independent risk factors for recurrence (P13.00, the sensitivity and specificity were 71.39% and 83.01%, respectively, and the area under the curve (AUC) was 0.863. Conclusions The main genotypes of HPV infection are HPV 6, 11, 16, and 42 in male CA patients. The prediction model for recurrence risk factors has high predictive value for predicting recurrence of CA.

Abstract Alternative polyadenylation (APA) is a crucial mechanism for regulating gene expression during pre-mRNA 3′ processing. Pre-mRNA 3′ end processing factors is the main factor involved in this process. However, pre-mRNA 3′ end processing factors in different cancer expression profiles and the relationship between pre-mRNA 3′ end processing factors and tumor microenvironment and the prognosis of the same patient is still unclear. In this study, we conducted a comprehensive exploration of the core pre-mRNA 3′ end processing factors across various cancer types by utilizing common cancer database, and revealing a robust correlation between the expression of these core factors and tumor characteristics. Leveraging advanced bioinformatics databases, we evaluated the expression levels and prognostic relevance of pre-mRNA 3′ end processing factors across pan-cancer tissues. Our extensive pan-cancer analysis revealed unique expression patterns of pre-mRNA 3′ end processing factors in both tumor and adjacent non-tumorous tissues. Notably, we found a significant correlation between the expression levels of pre-mRNA 3′ end processing factors and patient prognosis. Furthermore, we identified strong associations between pre-mRNA 3′ end processing factors expression and various factors, such as stromal, immune, RNA stemness, and DNA stemness scores across pan-cancer tissues. Our data also highlighted a link between the expression of pre-mRNA 3′ end processing factors and sensitivity to specific drugs, including pyrazoloacndine, amonaflide, and chelerythrinede, among others. We found four key pre-mRNA 3′ end processing factors that play a crucial role in mRNA preprocessing. Our study illuminates the potential promotion and inhibition role of pre-mRNA 3′ end processing regulators in the progression of cancer, CPSF2, CPSF3, CSTF2, SYMPK offering valuable insights for future research investigations on these regulators as diagnostic markers and therapeutic targets across pan-cancer.

Abstract To understand the ecology of species and promote biotechnology through beneficial strain selection for improving starch yield in maize wet-milling steeping, bacterial diversity and community structure during the counter-current steeping process in a commercial steeping system were characterized and investigated. The microbial diversity in the steeping liquor, which consisted of 16 phyla, 131 families, and 290 genera, was more abundant compared to those present on the surface of unsteeped maize. As the counter-current steeping progressed, exposing newer maize to the older steepwater, Lactobacillus dominated, replacing Rahnella, Pseudomonas, Pantoea, and Serratia. The thermophilic and acidophilic microbial consortia were enriched through adaptive evolution engineering and employed to improve starch yield. Several steeping strategies were evaluated, including water alone, SO2 alone, mono-culture of B. coagulans, microbial consortia, and a combination of consortium and SO2. Combining the microbial consortium with SO2 significantly increased the starch yield to, about 66.4 ± 0.5%, a 22% and 46% increase over SO2 alone and the consortium alone, respectively. Scanning electron microscope (SEM) of steeped maize structure indicated that the combination of consortium and SO2 disrupted the protein matrix and widened gaps between starch granules in maize endosperm. This released proteins into the steepwater and left starch granules in the aleurone layer. The steeping strategy of using thermophilic and acidophilic microbial consortium as additives shows potential application as an environmentally friendly alternative to conventional maize steeping procedures.

Abstract Background The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. Methods This hospital-based, cross-sectional study was conducted at the Third People’s Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. Results The study included participants primarily between the ages of 20–40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. Conclusion Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

Understanding the precise mechanism of BMSC (bone marrow mesenchymal stem cell) osteogenesis is critical for metabolic bone diseases and bone reconstruction. The histone-lysine N-methyltransferase 2D (KMT2D) acts as an important methyltransferase related with congenital skeletal disorders, yet the function of KMT2D in osteogenesis was unclear. Here we found that KMT2D expression was decreased in BMSCs collected from ovariectomized mice. Moreover, during human BMSC differentiation under mineralization induction, the mRNA level of KMT2D was gradually elevated. After KMT2D knockdown, the in vitro osteogenic differentiation of BMSCs was inhibited, while the in vivo bone formation potential of BMSCs was attenuated. Further, in BMSCs, KMT2D knockdown reduced the level of phosphorylated protein kinase B (p-AKT). SC-79, a common activator of AKT signaling, reversed the suppressing influence of KMT2D knockdown on BMSCs differentiation towards osteoblast. These results indicate that the KMT2D-AKT pathway plays an essential role in the osteogenesis process of human BMSCs (hBMSCs), which might provide new avenues for the molecular medicine of bone diseases and regeneration.

Abstract The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Abstract Focusing on the anthropogenic aerosols effects on the East Asian Summer Monsoon (EASM) progression, we found that aerosols delay the northward progression of EASM by one pentad in the south of the middle-lower reaches of the Yangtze River (PD1: pentads 25-35) and the North-Northeast China (PD3: pentads 38-42). However, aerosols have minimal impact on the seasonal march of EASM over the Yangtze-Huai River basin (PD2: pentads 36-37). In PD1 and PD3, aerosols reduce sea-land temperature differences. Also, a southward shift in the westerly jet causing lower-level north winds, which weakens the EASM in PD3. The delayed EASM progress shows its weakness in PD1 and PD3. While in PD2, EASM intensity weakens without affecting its northward progression. Aerosols, though affecting the position and intensity of Western Pacific Subtropical High, minimally influence its northward movement speed, hence no effect on the seasonal march of EASM in PD2.

The complete intestinal structure is important to ensure the rapid and h ealthy growth of fish. However, the feed composition, aquaculture water environment, intestinal microbial population, and other factors may affect the intestinal health of fish. Intestinal health problems caused by feed ingredients are mainly due to the antinutrient factors contained in raw materials. Antinutritional factors contained in high-level soybean meal can cause oxidative damage to the intestine, thus, inducing soybean meal-induced enteritis (SBMIE), which leads to a decreased appetite and the slow growth of fish. Alleviating the damage of soybean meal to the fish intestinal tract and improving intestinal health through nutrition are essential methods for ensuring the sustainable development of the feed industry, which has significant ecological and economic significance.As a functional amino acid, arginine is a precursor to the synthesis of bioactive substances, such as urea, glutamic acid, creatine, proline, polyamine, and nitric oxide. Arginine modulates metabolic regulation, including growth, immunity, intestinal barrier, and endocrine regulation. It plays a vital role in the immune regulation, maintenance, and protection of the intestinal mucosal structure and function. It has been reported that arginine is beneficial for repairing intestinal mucosal injury in poultry and aquatic animals. In this study, the carnivorous marine economic fish Sebastes schlegelii (54.97±0.12) g were used to investigate the repair effect and mechanism of arginine on SBMIE. This study aimed to provide a scientific basis for the application of arginine for maintaining the intestinal health of fish and provide a reference for the application of plant protein to the compound feed of the carnivorous economic fish S. schlegelii.The purpose of this study was to investigate the repairing effects of arginine on the growth performance, arginine metabolism, intestinal structure, antioxidant performance, relative expression levels of intestinal tight junction protein genes (occludin, clnd15, and zo-1), and inflammatory factor-related genes (il-1β, il-8, il-15, and tlr8) and anti-inflammatory factor-related gene (il-12b) of S. schlegelii with SBMIE. S. schlegelii were fed high-level soybean meal (40%) for 28 days to induce SBMIE. SBMIE-S. schlegelii weighing (54.97±0.12) g were used as the study animals. Four isonitrogen and isoenergetic experimental feeds were formulated. The basic formula was supplemented with 30% soybean meal, arginine 0 supplementation as the control group (D0), and 1%, 2%, and 3% arginine supplementation as the treatment groups, named D1, D2, and D3, respectively. Each diet group had three replicates, and each replicate consisted of 40 fish. The fish were randomly placed in 12 homemade cages (60 cm × 60 cm × 90 cm). The experiment lasted for 6 weeks. The experimental fish were fed twice a day (08:00 and 17:00), with the initial feeding amount being 1% of the body weight, and the feeding amount being adjusted according to the feeding situation. During the experiment, the bottom of the cages was cleaned, and the water was changed every day to maintain the water temperature at 18~22 ℃, the dissolved oxygen at > 6 mg/L, the pH at 7.6~8.2, the ammonia nitrogen content at < 0.05 mg/L, and the nitrite nitrogen content at < 0.05 mg/L. The light cycle was the natural cycle. The results showed that the weight gain rate of the fish in the D2 and D3 groups was significantly higher than that in D0 group (P < 0.05). The hepatosomatic and viscerosomatic indexes of the fish in the arginine treatment groups were significantly lower than those in the D0 group, and the condition factor was significantly higher than that in the D0 group (P < 0.05). There was no significant effect on the survival rate (P > 0.05). Diamine oxidase (DAO) activity, NO content, and iNOS activity values in the serum of the treatment groups were significantly lower than those in the D0 group (P < 0.05). The serum T-NOS activity in the D2 and D3 groups was significantly lower than that in the D0 group (P < 0.05). The duplicature height in the treatment groups was significantly higher than that in the D0 group, while no significant difference was found in the duplicature number and muscle thickness (P > 0.05). In group D0, the intestinal mucosa lamina propria widened, and the number of goblet cells increased, while in groups supplemented with arginine, the intestinal mucosa was intact, and the problems mentioned above improved significantly. Intestinal total antioxidant capacity (T-AOC) in arginine supplementation groups was significantly increased, and the highest value was found in group D2 (P < 0.05). The malondialdehyde content in groups D2 and D3 was decreased significantly compared to that in the D0 group (P < 0.05). The relative expression of occludin mRNA in each treatment group was significantly upregulated compared to that in the D0 group (P < 0.05). The relative expression level of clnd15 mRNA in the D2 group was significantly higher than that in the D0 and D1 groups (P < 0.05). The relative expression level of zo-1 mRNA in group D1 was significantly higher than that in the other groups (P < 0.05). The relative expression levels of IL-1β, IL-15, and TLR8 mRNA were downregulated in all treatment groups, while the relative expression of IL-12b mRNA was upregulated (P < 0.05). No significant differences were found in IL-8 mRNA relative expression (P > 0.05). In conclusion, under the conditions of this experiment, the growth and antioxidant performances of S. schlegelii with SBMIE were significantly increased, arginine metabolism and the intestinal structure were improved significantly, and the relative expression of intestinal tight junction protein and anti-inflammatory factor-related genes was upregulated, while that of inflammatory factor-related genes was downregulated, with arginine supplementation in a high-level soybean meal diet. Arginine (2% best) was effective in repairing SBMIE of S. schlegelii. The results of this study provide a theoretical basis for the mechanism of repairing SBMIE with arginine.

Abstract This study investigates the longitudinal dynamic changes in immune cells in COVID-19 patients over an extended period after recovery, as well as the interplay between immune cells and antibodies. Leveraging single-cell mass spectrometry, we selected six COVID-19 patients and four healthy controls, dissecting the evolving landscape within six months post-viral RNA clearance, alongside the levels of anti-spike protein antibodies. The T cell immunophenotype ascertained via single-cell mass spectrometry underwent validation through flow cytometry in 37 samples. Our findings illuminate that CD8 + T cells, gamma-delta (gd) T cells, and NK cells witnessed an increase, in contrast to the reduction observed in monocytes, B cells, and double-negative T (DNT) cells over time. The proportion of monocytes remained significantly elevated in COVID-19 patients compared to controls even after six-month. Subpopulation-wise, an upsurge manifested within various T effector memory subsets, CD45RA + T effector memory, gdT, and NK cells, whereas declines marked the populations of DNT, naive and memory B cells, and classical as well as non-classical monocytes. Noteworthy associations surfaced between DNT, gdT, CD4 + T, NK cells, and the anti-S antibody titer. This study reveals the changes in peripheral blood mononuclear cells of COVID-19 patients within 6 months after viral RNA clearance and sheds light on the interactions between immune cells and antibodies. The findings from this research contribute to a better understanding of immune transformations during the recovery from COVID-19 and offer guidance for protective measures against reinfection in the context of viral variants.

Abstract LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

In this paper, the active parts of sea cucumber (Apostichopus japonicus) with high antihypertensive activity were screened and the preparation process of active peptides was optimized. Different parts (body wall, intestine, and ovum) of A. japonicus were hydrolyzed by enzymolysis, and the ACE inhibition rate was used as an indicator to screen the optimal protease. The optimal active site for inhibition was selected by comparative screening of the half maximal inhibitory concentration (IC50) determination of ACE inhibitory rate of each lysate. Single factor and response surface tests were used to determine the optimum enzymatic hydrolysis conditions of the active peptides. The relative molecular weight of the protease hydrolysates was determined to determine its distribution range. The ACE inhibition activity of different components was analyzed after separation by ultrafiltration membrane. Search results, alkaline protease was selected as the optimal hydrolytic enzyme, and the IC50 values of ACE inhibition of each protease lysate from body wall, intestine and ovum were 1.11, 4.02, 0.65 mg/mL, respectively, so that A. japonicus ovum had a better ACE inhibition effect and were the optimal active site for inhibition. Its optimal preparation process parameters for enzymatic hydrolysis were as follows: 5 h enzymatic hydrolysis time, 3.5 U/mg enzyme added, 65.26 °C enzymatic hydrolysis temperature, 3.51% substrate concentration, pH9.02 enzymatic hydrolysis, and ACE inhibition rate of A. japonicusr ovum was 80.65%±0.52% under these conditions, which was close to the predicted value. The molecular weight of proteolytic products was concentrated under 3000 Da, accounting for 98.37% of the total content, of which 1000~3000 Da accounted for 9.50%, and less than 1000 Da accounted for 88.87%. The ACE inhibitory activity of oligopeptide components (IC50=0.30 mg/mL) isolated by ultrafiltration membrane was significantly higher than that of hydrolysates and trapped liquid components after process optimization. The results of this study would provide a theoretical basis for high-quality utilization of the by-products of A. japonicus, which could be used as high-quality resources for the isolation and purification of antihypertensive peptides.

Human milk oligosaccharides (HMOs) are key components of breast milk, playing a vital role in fostering the healthy development of infants and young children. Among the main HMOs components, 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL) exhibit considerable benefits in terms of inhibiting pathogenic infections, regulating gut microbiota, and enhancing immunity. In recent years, the synthesis of 2′-FL and 3-FL has emerged as a prominent area of research in the field. Despite the potential advantages of chemical or enzymatic synthesis of 2′-FL and 3-FL, these methods are hindered by their inherent limitations, including intricate reaction procedures, high costs, and poor yield, which are not conducive to meeting the demand of the market. Therefore, more efficient microbial methods have been developed and applied in the commercial production of 2′-FL and 3-FL. This article systematically outlines the methods for preparing both 2′-FL and 3-FL, thoroughly expounds upon the engineering strategies for microbial synthesis of 2′-FL and 3-FL, and provides a compelling framework for further microbial production exploration of 2′-FL and 3-FL.

Abstract Background Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. Results A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). Conclusions In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

The addition of non-templated nucleotides at the 3’ terminus of RNA is a pervasive and evolutionarily conserved posttranscriptional modification in eukaryotes. Apart from canonical poly(A) polymerases (PAPs), which are responsible for catalyzing polyadenylation of messenger RNAs in the nucleus, a distinct group of non-canonical PAPs (ncPAPs), also known as nucleotidyl transferase proteins (NTPs), mediate the addition of uridine and adenosine or of more intricate combinations of nucleotides. Among these, HEN1 SUPPRESSOR 1 (HESO1) and UTP: RNA URIDYLYLTRANSFERASE (URT1) are the two most extensively studied NTPs responsible for the addition of uridine to the 3’ ends of RNAs (RNA uridylation). Recent discoveries have improved our understanding of the functions and mechanisms of uridylation mediated by HESO1 and URT1 in RNA metabolism. Furthermore, more NTPs have been identified to function in the 3’ tailing of RNA and not solely through uridylation. Accumulating evidence indicates that RNA tailing plays important roles in plant growth and development, stress responses, and disease resistance. In this review, we examined the latest developments in RNA tailing by NTPs, with a focus on RNA uridylation and metabolism in plants. We also discussed the essential aspects for future research in this field.

Metastasis is the main cause of death in cancer patients, the lung is one of the most common metastatic organs of malignant solid tumors. Before tumor cells metastasize to the lungs, they interact with immunosuppressive cells, alveolar epithelial cells, and lung fibroblasts to form a pre-metastatic niche. The pre-metastatic niche is a key factor leading to tumor cell metastasis to the lungs. Research has found that traditional Chinese medicine and its components can inhibit the formation of pre-metastatic niche. Therefore, this article reviewed the research progress on the formation of lung pre-metastatic niche and the intervention of traditional Chinese medicine in pulmonary PMN, in order to provide new Chinese medicine prescriptions and research ideas for further clinical prevention and treatment of tumor metastasis to the lung.

Objective: The prognostic implication of phosphorus level in patients with coronary artery disease (CAD) remains controversial. We aimed to conduct a meta-analysis to evaluate the prognostic role of blood phosphorus level in CAD patients. Methods: We searched the PubMed, Web of Science, Scopus, and Embase databases until December 28, 2023, to identify prospective or retrospective longitudinal observational studies that examined the prognostic value of blood phosphorus level in CAD patients. Outcome measures included all-cause or cardiovascular mortality, heart failure, stroke, and major adverse cardiac events (MACEs). The prognostic value of blood phosphorus level was expressed by pooling the fully adjusted hazard ratios (HR) with 95 % confidence intervals (CI) for the hypophosphatemia or hyperphosphatemia compared to the reference normal phosphorus level. Results: Six studies involving 19,553 CAD patients were included. Meta-analysis showed that the hyperphosphatemia was significantly associated with higher risk of all-cause mortality (HR 1.39; 95 % CI 1.20–1.61), cardiovascular mortality (HR 1.37; 95 % CI 1.22–1.53), heart failure (HR 1.64; 95 % CI 1.44–1.87), and MACEs (HR 1.39; 95 % CI 1.03–1.88) but not stroke (HR 1.23; 95 % CI 0.79–1.92). However, non-significant association was found between hypophosphatemia and all-cause mortality (HR 1.21; 95 % CI 0.98–1.51), cardiovascular mortality (HR 1.07; 95 % CI 0.78–1.45), heart failure (HR 0.87; 95 % CI 0.72–1.05), stroke (HR 1.12; 95 % CI 0.76–1.67), and MACEs (HR 1.16; 95 % CI 0.99–1.36). Conclusions: Hyperphosphatemia, but not hypophosphatemia independently predicts all-cause mortality, cardiovascular mortality, heart failure, and MACEs in CAD patients.

Background: Few studies have compared the performances of those reported miRNAs as biomarkers for heart failure with reduced EF (HFrEF) in a population at high risk. The purpose of this study is to investigate comprehensively the performance of those miRNAs as biomarkers for HFrEF. Methods: By using bioinformatics methods, we also examined these miRNAs' target genes and possible signal transduction pathways. We collected serum samples from patients with HFrEF at Zhongshan Hospital. Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of those miRNAs as biomarkers for HFrEF. miRWALK2.0, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to predict the target genes and pathways of selected miRNAs. Results: The study included 48 participants, of whom 30 had HFrEF and 18 had hypertension with normal left ventricular ejection fraction (LVEF). MiR-378, miR-195-5p were significantly decreased meanwhile ten miRNAs were remarkably elevated (miR-21-3p, miR-21-5p, miR-106-5p, miR-23a-3p, miR-208a-3p, miR-1-3p, miR-126-5p, miR-133a-3p, miR-133b, miR-223-3p) in the serum of the HFrEF group. Conclusion: The combination of miR 133a-3p, miR 378, miR 1-3p, miR 106b-5p, and miR 133b has excellent diagnostic performance for HFrEF, and there is a throng of mechanisms and pathways by which regulation of these miRNAs may affect the risk of HFrEF.

A feeding trial was conducted to evaluate growth, body composition, serum biochemistry, digestion and metabolism, and oxidation resistence of S. schlegelii fed 9 diets in a 3×3 factorial design (protein levels: 44 %, 48 %, 52 %; lipid levels: 6 %, 10 %, 14 %), to optimize protein and lipid levels for practical feed formula. Rockfish (114.25 g) were stocked into 27 cages in an offshore system and fed test diets to satiation twice daily for 8 weeks. Growth increased but feed conversion rate decreased with dietary protein increasing. Increasing dietary protein to >48 % led to reduced feeding intake but increased protein efficiency ratio. Lipid efficiency ratio increased with dietary protein increasing but decreased with dietary lipid increasing. Hepatosomatic index decreased coupling with the increases in condition factor and liver lipid content as dietary lipid increased to 14 %. Intraperitoneal fat ratio increased with dietary lipid increasing. Increasing dietary protein to > 48 % significantly elevated serum total protein and glucose concentrations, hepatic glycogen synthase activity. High-protein (52 %) diets elevated serum albumin and urea nitrogen concentrations, hepatic pyruvate kinase and alanine aminotransferase (ALT) activities but downregulated hepatic growth-hormone (GH) receptor. Activities of trypsin, lipase, serum superoxide dismutase and total antioxidant capacity decreased with the dietary lipid increasing. Increasing dietary lipid to > 10 % reduced serum GH concentration, and high-lipid (14 %) diets significantly enhanced serum triglyceride concentration and hepatic transaminases activities, and resulted in a visual increase of adipocytes in liver. Serum cholesterol and low-density lipoprotein decreased as dietary protein increased to 48–52 % or dietary lipid >10 %. Hepatic succinate dehydrogenase activity and serum IGF-1 significantly increased while hepatic fatty acid synthetase decreased as dietary protein increased to >48 % or dietary lipid >10 %. High-protein (52 %) diet or high-lipid (14 %) diet elevated serum malonaldehyde concentration. These findings suggested 48 % protein and 10 % lipid were the optimal in diet for subadult S. schlegelii.

Background: Cardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. Methods: We followed 364,240 participants from UK Biobank aged 40–73 years from 2006 – 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. Results: During a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction

High levels of pre-existing antibodies are a major challenge for the application of viral vectors since they can severely limit their efficacy. To identify promising candidates among adeno-associated virus (AAV) based vectors for future gene therapies for the treatment of hereditary neuromuscular disorders (NMDs), we investigated the antibody levels in sera from patients with NMDs against 18 AAV types, including 11 AAVs with wild-type capsids, 5 AAVs with peptide-modified capsids and 2 AAVs with shuffled capsids. With regard to the wild-type capsid AAVs, the lowest binding antibody levels were detected against AAV6, AAV5, AAV12 and AAV9, whereas the highest binding antibody levels were detected against AAV10, AAV8, AAV1, and AAV2. The lowest neutralizing antibody levels against wild-type AAVs were detected against AAV12, AAV5, AAV9, AAV7, AAV8 and AAV10, and the highest neutralizing antibody levels were detected against AAV13, AAV2 and AAV3. Interestingly, the influence of peptide modifications or shuffling of AAV capsids on antibody binding and AAV neutralization seemed to depend on the parental AAV. While the sex of the serum donors had no significant impact on binding or neutralizing antibody levels, we observed a trend to higher binding antibodies in older serum donors against some AAV types and a clear positive correlation of neutralizing antibody titers with the age of the serum donors. The disease status on the other hand did not have a meaningful impact on antibody levels, with no changes in AAV neutralization. Our data indicate that several wild-type or peptide-modified AAV may be good candidates for therapeutic application due to low pre-existing antibody levels, and that the age of potential recipients rather than their health status with regard to NMDs has the biggest impact on vector applicability.

Summary: Cryptorchidism, commonly known as undescended testis, affects 1%–9% of male newborns, posing infertility and testis tumor risks. Despite its prevalence, the detailed pathophysiology underlying male infertility within cryptorchidism remains unclear. Here, we profile and analyze 46,644 single-cell transcriptomes from individual testicular cells obtained from adult males diagnosed with cryptorchidism and healthy controls. Spermatogenesis compromise in cryptorchidism links primarily to spermatogonium self-renewal and differentiation dysfunctions. We illuminate the involvement of testicular somatic cells, including immune cells, thereby unveiling the activation and degranulation of mast cells in cryptorchidism. Mast cells are identified as contributors to interstitial fibrosis via transforming growth factor β1 (TGF-β1) and cathepsin G secretion. Furthermore, significantly increased levels of secretory proteins indicate mast cell activation and testicular fibrosis in the seminal plasma of individuals with cryptorchidism compared to controls. These insights serve as valuable translational references, enriching our comprehension of testicular pathogenesis and informing more precise diagnosis and targeted therapeutic strategies for cryptorchidism.

IntroductionTai Chi Chuan (TCC) is a traditional Chinese mind–body exercise widely adopted in Chinese communities and colleges. However, the mindful essence of TCC is rarely emphasized during popularization. This makes it difficult for beginners to benefit from it. The present study aimed to examine the effects of a Mindfulness-enhanced Tai Chi Chuan (MTCC) intervention, which enhances mindfulness components embedded within TCC, on mental and physical health among beginners.MethodsA randomized controlled trial was conducted with 119 healthy college students new to Tai Chi Chuan training. Participants were assigned to either the MTCC group or the TCC group. Both interventions consisted of 10 weekly 90-min training sessions, with the MTCC group emphasizing and enhancing mindfulness components. Outcome measures included mindfulness, depression, anxiety, stress, and physical fitness, assessed at baseline and post-intervention.ResultsThe results showed that the MTCC group had significantly greater improvements than the TCC group in mindfulness, anxiety, stress, and health—and skill-related physical fitness. There were no significant differences between the two groups in depression.ConclusionThe findings suggest that compared to TCC, MTCC can effectively promote individuals’ physical fitness and provide additional benefits to mental well-being. MTCC can be recommended as an accessible and beneficial intervention for beginners to improve mental health and strengthen their bodies.Clinical review registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200058175.

Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.

BackgroundThe efficiency of systemic immune-inflammation index (SII) in predicting prognosis of osteosarcoma (OSA) patients has been extensively analyzed, but no consistent findings are obtained. Therefore, this meta-analysis focused on identifying the precise prognostic value of SII for OSA.MethodsWe comprehensively searched electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 24 February, 2024. Meanwhile, the efficiency of SII in predicting prognosis of OSA was evaluated by calculating pooled hazard ratios (HRs) as well as 95% confidence intervals (CIs). Additionally, the correlation of SII with the OSA clinicopathological characteristics was analyzed based on pooled odds ratios (ORs) and 95%CIs.ResultsSix studies with 1015 cases were enrolled into this work. According to the combined data, the higher SII was markedly related to poor overall survival (OS) (HR=2.01, 95%CI=1.30-3.09, p=0.002) and Enneking stage III (OR=2.21, 95%CI=1.11-4.39, p=0.024) of patients with OSA. Nonetheless, SII was not significantly related to gender, age, pathological fracture, tumor size, tumor location, tumor differentiation, and metastasis in patients with OSA.ConclusionsIn summary, the higher SII is markedly related to poor OS and advanced Enneking stage in OSA patients.Systematic review registrationhttps://inplasy.com/inplasy-2024-7-0107/, identifier INPLASY202470107.

Abstract Novel active DNA transposons, such as Spy transposons from the PHIS superfamily, are identified through bioinformatics in this study. The native transposases cgSpy and cvSpy displayed transposition activities of approximately 85% and 35% compared to the hyperactive piggyBac transposase (hyPB). The cgSpy transposon showed unique characteristics, including a lack of overproduction inhibition and reduced efficiency for insertion sizes between 3.1 to 8.5 kb. Integration preferences of cgSpy are found in genes and regulatory regions, making it suitable for genetic manipulation. Evaluation in T‐cell engineering demonstrated that cgSpy‐mediated chimeric antigen receptor (CAR) modification is comparable to the PB system, indicating its potential utility in cell therapy. This study unveils the promising application of the active native transposase, Spy, from Colletes gigas, as a valuable tool for genetic engineering, particularly in T‐cell manipulation.

Introduction: The epididymis is important for sperm transport, maturation, and storage.Methods: The head and tail of the epididymis of 5-week-old and 10-week-old C57 BL/6J male mice were used for single-cell sequencing.Results: 10 cell types including main, basal, and narrow/clear cells are identified. Next, we performed cell subgroup analysis, functional enrichment analysis, and differentiation potential prediction on principal cells, clear cells, and basal cells. Our study indicates that the principal cells are significantly involved in sperm maturation, as well as in antiviral and anti-tumor immune responses. Clear cells are likely to play a crucial role in safeguarding sperm and maintaining epididymal pH levels. Basal cells are implicated in the regulation of inflammatory and stress responses. The composition and functions of the various cell types within the epididymis undergo significant changes before and after sexual maturity. Furthermore, pseudo-temporal analysis elucidates the protective and supportive roles of epididymal cells in sperm maturation during sexual maturation.Discussion: This study offers a theoretical framework and forecasts for the investigation of epididymal sperm maturation and epididymal immunity.

Invasion and migration are the primary factors for mortality in lung adenocarcinoma (LUAD) patients. The precise role of RNA-binding motif protein15 (RBM15)-mediated m6A modification in LUAD is not yet fully clarified. This research aims to elucidate the mechanism of RBM15 in the invasion and migration of LUAD.Western blot and dot blot assay results showed that RBM15 and methylation levels of m6A were highly expressed in LUAD tissues. Overexpression of RBM15 by lentivirus transfection increased m6A levels and promoted the invasion, migration, and proliferation of A549 and H1734 cells. Knockdown of RBM15 by lentivirus transfection had opposite effects on m6A levels, invasion, migration, and proliferation of A549 and H1734 cells. The results of nude mouse proliferation models confirmed that RBM15 knockdown inhibited in vivo tumor proliferation . Sequencing and immunoprecipitation identified RASSF8 as an interacting protein of RBM15 involved in cell invasion and migration. RBM15-mediated m6A modification inhibited RASSF8 protein levels and increased LUAD cell invasion and migration. The rescue assays demonstrated that the regulation of RBM15 on LUAD cell invasion and migration was partially rescued by RASSF8.In conclusion, RBM15-mediated m6A modification inhibits the RASSF8 protein levels and increases cell invasion and migration. Thus, targeting the RBM15-m6A-RASSF8 axis may be a promising strategy for repressing LUAD cell invasion and migration.

We report a case of the meyerson phenomenon around cavernous hemangioma. A 23-year-old male presented with a dark purplish red nodule on the back for over 20 years, and pruritic annular erythema and papules with clear boundaries around the nodule for 1 day. Dermatological examination revealed a dark purplish red nodule about 0.7 cm in diameter on the back, encircled by a 1 cm diameter erythema with papules. Dermoscopic examination showed that several small purplish red cavities with clear boundaries and irregularly distributed dotted blood vessels on the skin lesion under the red background. The histopathology showed that the lesion was covered with squamous epithelium. Large irregular lumens, and sinusoids of different sizes contained red blood cells and fibrin in the superficial and deep dermis. The sinusoids were lined with a single layer of endothelial cells. The patient was diagnosed with the meyerson phenomenon around cavernous hemangioma. After surgical resection, the eczema-like dermatitis subsided. But hemangioma reoccurred without discomfort after more than 1 month. The patient is in follow-up.

Global biodiversity loss is one of the most serious environmental crises of the 20th and 21st centuries. Fish diversity, an important component of biodiversity, is also in decline. The conservation of fish diversity is therefore essential for ecosystem management and the sustainable use of resources. Most current aquatic biodiversity surveys rely on conventional methods. The emergence and application of environmental DNA (eDNA) technology has triggered unprecedented innovations in aquatic organism investigation and monitoring. eDNA metabarcoding refers to the selection of appropriate universal primers for different target taxa and the identification of multiple target species in environmental samples via PCR amplification combined with high-throughput sequencing. The Zhoushan Archipelago, located in the northeastern waters of Zhejiang Province, consists of 2 085 islands with a total area of 22 216 square kilometers. Located at the confluence of the Yangtze River, the Qiantang River, the Yongjiang River, and the Taiwan Warm Current, the Zhoushan Archipelago forms a unique and complex hydrological environment, which provides a rich source of nutrients and a suitable habitat for fish. In recent years, the large-scale exploitation of marine resources and marine pollution have led to a serious loss of fish diversity near the Zhoushan Archipelago. To restore fish diversity, conservation efforts have been implemented by the government and researchers, including stricter fishing bans and ecological fish stock enhancement and release. However, the lack of reliable tools to understand the species and assess biodiversity is the most critical issue in conservation efforts. Trawl sampling and morphological identification are the primary fish diversity assessment methods. However, these conventional methods are often inefficient, time-consuming, selective, and destructive. The extensive rocky reefs in the Zhoushan Archipelago make it difficult to use conventional fishery resource survey methods efficiently. Therefore, simple and accurate methods for species diversity monitoring are needed. In this study, Xixuan Island, an offshore island in Zhoushan, was taken as a reference. Four different sampling stations were designed, and a total of 12 water samples were collected in February, May, and November 2019. The species composition and diversity characteristics of offshore fish communities around Xixuan Island were described, and the spatial and temporal differences in fish diversity were evaluated. A total of 33 fish species belonging to 12 orders, 26 families, and 32 genera were detected. Among them, Perciformes has the most abundant species, with 19 species, accounting for approximately 57.6% of all species detected. The diversity and evenness indices of the different sampling seasons were significantly different (P < 0.05), indicating that season may be one of the factors affecting the diversity of offshore fish around Xixuan Island. The results of the combined temporal and spatial analysis showed that more fish species were detected during the breeding season at sampling sites far from the main island side of Zhoushan. By comparing the results with the conventional fishery resources survey, we found a large variation in the dominant species in different seasons, which may be related to the limited sampling site numbers. Temperature and longitude may be important factors affecting the fish diversity around Xixuan Island. The result of enriching the dominant species in each season by heat trees differed significantly from those of traditional surveys, indicating that eDNA cannot completely substitute the conventional survey methods; however, it can be applied as an auxiliary method to monitor fishery resources, improve detection efficiency, and reduce interference to ecosystems. This study not only provides novel methods for the fishery resources survey in offshore Zhoushan but also provides technical support for the subsequent investigation and evaluation of fish diversity and its protection and management.

Abstract Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Abstract Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

Abstract Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Abstract Background With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA. Results There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA. Conclusions The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.

Abstract Tongue squamous cell carcinoma (TSCC) is an aggressive oral cancer with a high incidence of metastasis and poor prognosis. We aim to identify and verify potential biomarkers for TSCC using bioinformatics analysis. To begin with, we examined clinical and RNA expression information of individuals with TSCC from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional analysis were conducted. Multiple machine-learning strategies were next employed to screen and determine the hub gene, and receiver operating characteristic (ROC) analysis was used to assess diagnostic value. Semaphorin3C (SEMA3C) was identified as a critical biomarker, presenting high diagnostic accuracy for TSCC. In the validation cohorts, SEMA3C exhibited high expression levels in TSCC. The high expression of SEMA3C was a poor prognostic factor in TSCC by the Kaplan–Meier curve. Based on the Gene Ontology (GO) analysis, SEMA3C was mapped in terms related to cell adhesion, positive regulation of JAK-STAT, positive regulation of stem cell maintenance, and positive regulation of NF-κB activity. Single-cell RNA sequencing (ScRNA-seq) analysis showed cells expressing SEMA3C were predominantly tumor cells. Then, we further verified that SEMA3C had high expression in TSCC clinical samples. In addition, the knockdown of SEMA3C suppressed the proliferation, migration, and invasion of TSCC cells in vitro. This study is the first to report the involvement of SEMA3C in TSCC, suggesting that upregulated SEMA3C could be a novel and critical potential biomarker for future predictive diagnostics, prevention, prognostic assessment, and personalized medical services in TSCC.

Abstract Mitogen‐activated protein kinase‐activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti‐cancer therapies. The limitations of ATP‐competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance. Investigating MK2's kinase domain led to the identification of a unique cysteine residue, enabling the creation of targeted covalent inhibitors. Compound 11 was developed, demonstrating robust MK2 inhibition (IC50 = 2.3 nM) and high selectivity. It binds irreversibly to MK2, achieving prolonged signal suppression and reducing pathological inflammatory cytokines in macrophages. Furthermore, compound 11 or MK2 knockdown can inhibit the tumor‐promoting macrophage M2 phenotype in vitro and in vivo. In macrophage‐rich tumor model, compound 11 notably slowed growth in a dose‐dependent manner. These findings support MK2 as a promising anticancer target, especially relevant in cancers fueled by inflammation or dominated by macrophages, and provide compound 11 serving as an invaluable chemical tool for exploring MK2's functions.

ObjectiveThis study aimed to assess the clinical effectiveness and safety of electroacupuncture (EA) for the treatment of postpartum depression (PPD).MethodsWe systematically retrieved relevant randomized controlled trials (RCTs) from electronic databases, including PubMed, Cochrane Library, China National Knowledge Infrastructure, EMBASE, China Science and Technology Journal Database, Chinese Biological Medical Database, and the Wanfang database from their inception to November 2023. The outcomes measured were the Hamilton Depression Rating Scale (HAMD) scores, Edinburgh Postnatal Depression Scale (EPDS) scores, adverse events (AEs), and the total response rate. The study aimed to estimate heterogeneity, publication bias, mean difference (MD), and risk ratios (RR) with 95% confidence intervals (CIs).ResultsThis study included 12 RCTs with a total of 1364 participants (571 in the treatment group and 793 in the control group) for analysis. The results of the meta-analysis indicated that EA did not significantly reduce HAMD (MD = 1.49, 95% CI = [−0.30, 3.27], P = 0.1, I2 = 0%) and EPDS (MD = 1.12, 95% CI = [−1.62, 3.85], P = 0.42, I2 = 32%) scores compared to sham EA among patients with PPD, resulting in low heterogeneity. In terms of the total response rate, the EA group exhibited superior results compared to the placebo group (RR = 1.77, 95% CI = [1.15, 2.74], P = 0.01, I2 = 0%) and the sham EA group (RR = 1.2, 95% CI = [1.02, 4.4], P = 0.02, I2 = 0%), with statistical significance and low heterogeneity. The incidence of AEs was lower, also with low heterogeneity (RR = 0.9, 95% CI = [0.57, 1.43], P = 0.66, I2 = 12%).ConclusionThe current evidence indicates that the effectiveness and safety of EA in the treatment of PPD warrant affirmation. However, EA does not demonstrate superiority over sham EA in reducing HAMD and EPDS scores in patients with PPD. Due to the limited quantity and quality of curent research, the above conclusion should be further validated through high-quality studies to confirm the efectiveness of EA in PPD management.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=318917, identifier CRD42023318917.

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and is characterized by the accumulation of lipid peroxides to lethal levels. Ferroptosis involves multiple pathways including redox balance, iron regulation, mitochondrial function, and amino acid, lipid, and glycometabolism. Furthermore, various disease-related signaling pathways also play a role in regulating the process of iron oxidation. In recent years, with the emergence of the concept of ferroptosis and the in-depth study of its mechanisms, ferroptosis is closely associated with various biological conditions related to kidney diseases, including kidney organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanisms of ferroptosis (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, and MBOAT1/2 pathways), and the latest research progress on its involvement in kidney diseases. It summarizes research on ferroptosis in kidney diseases within the frameworks of metabolism, reactive oxygen biology, and iron biology. The article introduces key regulatory factors and mechanisms of ferroptosis in kidney diseases, as well as important concepts and major open questions in ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs can be made in understanding the regulation mechanism of ferroptosis and utilizing ferroptosis to promote treatments for kidney diseases, such as acute kidney injury(AKI), chronic kidney disease (CKD), diabetic nephropathy(DN), and renal cell carcinoma. This paves the way for a new approach to research, prevent, and treat clinical kidney diseases.

Distinct brain regions are differentially affected during the various stages of Alzheimer's disease (AD). While the hippocampus and cortex are known to play significant roles, the involvement of the cerebellum has received less attention. Understanding the changes in diverse brain regions is essential to unravel the neuropathological mechanism in early-stage AD. Our research aimed to explore and compare amyloid-β (Aβ) pathology and gene expression profiles across the hippocampus, cortex, and cerebellum in the early stages of the Amyloid Precursor Protein/Presenilin-1 (APP/PS1) mouse model. By 7 months of age, significant Aβ plaque accumulation was observed in the hippocampus and cortex of APP/PS1 mice, while no such deposits were found in the cerebellum. Gene expression analysis revealed predominant effects on immune response pathways in the hippocampus and cortex. Even in the absence of Aβ deposition, notable gene expression changes were observed in the cerebellum of APP/PS1 mice. Intriguingly, Neuronal PAS Domain protein 4 (Npas4) expression was consistently down-regulated across all brain regions, independent of Aβ plaque presence. Our findings reveal distinct transcriptomic alterations and Aβ pathology in select cerebral regions during the initial phase of AD. Notably, the diminished expression of the Npas4 across three brain regions implies that Npas4 could play a pivotal role in the early pathogenesis of AD.

ObjectivesThe application of artificial intelligence (AI) in healthcare is an important public health issue. However, few studies have investigated the perceptions and attitudes of healthcare professionals toward its applications in nursing. This study aimed to explore the knowledge, attitudes, and concerns of healthcare professionals, AI-related professionals, and others in China toward AI in nursing.MethodsWe conducted an online cross-sectional study on nursing students, nurses, other healthcare professionals, AI-related professionals, and others in China between March and April 2024. They were invited to complete a questionnaire containing 21 questions with four sections. The survey followed the principle of voluntary participation and was conducted anonymously. The participants could withdraw from the survey at any time during the study.ResultsThis study obtained 1,243 valid questionnaires. The participants came from 25 provinces and municipalities in seven regions of China. Regarding knowledge of AI in nursing, 57% of the participants knew only a little about AI, 4.7% did not know anything about AI, 64.7% knew only a little about AI in nursing, and 13.4% did not know anything about AI in nursing. For attitudes toward AI in nursing, participants were positive about AI in nursing, with more than 50% agreeing and strongly agreeing with each question on attitudes toward AI in nursing. Differences in the numbers of participants with various categories of professionals regarding knowledge and attitudes toward AI in nursing were statistically significant (p