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IntroductionThe Calligonum species is a typical shrub with assimilative branches (ABs) in arid regions in Central Asia. The nutrient distribution patterns at different reproductive stages are of great significance for further understanding the ecological adaptation and survival strategies of plants.MethodsIn the present study, a common garden experiment was employed to avoid interference by environmental heterogeneity. Furthermore, the nitrogen (N), phosphorus (P), and potassium (K) allocation characteristics in the supporting organs (mature branches), photosynthetic organs (ABs), and reproductive organs (flowers and fruits) of Calligonum caput-medusae (CC), Calligonum arborescens (CA), Calligonum rubicundum (CR), and Calligonum klementzii (CK) during the flowering, unripe fruit, and ripe fruit phases were systematically analyzed.ResultsAboveground organs were the main factors affecting the variation of N, P, and K concentrations and their stoichiometric ratios, and the reproductive stages were secondary factors affecting N, P, and the P:K ratio and species were secondary factors affecting K and the N:P and N:K ratios. Meanwhile, significant interactions were found for all three of the aforementioned factors. The N and P concentrations in the ABs of the four species were highest during the flowering phase, while the N:P ratio was lowest, which then gradually decreased and increased, respectively, during plant growth. This result supported the growth rate hypothesis, i.e., that the growth rate is highest during the early growth stage. In the growth period, the N, P, and K concentrations in each organ of the four Calligonum species followed the power law, with the allocation rates of N and P being generally higher than K. There were differences among the species as the N−P scaling exponent in the ABs of CR was only 0.256; according to the scaling exponent law, this species was the least stressed and had the strongest environmental adaptability. Overall, the adaptability of the four species could be ranked as CR > CA > CC > CK. In conclusion, there were significant differences in nutrient traits among different aboveground organs, species, and reproductive stages.DiscussionThe results of this study contribute to a deeper understanding of the nutrient allocation strategies of different Calligonum species and provide scientific evidence for the ex-situ conservation and fixation application of these species.

BackgroundMeconopsis quintuplinervia Regel (MQ) is a traditional Chinese medicine (TCM) used for clearing liver and lung heat in Tibetan medicine for over a thousand years. However, the lack of quality markers that correlate with pharmacological actions and absorption in vivo limits the safety and efficacy in its clinical application and on the drug market. Furthermore, a universal and rapid method for simultaneously determining quality markers in the MQ crude drug is still lacking.PurposeAn absorption-based metabolite approach was used to discover and identify the quality markers of MQ. An efficient method based on polarity-switching ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS) was then established to determine the quality markers.MethodsThe absorbed compounds and metabolites were first characterized using UPLC plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) after giving oral MQ extract to rats. Subsequently, the absorbed compounds and precursors of metabolites correlating with the hepatocyte protection activity were screened as quality markers. Finally, a polarity-switching UPLC-QQQ-MS/MS method was developed for the quantitative analysis of the MQ crude drug, enabling the detection of quality markers in both negative and positive ion modes in a single run. The MS2 characteristics of target compounds were investigated to select appropriate product ions.ResultsA total of 13 absorbed compounds and 30 metabolites were characterized. Among these, nine compounds, including five absorbed compounds and four precursors of metabolites intimately correlated with hepatocyte protection activity and absorption in vivo, were considered the quality markers of MQ in the current study. The quantification of quality markers was conducted using an Acquity UPLC HSS T3 (2.1 × 100 mm, 1.8 μm) column, the mobile phase consisting of acetonitrile and 0.1% formic acid solution (containing 10 mmol/L ammonium acetate). The validated UPLC-QQQ-MS/MS method was successfully applied to quantify the quality markers in the MQ crude drug.ConclusionWe defined the quality markers and established a universal and rapid method for simultaneously determining the quality markers of MQ, which will be helpful for further investigation of the quality evaluation of MQ in clinical application and the drug market.

Manganese (Mn), a plant micronutrient element, is an important component of metalloprotein involved in multiple metabolic processes, such as photosynthesis and scavenging reactive oxygen species (ROS). Its disorder (deficiency or excess) affects the Mn-dependent metabolic processes and subsequent growth and development of plants. The beneficial element of Si has a variety of applications in agricultural fields for plant adaptation to various environmental stresses, including Mn disorder. The probable mechanisms for Si alleviation of Mn toxicity in plants are summarized as follows: (1) Si alters the rhizosphere acidification, root exudates and microorganisms to decrease the bioavailability of Mn in the rhizosphere; (2) Si down-regulates Mn transporter gene and reinforces the apoplastic barriers for inhibiting the Mn uptake and translocation; and (3) Si promotes the Mn deposition onto cell wall and Mn compartmentation into vacuole. Under Mn-deficient conditions, the probable mechanisms for Si promotion of Mn absorption in some plants remain an open question. Moreover, scavenging ROS is a common mechanism for Si alleviating Mn disorder. This minireview highlights the current understanding and future perspectives of Si regulation of manganese homeostasis in plants.

BackgroundThe objective of this study was to explore the relationship between sedentary behavior and non-suicidal self-injury (NSSI), and to provide a theoretical basis for preventing and reducing the occurrence of NSSI behavior and the development of intervention measures.MethodsBetween September and December 2021, a sedentary behavior and NSSI survey was administered to 10327 Chinese adolescents aged 12–17 who had been randomly selected using the stratified cluster random sampling method. The results were analyzed using the chi-square test and logistic regression analysis to explore the relationship between sedentary behavior and NSSI in this population.ResultsThe study found an overall NSSI detection rate among the participants of 25.1%, with occasional NSSI and frequent NSSI detection rates of 11.0% and 14.1%, respectively. The NSSI detection rate is higher in girls than in boys. After controlling for related influencing factors, the NSSI detection rates among adolescents with sedentary behavior duration ≥8 hours and screen time ≥2 hours were 1.393(β= 0.332, P

BackgroundComplications and mortality rates following gastrectomy for gastric cancer have improved over recent years; however, complications such as anastomotic leakage (AL) continue to significantly impact both immediate and long-term prognoses. This study aimed to develop a machine learning model to identify preoperative and intraoperative high-risk factors and predict mortality in patients with AL after radical gastrectomy.MethodsFor this investigation, 906 patients diagnosed with gastric cancer were enrolled and evaluated, with a comprehensive set of 36 feature variables collected. We employed three distinct machine learning algorithms—extreme gradient boosting (XGBoost), random forest (RF), and k-nearest neighbor (KNN)—to develop our models. To ensure model robustness, we applied k-fold cross-validation for internal validation of the four models and subsequently validated them using independent datasets.ResultsIn contrast to the other machine learning models employed in this study, the XGBoost algorithm exhibited superior predictive performance in identifying mortality risk factors for patients with AL across one, three, and five-year intervals. The analysis identified several common risk factors affecting mortality rates at these intervals, including advanced age, hypoproteinemia, a history of anemia and hypertension, prolonged operative time, increased intraoperative bleeding, low intraoperative percutaneous arterial oxygen saturation (SPO2) levels, T3 and T4 tumors, tumor lymph node invasion, and tumor peripheral nerve invasion (PNI).ConclusionAmong the three machine learning models examined in this study, the XGBoost algorithm exhibited superior predictive capabilities concerning the prognosis of patients with AL following gastrectomy. Additionally, the use of machine learning models offers valuable assistance to clinicians in identifying crucial prognostic factors, thereby enhancing personalized patient monitoring and management.

BackgroundBone health is important for older adults, and vitamin K (VK) is central to regulating bone formation and promoting bone health. However, whether VK can reduce the risk of osteoporosis and bone loss is unclear. This study hypothesized that different levels of VK intake exert varying effects on bone health in people aged over 50 years.MethodsIndividuals aged above 50 years were recruited from the National Health and Nutrition Examination Survey. VK intake, based on 24-h dietary recall, was divided into three groups, namely the high, medium, and low groups, by sex and tertile. Weighted multiple logistic regression was used to investigate the effects of VK intake on the risk of osteoporosis and bone loss at the femoral neck, trochanter, intertrochanter, total femur, lumbar spine, and overall.ResultsThis study included 5,075 individuals. Of them, 1,001 (18%) had osteoporosis (808 women, 83%) and 2,226 (46%) had osteopenia (1,076 women, 54%). Overall, a medium level of VK intake was associated with a reduced risk of bone loss. In women, medium- [odds ratio, OR (95% confidence interval, CI): 0.66(0.47, 0.93)] and high-level [OR (95% CI): 0.71(0.52, 0.98)] VK intake were associated with a decreased risk of osteoporosis. In contrast, only medium-level VK intake was associated with a reduced risk of bone loss [OR (95% CI): 0.58(0.41, 0.81)]. Similar results were obtained for the trochanter, intertrochanter, total femur, and lumbar spine. In men, only medium-level VK intake was associated with a reduced risk of bone loss at the femoral neck [OR (95% CI): 0.66(0.48, 0.90)], whereas high-level VK intake corresponded to a reduced risk of bone loss to the lumbar spine [OR (95% CI): 0.68(0.47, 0.99)]. Nonetheless, VK intake levels did not affect the risk of osteoporosis.ConclusionThis study demonstrates sex- and bone-site-specific variations in the associations between VK intake levels and bone health in individuals aged over 50 years. Further large-scale cohort studies or randomized controlled trials are warranted to explore the effects of different VK intake levels on bone health in people regardless of their sex and bone site.

Bashang suancai is one of the most wellknown traditional fermented vegetables in North China. The study examined the variations in bacterial diversity, physicochemical properties, and volatile flavor compounds (VFCs) of Bashang suancai over a 7-day fermentation period, utilizing Illumina NovaSeq sequencing and headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The leading bacterial phyla were Firmicutes, Proteobacteria, and Cyanobacteria, while the predominant bacterial species included Vibrio, Lactiplantibacillus, Cyanobacteriales, Weissella, and Latilactobacillus. The bacterial community diversity decreased significantly following 7 days of fermentation. The microbial profiles were markedly affected by pH, reducing sugar content (RSC), and salt content (SC). A total of 187 VFCs were identified from the specimens. Following 5 days of fermentation, the taste compounds achieved equilibrium, with isothiocyanates, alcohols, and esters predominating among the volatile molecules. Spearman correlation analysis revealed that a strong link between Latilactobacillus, Levilactobacillus, Lactiplantibacillus, Weissella, and Vibrio with the flavor of pickles. This study established a significant foundation for identifying strains that enhance taste development and improve the nutritional and sensory quality of Bashang suancai.

ObjectiveTo investigate the effect of low-dose rivaroxaban on bleeding events in low-weight patients with nonvalvular atrial fibrillation.MethodsA retrospective study was conducted in patients with nonvalvular atrial fibrillation (weight ≤ 60 kg) who were admitted to the Department of Cardiology of Jiangxi Provincial People's Hospital from June 1, 2022, to December 12, 2022 and received anticoagulant therapy with rivaroxaban. The patients were divided into standard-dose group (15–20 mg) and low-dose group (10–15 mg). The patients were followed up for an average of 15 months by outpatient examination, telephone follow-up, or medical record inquiry of readmission patients. The bleeding events of the two groups were recorded during the follow-up period, and the two groups were balanced by propensity score weighting.ResultsA total of 198 patients with NVAF and body weight ≤60 kg receiving rivaroxaban anticoagulation therapy were enrolled, including 65 patients in the standard-dose group (15–20 mg) and 133 patients in the low-dose group (10–15 mg). In this study, only 24.1% (65/241) of the patients followed the standard dose of rivaroxaban. There was no significant difference in the incidence of bleeding events between the two groups after the balance of baseline characteristics (age) (P > 0.05). This was also consistent in patients weighing less than 50 kg.ConclusionsIn the real world, in lower-weight patients with nonvalvular atrial fibrillation, a reduced dose of rivaroxaban did not reduce the risk of bleeding, and this was consistent in patients weighing less than 50 kg.

BackgroundIntensive care unit (ICU) beds played a crucial role in reducing mortality rates of patients with severe COVID-19. The surge in the number of patients led to a shortage of ICU beds, which may have exacerbated inequity of healthcare utilization. However, most attention has been focused on the horizontal equity in healthcare utilization, where individuals with the same needs receive the same services. Vertical equity, where individuals with higher needs receive more healthcare is often neglected, which might overestimate the equity. This study analyzes the vertical equity of ICU utilization among hospitalized patients with COVID-19.MethodsIn total, 18,547 hospitalized patients with COVID-19 in Maryland in 2020 were enrolled in this cross-sectional study. Logistic regression analysis was conducted to determine the independent factors affecting ICU utilization, and the Shapley value decomposition approach was implemented to assess the contribution of the independent variables to disparities in ICU admission. A concentration curve and concentration index were used to assess the vertical equity in healthcare utilization.ResultsICU utilization by patients with COVID-19 was significantly affected by Charlson Comorbidity Index (CCI), with odds ratios (OR) 1.09 [95% confidence intervals (CI): 1.07–1.10; p

Anthrax is an acute zoonotic infectious disease caused by Bacillus anthracis. It is categorized as a Class B (reported within 24 h of onset, including pulmonary anthrax, which is managed as a Class A infectious disease and reported within 2 h of onset) infectious disease in China. Human anthrax infection primarily occurs through direct or indirect contact with infected animals. This study reports a case of cutaneous anthrax where typical anthrax colonies were observed in conventional microbial cultures, and large Gram-positive rods with squared ends were visible under the microscope. The results from metagenomic next-generation sequencing (mNGS) suggested the presence of Bacillus anthracis. This research explores the value of combining traditional microbiology with mNGS technology for the early diagnosis and therapy of infectious diseases.

To identify rare variants (RVs) of gout, we sequenced the whole genomes of 321 male gout patients and combined these with those of 64 male gout patients and 682 normal controls at Taiwan Biobank. We performed ACAT-O to identify 682 significant RVs (p < 3.8 × 10−8) clustered on chromosomes 1, 7, 10, 16, and 18. To prioritize causal variants effectively, we sifted them by Combined Annotation-Dependent Depletion score >10 or |effect size| ≥ 1.5 for those without CADD scores. In particular, to the best of our knowledge, we identified the rare variants rs559954634, rs186763678, and 13-85340782-G-A for the first time to be associated with gout in Taiwanese males. Importantly, the RV rs559954634 positively affects gout, and its neighboring gene NPHS2 is involved in serum urate and expressed in kidney tissues. The kidneys play a major role in regulating uric acid levels. This suggests that rs559954634 may be involved in gout. Furthermore, rs186763678 is in the intron of NFIA that interacts with SLC2A9, which has the most significant effect on serum urate. Note that gene-gene interaction NFIA-SLC2A9 is significantly associated with serum urate in the Italian MICROS population and a Croatian population. Moreover, 13-85340782-G-A significantly affects gout susceptibility (odds ratio 6.0; P = 0.038). The >1% carrier frequencies of these potentially pathogenic (protective) RVs in cases (controls) suggest the revealed associations may be true; these RVs deserve further studies for the mechanism. Finally, multivariate logistic regression analysis shows that the rare variants rs559954634 and 13-85340782-G-A jointly are significantly associated with gout susceptibility.

ObjectivesSignificant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens.MethodsWe conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis.ResultsNineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39 h−1, 2690 L, and 42.87 L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F.ConclusionOur findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

PurposeTo investigate the predictive value of leukocyte subsets and C-reactive protein (CRP) in coronary artery disease (CAD).MethodsWe conducted a Mendelian randomization analysis (MR) on leukocyte subsets, C-reactive protein (CRP) and CAD, incorporating data from 68,624 patients who underwent coronary angiography from 2010 to 2022. After initial screening, clinical data from 46,664 patients were analyzed. Techniques employed included propensity score matching (PSM), logistic regression, lasso regression, and random forest algorithms (RF). Risk factors were assessed, and the sensitivity and specificity of the models were evaluated using receiver operating characteristic (ROC) curves. Additionally, survival analysis was conducted based on a 36-month follow-up period.ResultsThe inverse variance weight (IVW) analysis showed that basophil count (OR 0.92, 95% CI: 0.84–1.00, P = 0.048), CRP levels (OR 0.87, 95% CI: 0.73–1.00, P = 0.040), and lymphocyte count (OR 1.10, 95% CI: 1.04–1.16, P = 0.001) are significant risk factors for CAD. Using LASSO regression, logistic regression, and RF analysis, both CRP and lymphocyte counts were consistently identified as risk factors for CAD, prior to and following PSM. The ROC curve analysis indicated that the combination of lymphocyte and CRP levels after PSM achieves a higher diagnostic value (0.85). Survival analysis revealed that high lymphocyte counts and low CRP levels are associated with a decreased risk of Major Adverse Cardiovascular Events (MACE) (P

Peritoneal dialysis (PD) is currently one of the effective methods for treating end-stage renal disease (ESRD). However, long-term exposure to high concentration glucose in peritoneal dialysis environment could lead to peritoneal fibrosis (PF), impaired peritoneal filtration function, decreased peritoneal dialysis efficiency, and even withdrawal from peritoneal dialysis in patients. Considerable evidence suggests that peritoneal fibrosis after peritoneal dialysis is related to crucial factors such as mesothelial-to-mesenchymal transition (MMT), inflammatory response, and angiogenesis, etc. In our review, we summarize the pathophysiological mechanisms and further illustrate the future strategies against PF.

ObjectiveTo evaluate the association between musculoskeletal pain and incident sarcopenia and further explore the mediating effect of depressive symptoms among middle-aged and older Chinese adults.MethodsUsing the data from the China Health and Retirement Longitudinal Study 2011 and 2015, we included 12,788 participants in the cross-sectional analysis and 8,322 for the longitudinal analysis. Musculoskeletal pains located in the neck, back, waist, shoulder, arm, wrist, leg, knee, and ankle were self-reported at baseline and follow-up. The diagnosis criteria of sarcopenia was based on the Asian Working Group for Sarcopenia 2019. Multivariable logistic regression models were used to evaluate the association between musculoskeletal pain, and the Karlson–Holm–Breen (KHB) method was used to explore the mediating effect of depressive symptoms.ResultsOver the 4-year follow-up, 445 participants were identified with incident sarcopenia. In the longitudinal analysis, participants with baseline musculoskeletal pain (adjusted odds ratio (OR): 1.37, 95% confidence interval (CI): 1.07–1.76), persistent musculoskeletal pain (OR:1.68, 95%CI: 1.28–2.24), and persistent waist pain (OR:1.46, 95%CI: 1.04–2.03) were significantly associated with increased the risk of incident sarcopenia. Furthermore, depressive symptoms were found to partially mediate the association between musculoskeletal pain and incident sarcopenia.ConclusionPersistent musculoskeletal pain, especially in waist area, was positively associated with a higher risk of sarcopenia among the middle-aged and older Chinese. Depressive symptoms played a partial mediating role in this association.

IntroductionSalicylic acid (SA) is a phenolic compound widely found in plants. It plays a key role in exerting plant disease resistance. Panax vietnamensis Ha & Grushv., a valuable medicinal plant, contains high levels of phenolic compounds, which contribute significantly to the resilience of the plant against stress. However, the precise role of SA in regulating the synthesis of secondary metabolites in P.vietnamensis remains elusive.MethodsTwo-year-old P. vietnamensis seedlings were treated with exogenous SA. We systematically assessed the changes in the physiological parameters of SA-treated P. vietnamensis leaves, employing transcriptome and metabolome analyses to elucidate the underlying mechanisms. ResultsOur results revealed a significant improvement of the plant’s antioxidant capacity at 6 h post-treatment. Furthermore, exogenous SA treatment promoted the biosynthesis of lignin and flavonoids such as rutin, coumarin, and cyanidin. In addition, it increased the levels of endogenous SA and jasmonic acid (JA), promoting the disease resistance of the plants. Thus, SA pretreatment enhanced the defense of P. vietnamensis against pathogens. ConclusionsOur study provided novel insights into the potential molecular mechanisms underlying SA-mediated biosynthesis of secondary metabolites. Furthermore, our results provided a theoretical foundation for optimizing the cultivation practices of P.vietnamensis and the application of SA as a plant immunomodulator.

In recent decades, more and more studies have been conducted on source appointment of heavy metals, since they can accumulate in the food chain and have a negative impact on the ecological environment and human health. However, almost never before had scholars tried to make a comprehensive and methodical review in this field from the scientometric and bibliometric perspective. The purpose of this review is to offer insights into the research topics and trend evaluation in terms of source appointment of heavy metals over time using the visualization and analysis software, CiteSpace. We retrieved a total of 2,533 articles from the Web of Science Core Collection (WoSCC) dated between 1994 and 2022, and analysed the progress, hotspots, and trends in this field by synthesized networks of cooperation analysis, co-citation analysis, keyword co-occurrence and cluster analysis, and keywords burst analysis. The overall development of the topic can be divided into four periods, and the rapid development began from 2010. Environmental Sciences was the leading subject category, and the journal Science of the Total Environment had the highest number of publications (9.51%), which was most cited as well (2,390 times). China published the most articles in this field, in which Chinese Academy of Sciences was the leading institution. Said Muhammad and Xinwei Lu were the top two most productive authors. According to citation frequency, Hakanson L was the movers and shakers. Keyword co-occurrence and cluster analysis results showed that “the health risk assessment,” “lake sediments”, “trace elements,” “positive matrix factorization,” “air pollution,” “road dust,” and “megacity” are likely to be hotspots. The “particulate matter,” “China,” “sediments” and “road dust” demonstrated the research tendencies of this domain by keyword burst analysis.

BackgroundSarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients.MethodsPatients with RA diagnosed between August 2022 and January 2024 were included and randomized into training and validation sets in a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and multifactorial logistic regression analysis were used to screen the risk variables for RA-associated muscle loss and to create an RA sarcopenia risk score. The predictive performance and clinical utility of the risk model were evaluated by plotting the receiver operating characteristic curve and calculating the area under the curve (AUC), along with the calibration curve and clinical decision curve (DCA).ResultsA total of 480 patients with RA were included in the study (90% female, with the largest number in the 45–59 age group, about 50%). In this study, four variables (body mass index, disease duration, hemoglobin, and grip strength) were included to construct a nomogram for predicting RA sarcopenia. The training and validation set AUCs were 0.915 (95% CI: 0.8795–0.9498) and 0.907 (95% CI: 0.8552–0.9597), respectively, proving that the predictive model was well discriminated. The calibration curve showed that the predicted values of the model were basically in line with the actual values, demonstrating good calibration. The DCA indicated that almost the entire range of patients with RA can benefit from this novel prediction model, suggesting good clinical utility.ConclusionThis study developed and validated a nomogram prediction model to predict the risk of sarcopenia in RA patients. The model can assist clinicians in enhancing their ability to screen for RA sarcopenia, assess patient prognosis, make early decisions, and improve the quality of life for RA patients.

IntroductionPanax notoginseng, a medicinal herb in China, is attacked by several pathogens during its cultivation. Dazomet (DZ) is a soil fumigant that is effective in controlling soil-borne pathogens, but its long-term effects on P. notoginseng growth and soil properties are unknown.MethodsWe conducted field experiments over two consecutive years to assess the impact of three concentrations of DZ fumigation (35 kg/666.7 m2, 40 kg/666.7 m2, and 45 kg/666.7 m2) on soil physicochemical properties, microbial diversity, and P. notoginseng growth. Correlation analyses were performed between microbial community changes and soil properties, and functional predictions for soil microorganisms were conducted.ResultsDZ fumigation increased total nitrogen, total phosphorus, total potassium, available phosphorus, available potassium, and ammonia nitrogen levels in the soil. DZ fumigation promoted the nutrient accumulation and improvement of agronomic traits of P. notoginseng, resulted in a 2.83–3.81X yield increase, with the highest total saponin content increasing by 24.06%. And the 40 kg/666.7 m2 treatment had the most favorable impact on P. notoginseng growth and saponin accumulation. After DZ fumigation, there was a decrease in the relative abundance of pathogenic fungi such as Fusarium, Plectosphaerella, and Ilyonectria, while beneficial bacteria such as Ramlibacter, Burkholderia, and Rhodanobacteria increased. The effects of fumigation on soil microorganisms and soil physicochemical properties persisted for 18 months post-fumigation. DZ fumigation enhanced the relative abundance of bacteria involved in the biosynthesis of secondary metabolites and arbuscular mycorrhizal fungi, reduced the relative abundance of plant–animal pathogenic fungi, reduced the occurrence of soil-borne diseases.ConclusionIn conclusion, DZ fumigation enhanced soil physicochemical properties, increased the proportion of beneficial bacteria in the soil, and rebalanced soil microorganism populations, consequently improving the growth environment of P. notoginseng and enhancing its growth, yield, and quality. This study offers a theoretical foundation for DZ fumigation as a potential solution to the continuous cropping issue in perennial medicinal plants such as P. notoginseng.

Freshwater pollution is a global challenge that citizens recognise as unacceptable, despite professional efforts to monitor, manage, and regulate it. Water quality is difficult to observe at high spatial and temporal resolutions; it is costly and typically requires trained specialists in the field and in laboratories. However, the rise in citizen science monitoring has generated opportunities to overcome many barriers and fill data gaps. Citizens want access to actionable water quality information that can provide early warnings and drive change. Our bibliographic analysis emphasises that citizen science is rarely paired with the use of continuous sensors, and many monitoring schemes involving the public are unable to offer the detail required. This study has explored the practicalities and competencies associated with community-led (near) continuous water quality monitoring (CWQM), and has generated an extensive checklist containing technical, social, economic, and wider responsibilities that stakeholders should consider. The “UpStream” project has provided a testbed for this exploratory work and the development and deployment of the “WaterBox” CWQM device. Case studies from the UK and Taiwan, where community-led CWQM programmes have been piloted, have provided novel methodological insights. Lessons learnt have enabled researchers to determine whether, and to what extent, community-led CWQM is achievable in practice. Results confirm that 75% of the practicalities observed fall under the “technical” category, despite offering a social and inclusive methodology. Through observational work, it was found that only 34% of the 104 practicalities were led by community groups and community champions. Communities require significant support owing to the sheer number of technical barriers, although some of this could be provided by skilled community champions. These findings have surfaced despite the WaterBox equipment being open, accessible, cost-effective, and adaptable. Unless support is in place and/or technology significantly evolves to reduce the number of challenges, it is unlikely that communities will lead and take full ownership of CWQM programmes. Despite this, the generation of site-specific CWQM data are welcomed by citizens, who can co-design schemes, interpret trends and offer valuable local information that trained scientists cannot achieve alone. These transferable findings are relevant to monitoring initiatives across the environmental sector.

Fine-grained classification of tree species by using high-spectral image data has garnered considerable attention from scholars. In this study, through field measurements from Maguan County, Wenshan Prefecture, Yunnan Province, China, high-spectral image data from the Chinese Resource-1 02D satellite were used as the data source. Various analyses were conducted on the original image’s spectral curve, the spectral curve after envelope removal, the spectral curve after first-order differential transformation, and the spectral curve after second-order differential transformation. A spectral angle mapping classification method was employed to classify and identify four dominant tree species in Maguan County, and the accuracy of the classification results was validated using a confusion matrix. Results indicate that the highest accuracy in tree species classification was achieved when first-order differential transformation and envelope removal were used for the spectral curve; the overall accuracy exceeded 95%, and the kappa value was approximately 0.95. The classification results for the spectral curve after second-order differential transformation were the lowest, with an overall accuracy of 81.69% and a kappa value of 0.76. This research demonstrates that applying first-order differential transformation or envelope removal in combination with spectral angle mapping classification considerably reduces data processing time and improves tree species classification accuracy.

IntroductionThis paper was to assess the diagnostic performance and clinical value of three-dimensional ultrasonography (3DUS), three-dimensional ultrasonography power Doppler (3DPD), and 3DUS combined with 3DPD in ovarian cancer (OC).MethodsThe study was registered with PROSPERO (CRD 42023405765). PubMed and Web of Science were searched from inception to 25 January 2022, and reference lists of potentially eligible studies were also manually searched. Patient and study characteristics were extracted by two independent reviewers. Any discrepancies were addressed through discussion. The sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR, respectively), and the area under the receiver operating characteristic curve (AUC) were pooled separately.ResultsWe retrieved 2,566 studies, of which 18 were finally enrolled, with 2,548 cases. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DUS were 0.89 (95% CI: 0.85–0.93), 0.93 (95% CI: 0.88–0.96), 13.1 (95% CI: 7.3–23.4), 0.11 (95% CI: 0.08–0.16), and 0.90 (95% CI: 0.87–0.93), respectively. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DPD were 0.90 (95% CI: 0.80–0.95), 0.85 (95% CI: 0.71–0.92), 5.8 (95% CI: 3.0–11.2), 0.12 (95% CI: 0.06–0.24), and 0.94 (95% CI: 0.91–0.96), respectively. The pooled sensitivity, specificity, PLR, NLR, and AUC for 3DUS combined with 3DPD were 0.99 (95% CI: 0.73–1.00), 0.95 (95% CI: 0.85–0.99), 21.9 (95% CI: 6.1–78.9), 0.01 (95% CI: 0.00–0.37), and 0.99 (95% CI: 0.98–1.00), respectively.Conclusions3DUS, 3DPD, and 3DUS combined with 3DPD are promising diagnostic tools for OC, alongside elevated sensitivity and specificity. However, the combination of 3DUS and 3DPD techniques has higher diagnostic efficiency.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42023405765.

IntroductionA variety of studies have shown a link between the gut microbiota and autoimmune diseases, but the causal relationship with Henoch-Schönlein purpura (HSP) and immune thrombocytopenic purpura (ITP) is unknown.MethodsThis study investigated the bidirectional causality between gut microbiota and HSP and ITP using Mendelian randomization (MR). Large-scale genetic data of gut microbiota at phylum to species level from the MiBioGen consortium and the Dutch Microbiome Project were utilized. Genome-wide association studies (GWAS) summary statistics for HSP and ITP came from FinnGen R10. Various MR methods were applied to infer causal relationships, including inverse variance weighted (IVW), maximum likelihood (ML), cML-MA, MR-Egger, weighted median, weighted model, and MR-PRESSO. Multiple sensitivity analyses and Bonferroni correction were conducted to enhance robustness and reliability.ResultsBased on the IVW estimates, 23 bacterial taxa were identified to have suggestive associations with HSP and ITP. Remarkably, after Bonferroni correction, family Alcaligenaceae (OR = 2.86, 95% CI = 1.52–5.37; IVW, p = 1.10 × 10−3, ML, p = 1.40 × 10−3) was significantly associated with ITP as a risk factor, while family Bacteroidales S24 7group (OR = 0.46, 95% CI = 0.29–0.74; IVW, p = 1.40 × 10−3) was significantly associated with ITP as a protective factor. No significant associations between HSP and ITP and gut microbiota were found in reverse analyses.ConclusionOur study provides evidence of causal effects of gut microbiota on HSP and ITP, highlighting the importance of further research to clarify the underlying mechanisms and develop targeted therapeutic interventions for these autoimmune diseases.

BackgroundOur study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21–1 (CYFRA21–1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).MethodsA total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram’s net benefits at various threshold probabilities.ResultsSix variables, including CYFRA21–1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer–Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21–1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19–9 (Log CA19–9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21–1 was greater than that of the other variables used as diagnostic biomarkers.ConclusionsThis study developed and validated a nomogram including CYFRA21–1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.

IntroductionPanax ginseng C. A. Mey. (Araliaceae; Ginseng Radix et Rhizoma), a traditional plant commonly utilized in Eastern Asia, has demonstrated efficacy in treating neuro-damaging diseases and diabetes mellitus. However, its precise roles and mechanism in alleviating type 2 diabetes mellitus (T2DM) need further study. The objective of this study is to explore the pharmacological effects of ginseng extract and elucidate its potential mechanisms in protecting islets and promoting β-cell regeneration.MethodsThe T2DM mouse model was induced through streptozotocin combined with a high-fat diet. Two batches of mice were sacrificed on the 7th and 28th days following ginseng extract administration. Body weight, fasting blood glucose levels, and glucose tolerance were detected. Morphological changes in the pancreatic islets were examined via H & E staining. Levels of serum insulin, glucagon, GLP-1, and inflammatory factors were measured using ELISA. The ability of ginseng extract to promote pancreatic islet β-cell regeneration was evaluated through insulin & PCNA double immunofluorescence staining. Furthermore, the mechanism behind β-cells regeneration was explored through insulin & glucagon double immunofluorescence staining, accompanied by immunohistochemical staining and western blot analyses.Results and DiscussionThe present research revealed that ginseng extract alleviates symptoms of T2DM in mice, including decreased blood glucose levels and improved glucose tolerance. Serum levels of insulin, GLP-1, and IL-10 increased following the administration of ginseng extract, while levels of glucagon, TNF-α, and IL-1β decreased. Ginseng extract preserved normal islet morphology, increased nascent β-cell population, and inhibited inflammatory infiltration within the islets, moreover, it decreased α-cell proportion while increasing β-cell proportion. Mechanistically, ginseng extract might inhibit ARX and MAFB expressions, increase MAFA level to aid in α-cell to β-cell transformation, and activate AKT-FOXM1/cyclin D2 to enhance β-cell proliferation. Our study suggests that ginseng extract may be a promising therapy in treating T2DM, especially in those with islet injury.

Long non-coding RNAs (lncRNAs) are a sort of transcripts that are more than 200 nucleotides in length. In recent years, many studies have revealed the modulatory role of lncRNAs in cancer. Typically, lncRNAs are linked to a variety of essential events, such as apoptosis, cellular proliferation, and the invasion of malignant cells. Simultaneously, autophagy, an essential intracellular degradation mechanism in eukaryotic cells, is activated to respond to multiple stressful circumstances, for example, nutrient scarcity, accumulation of abnormal proteins, and organelle damage. Autophagy plays both suppressive and promoting roles in cancer. Increasingly, studies have unveiled how dysregulated lncRNAs expression can disrupt autophagic balance, thereby contributing to cancer progression. Consequently, exploring the interplay between lncRNAs and autophagy holds promising implications for clinical research. In this manuscript, we methodically compiled the advances in the molecular mechanisms of lncRNAs and autophagy and briefly summarized the implications of the lncRNA-mediated autophagy axis.

BackgroundSmoking is a risk factor for a wide range of diseases. Previous research has confirmed over 30 Smoking-Associated Diseases in diverse systems. There is limited research exploring the correlation among multiple diseases, with an absence of comprehensive investigations. Few studies concentrate on diseases exhibiting a negative correlation with smoking, wherein smokers demonstrate a lower prevalence.ObjectiveThis study aimed to detect the correlation between smoking and other diseases using data from National Health and Nutrition Examination Surveys (NHANES) and construct a Smoking-Diseases Correlation Database (SDCD). The second aim is to obtain an extensive screening test for diseases that may be linked to smoking.Methods39,126 subjects’ data from the NHANES 2013–2018 dataset were extracted. The baseline information, difference in blood routine and blood chemistry indicators between smokers and non-smokers, and diseases’ correlation with smoking in four different models were analyzed by R. The data and statistics were aggregated into an online SDCD.ResultsOur study reported 46 Smoking-Associated Diseases (SAD), including 29 Smoking Positively Associated Diseases (SPAD) and 17 Smoking Negatively Associated Diseases (SNAD). The SDCD of 422 diseases was constructed and can be accessed at https://chatgptmodel.shinyapps.io/sdcd/.ConclusionOur findings revealed 46 SADs including 29 SPADs and 17 SNADs. We aggregated the statistics and developed online SDCD, advancing our understanding of the correlation between smoking and diseases.

ObjectiveThe purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsThis study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.ResultsA total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.ConclusionIn summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.

Alzheimer’s disease psychosis (ADP) produces a significant burden for patients and their care partners, but at present there are no approved treatments for ADP. The lack of approved treatments may be due to the challenges of conducting clinical trials for this disease. This perspective article discusses distinct challenges and proposed solutions of conducting ADP trials involving seven key areas: (1) methods to reduce the variable and sometimes high rates of placebo response that occur for treatments of neuropsychiatric symptoms; (2) the use of combined or updated criteria that provide a precise, consensus definition of ADP; (3) the use of eligibility criteria to help recruit individuals representative of the larger ADP population and overcome the difficulty of recruiting patients with moderate-to-severe ADP; (4) consideration of multiple perspectives and implementation of technology to reduce the variability in the administration and scoring of neuropsychiatric symptom assessments; (5) the use of clinically appropriate, a priori–defined severity thresholds and responder cutoffs; (6) the use of statistical approaches that address absolute effect sizes and a three-tier approach to address the fluctuation of neuropsychiatric symptoms; and (7) the implementation of feasible diagnostic and target-engagement biomarkers as they become available. The goal of these proposed solutions is to improve the evaluation of potential ADP therapies, within the context of randomized, placebo-controlled trials with clinically meaningful endpoints and sustained treatment responses.

IntroductionIschemic stroke (IS) is a cerebrovascular disease that can be disabling and fatal, and there are limitations in the clinical treatment and prognosis of IS. It has been reported that changes in the expression profile of circRNAs have been found during injury in ischemic stroke, and circRNAs play an important role in the IS cascade response. However, the specific mechanisms involved in the pathogenesis of IS are not yet fully understood, and thus in-depth studies are needed.MethodsIn this study, one circRNA dataset (GSE161913), one miRNA dataset (GSE60319) and one mRNA dataset (GSE180470) were retrieved from the Gene Expression Omnibus (GEO) database and included, and the datasets were differentially expressed analyzed by GEO2R and easyGEO to get the DEcircRNA, DEmiRNA and DEmRNA, and DEmRNA was enriched using ImageGP, binding sites were predicted in the ENCORI database, respectively, and the competitive endogenous RNA (ceRNA) regulatory network was visualized by the cytoscape software, and then selected by MCC scoring in the cytoHubba plugin Hub genes. In addition, this study conducted a case–control study in which blood samples were collected from stroke patients and healthy medical examiners to validate the core network of ceRNAs constructed by biosignature analysis by real-time fluorescence quantitative qRT-PCR experiments.ResultsA total of 233 DEcircRNAs, 132 DEmiRNAs and 72 DEmRNAs were screened by bioinformatics analysis. circRNA-mediated ceRNA regulatory network was constructed, including 148 circRNAs, 43 miRNAs and 44 mRNAs. Finally, CLEC16A|miR-654-5p|RARA competitive endogenous regulatory axis was selected for validation by qRT-PCR, and the validation results were consistent with the bioinformatics analysis.DiscussionIn conclusion, the present study establishes a new axis of regulation associated with IS, providing new insights into the pathogenesis of IS.

BackgroundMalignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature.Case summaryA 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative. Pelvic color Doppler ultrasound exhibited incomplete mediastinal uterus and heterogeneous echo from the cervical canal to the posterior wall of the cervix. Pelvic contrast-enhanced CT showed left cervical mass, left retroperitoneal mass, absence of the left kidney, and mediastinal uterus. An increase in human epididymal protein 4 (HE4) (133.6 pmol/L) was detected, while other tumor markers were at normal levels. Based on these examination results, a diagnosis of “cervical fibroids, left retroperitoneal mass, incomplete mediastinal uterus, left kidney deficiency”[SIC] was conducted, and expanded hysterectomy, right adnexectomy, and left retroperitoneal mass resection were performed. Through intraoperative rapid pathological diagnosis, postoperative pathological diagnosis combined with the re-evaluation of laboratory, and imaging and intraoperative examination results, the patient was diagnosed with ureteric bud intestinal-type adenocarcinoma involving the cervix. The patient has been tracked and followed up for approximately 11 months. She underwent six courses of chemotherapy. At present, the medication has been discontinued for 4 months, and there is no recurrence, metastasis, or deterioration of the tumor.ConclusionFor large masses of the cervix, it is feasible for the operation to be performed, improving the prognosis. There were a few limitations. A preoperative aspiration biopsy of masses was not performed to differentiate benign from malignant. Preoperative urography was not performed to clarify the function of the malformed urinary system structure. Partial cystectomy should be performed simultaneously with the resection of the ureteric bud for intestinal-type adenocarcinoma. In this case, a partial cystectomy was not performed, which can only be compensated with postoperative chemotherapy. Moreover, this patient did not undergo genetic screening, and it is currently unclear whether there are any genetic mutations associated with ureteric bud intestinal adenocarcinoma.

The complexity of crude oil composition, combined with the fluctuating oxygen level in contaminated environments, poses challenges for the bioremediation of oil pollutants, because of compound-specific microbial degradation of petroleum hydrocarbons under certain conditions. As a result, facultative bacteria capable of breaking down petroleum hydrocarbons under both aerobic and anaerobic conditions are presumably effective, however, this hypothesis has not been directly tested. In the current investigation, Shewanella putrefaciens CN32, a facultative anaerobic bacterium, was used to degrade petroleum hydrocarbons aerobically (using O2 as an electron acceptor) and anaerobically (using Fe(III) as an electron acceptor). Under aerobic conditions, CN32 degraded more saturates (65.65 ± 0.01%) than aromatics (43.86 ± 0.03%), with the following order of degradation: dibenzofurans > n-alkanes > biphenyls > fluorenes > naphthalenes > alkylcyclohexanes > dibenzothiophenes > phenanthrenes. In contrast, under anaerobic conditions, CN32 exhibited a higher degradation of aromatics (53.94 ± 0.02%) than saturates (23.36 ± 0.01%), with the following order of degradation: dibenzofurans > fluorenes > biphenyls > naphthalenes > dibenzothiophenes > phenanthrenes > n-alkanes > alkylcyclohexanes. The upregulation of 4-hydroxy-3-polyprenylbenzoate decarboxylase (ubiD), which plays a crucial role in breaking down resistant aromatic compounds, was correlated with the anaerobic degradation of aromatics. At the molecular level, CN32 exhibited a higher efficiency in degrading n-alkanes with low and high carbon numbers relative to those with medium carbon chain lengths. In addition, the degradation of polycyclic aromatic hydrocarbons (PAHs) under both aerobic and anaerobic conditions became increasingly difficult with increased numbers of benzene rings and methyl groups. This study offers a potential solution for the development of targeted remediation of pollutants under oscillating redox conditions.

IntroductionMacrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages.MethodsHE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment.ResultsIn this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What’s more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth.DiscussioniBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

IntroductionInterleukin-2 (IL-2) is one of the first cytokines to be discovered as an immune agonist for cancer immunotherapy. Biased IL-2 variants had been discovered to eliminate Treg activation or enhance the tumor specific T cell cytotoxicity. However, all the biased IL-2 variants pose the risk to overstimulate immune response at a low-dose range. Here, we introduce a novel dual-MOA bispecific PD-1-IL-2v molecule with great anti-tumor efficacy in a high dosed manner.MethodsThe novel IL-2 variant was designed by structural truncation and shuffling. The single armed bispecific PD-1-IL-2v molecule and IL-2v were studied by immune cell activations in vitro and in vivo and anti-tumor efficacy in mouse model.Results and discussionThe IL-2 variant in this bispecific antibody only binds to IL-2Rβγ complex in a fast-on/off manner without α, β or γ single receptor binding. This IL-2v mildly activates T and NK cells without over stimulation, meanwhile it diminishes Treg activation compared to the wild type IL-2. This unique bispecific molecule with “βγ-only” IL-2v can not only “in-cis” stimulate and expand CD8 T and NK cells moderately without Treg activation, but also block the PD-1/L1 interaction at a similar dose range with monoclonal antibody.

IntroductionDifenoconazole (DIFE) is a common pesticide used in citrus cultivation; excessive intake can cause neurological damage to the organism, and the existing colloidal gold immunochromatographic test strips cannot meet the requirements for the detection of citrus samples.MethodsDifenoconazole test strip was prepared based on the colloidal gold immunochromatographic technique (GICT), and its application in citrus samples was investigated; with colloidal gold (CG) as the probe, the optimization of GICT parameters, and the determination of reaction method, the immunochromatographic test strips for the detection of DIFE in citrus was developed, and the limit of detection (LOD), specificity, accuracy, and stability of the test strips were verified.ResultsThe results showed that the visual detection limit of the prepared colloidal gold immunochromatographic test strips was 0.2 mg/kg and the quantitative range was 0.06–0.6 mg/kg, and the test strips could specifically identify DIFE and have no cross-reaction with other common triazole pesticides. The detection method established in this study was verified by the GC–MS method, and the detection results achieved good consistency (R2 > 0.98).ConclusionThe test strips developed in this study have good performance and can be used for highly sensitive detection of citrus samples.

Guiding rural residents to implement interpersonal waste separation in their daily lives consciously is crucial for controlling solid waste pollution in developing countries. This paper utilizes survey data from Jiangxi Province which is one of the national pilot zones for ecological conservation in China to analyze the impact of the social capital that includes social networks, social trust, and social norms on the rural residents’ conscious interpersonal waste separation behavior. The empirical results indicate that social capital has a positive effect on the rural residents’ conscious interpersonal waste separation behavior, wherein the effects of social networks and social trust are significant. Among the three dimensions of social capital, social networks and social norms are substitutable, while social trust and social norms have a complementary effect on each other. Moreover, the ecological cognition and subjective norm play a significant mediating role in the relationship between social network, social trust, and social norms and the rural residents’ conscious interpersonal waste separation behavior, while the government policies plays a significant moderating effect.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, representing a major cause of liver disease worldwide. This condition spans a spectrum of histopathologic stages, beginning with simple fatty liver (MAFL), characterized by over 5% fat accumulation, and advancing to metabolic (dysfunction)-associated steatohepatitis, potentially leading to hepatocellular carcinoma. Despite extensive research, there remains a substantial gap in effective therapeutic interventions. This condition’s progression is closely tied to micronutrient levels, crucial for biological functions like antioxidant activities and immune efficiency. The levels of these micronutrients exhibit considerable variability among individuals with MAFLD. Moreover, the extent of deficiency in these nutrients can vary significantly throughout the different stages of MAFLD, with disease progression potentially exacerbating these deficiencies. This review focuses on the role of micronutrients, particularly vitamins A, D, E, and minerals like iron, copper, selenium, and zinc, in MAFLD’s pathophysiology. It highlights how alterations in the homeostasis of these micronutrients are intricately linked to the pathophysiological processes of MAFLD. Concurrently, this review endeavors to harness the existing evidence to propose novel therapeutic strategies targeting these vitamins and minerals in MAFLD management and offers new insights into disease mechanisms and treatment opportunities in MAFLD.

BackgroundPrevious research has yielded conflicting results on the link between epilepsy risk and lipid-lowering medications. The aim of this study is to determine whether the risk of epilepsy outcomes is causally related to lipid-lowering medications predicted by genetics.MethodsWe used genetic instruments as proxies to the exposure of lipid-lowering drugs, employing variants within or near genes targeted by these drugs and associated with low-density lipoprotein cholesterol (LDL cholesterol) from a genome-wide association study. These variants served as controlling factors. Through drug target Mendelian randomization, we systematically assessed the impact of lipid-lowering medications, including HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and Niemann-Pick C1-like 1 (NPC1L1) inhibitors, on epilepsy.ResultsThe analysis demonstrated that a higher expression of HMGCR was associated with an elevated risk of various types of epilepsy, including all types (OR = 1.17, 95% CI:1.03 to 1.32, p = 0.01), focal epilepsy (OR = 1.24, 95% CI:1.08 to 1.43, p = 0.003), and focal epilepsy documented with lesions other than hippocampal sclerosis (OR = 1.05, 95% CI: 1.01 to 1.10, p = 0.02). The risk of juvenile absence epilepsy (JAE) was also associated with higher expression of PCSK9 (OR = 1.06, 95% CI: 1.02 to 1.09, p = 0.002). For other relationships, there was no reliable supporting data available.ConclusionThe drug target MR investigation suggests a possible link between reduced epilepsy vulnerability and HMGCR and PCSK9 inhibition.

ObjectiveThis sought to explore the association between soybean product consumption and executive function (EF) in Chinese Tibetan adolescents in high-altitude areas.MethodsA total of 1,184 Tibetan children and adolescents were tested on demographic variables, soybean product consumption, and executive function in Lhasa and Nagchu regions of Tibet, China, using stratified whole population sampling. One-way ANOVA, linear regression analysis, and logistic regression analysis were used to analyze the associations existing between soybean product consumption and executive function.ResultsThe proportions of Hardly ever, Occasionally, and Often in Soy Consumption among Tibetan children and adolescents in high altitude areas of Tibet, China were 21.7, 50.3, and 28.0%, respectively. The difference in 2 back reaction time among Tibetan children and adolescents with different soybean product consumption was statistically significant (F = 6.374, p = 0.002). The difference in conversion function reaction time was also statistically significant (F = 8.129, p

BackgroundGlioma pathogenesis related-2 (GLIPR2), an emerging Golgi membrane protein implicated in autophagy, has received limited attention in current scholarly discourse.MethodsLeveraging extensive datasets, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we conducted a comprehensive investigation into GLIPR2 expression across diverse human malignancies. Utilizing UALCAN, OncoDB, MEXPRESS and cBioPortal databases, we scrutinized GLIPR2 mutation patterns and methylation landscapes. The integration of bulk and single-cell RNA sequencing facilitated elucidation of relationships among cellular heterogeneity, immune infiltration, and GLIPR2 levels in pan-cancer. Employing ROC and KM analyses, we unveiled the diagnostic and prognostic potential of GLIPR2 across diverse cancers. Immunohistochemistry provided insights into GLIPR2 expression patterns in a multicenter cohort spanning various cancer types. In vitro functional experiments, including transwell assays, wound healing analyses, and drug sensitivity testing, were employed to delineate the tumor suppressive role of GLIPR2.ResultsGLIPR2 expression was significantly reduced in neoplastic tissues compared to its prevalence in healthy tissues. Copy number variations (CNV) and alterations in methylation patterns exhibited discernible correlations with GLIPR2 expression within tumor tissues. Moreover, GLIPR2 demonstrated diagnostic and prognostic implications, showing pronounced associations with the expression profiles of numerous immune checkpoint genes and the relative abundance of immune cells in the neoplastic microenvironment. This multifaceted influence was evident across various cancer types, with lung adenocarcinoma (LUAD) being particularly prominent. Notably, patients with LUAD exhibited a significant decrease in GLIPR2 expression within practical clinical settings. Elevated GLIPR2 expression correlated with improved prognostic outcomes specifically in LUAD. Following radiotherapy, LUAD cases displayed an increased presence of GLIPR2+ infiltrating cellular constituents, indicating a notable correlation with heightened sensitivity to radiation-induced therapeutic modalities. A battery of experiments validated the functional role of GLIPR2 in suppressing the malignant phenotype and enhancing treatment sensitivity.ConclusionIn pan-cancer, particularly in LUAD, GLIPR2 emerges as a promising novel biomarker and tumor suppressor. Its involvement in immune cell infiltration suggests potential as an immunotherapeutic target.

Silicon (Si) and boron (B) are a class of elements called metalloids, which have properties like metals and non-metals. Si is classified as a quasi-essential element, while B is a micronutrient element for plants. Nowadays, numerous discoveries have shown the analogy of silicon and boron in plant nutrition. In this minireview, the molecular mechanisms for the transport of these two metalloids are compared. We also discussed the chemical forms of Si and B and their functional similarity in response to environmental stresses in plants. In conclusion, it can be proposed that cell wall-bound silicon rather than silica might partially replace boron for plant growth, development, and stress responses, and the underlying mechanism is the Si contribution to B in its structural function.

Disturbances in immunoregulation may lead to both cancer and autoimmune diseases. Many therapeutic drugs for autoimmune diseases also display anti-tumor efficacy. The Janus kinase/signal transducer and activator of transcription signaling pathways are involved in the secretion of more than 50 distinct cytokines, which have critical roles in inducing autoimmune diseases and tumorigenesis. Thus, Janus kinases have become classical immunotherapeutic targets for immune disease. More than 70 Janus kinase inhibitors have been approved as immunomodulatory drugs for clinical use, of which 12 are used in the treatment of autoimmune diseases. This systematic review aims to elucidate the anti-tumor role of clinically approved Janus kinase inhibitors that were primarily designed for the treatment of autoimmune diseases and their potential for clinical translation as cancer treatments.

Objectives: This study aims to identify the key senescence genes and potential regulatory mechanisms that contribute to the etiology of intervertebral disc degeneration (IDD).Method: We analyzed GSE34095 and GSE70362 datasets, identifying key senescence-related differentially expressed genes (DEGs) in IDD using lasso regression. Risk scores classified patients into high- and low-risk groups. We compared pathways, functions, and immune infiltration between these groups. Diagnostic ability was assessed using ROC curves and a nomogram predicted IDD incidence. In single-cell dataset GSE165722, we evaluated expression of key senescence-related DEGs.Results: We identified 12 key senescence-related DEGs distinguishing high- and low-risk IDD patients. Enrichment analysis revealed cellular stress response, apoptotic signaling pathway, and protein kinase activation differences. Immune cell analysis showed elevated eosinophils in low-risk group and increased effector memory CD8 T, central memory CD4 T, myeloid-derived suppressor, natural killer, monocyte, Type 1 T helper, plasmacytoid dendritic, and natural killer T cells in high-risk group. A nomogram using AUC >0.75 genes (CXCL8, MAP4K4, MINK1, and TNIK) predicted IDD incidence with good diagnostic power. High senescence scores were observed in neutrophils.Conclusion: Our diagnostic model, based on key senescence-related DEGs and immune cell infiltration, offers new insights into IDD pathogenesis and immunotherapy strategies.

Japanese encephalitis (JE) is a naturally occurring localized disease caused by the Japanese encephalitis virus, which is spread by the Culex tritaeniorhynchus. China has a high rate of JE. Shanxi, located in North China, has a high prevalence of adult JE. Adult JE has more severe complications, mortality, and a higher disease burden, making it a public health issue. This retrospective study examined the dynamic epidemic changes, high-risk areas of JE, and clinical characteristics and prognostic factors of adult JE in Shanxi Province. The findings revealed that July to September was the primary epidemic season of JE and that JE cases were mainly in individuals over the age of 40. The incidence of JE from 2005 to 2022 demonstrated a positive spatial correlation with significant clustering characteristics, with high-incidence clusters in the south and southeast. Multivariate logistic regression analysis revealed that higher cerebrospinal fluid pressure, higher white blood cell counts, higher neutrophil percentage, deep coma, and lower albumin were independent factors for poor prognosis of adult JE. The developed risk prediction model holds great promise in early prognosis assessment of patients, providing a basis for clinical decision-making and early clinical intervention.

IntroductionInsomnia is the most common form of sleep deprivation (SD) observed in clinics. Although there are differences between insomnia and SD, they have similar symptoms and the same animal model. Currently, there is a lack of microarray data on insomnia. Therefore, for now, we are going to apply the SD data to insomnia. Although many studies have explained the possible mechanisms associated with insomnia, no previous studies have considered the key genes associated with insomnia or the relationship between insomnia and immune cells. In this study, we analyzed the relationship between key genes and immune cells by identifying biomarkers for the diagnosis of insomnia. Next, we verified the efficacy of these biomarkers experimentally.MethodsFirst, we downloaded four microarrays (GSE11755, GSE12624, GSE28750, and GSE48080) from the Gene Expression Omnibus (GEO) database, which included data from 239 normal human blood samples and 365 blood specimens from patients with SD. Then, we analyzed two groups of differentially expressed genes (DEGs) and used Support Vector Machine Recursive Feature Elimination (SVM-RFE) analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model to investigate these key genes. Next, we used CIBERSORT to investigate the composition of 22 immune cell components of key genes in SD patients. Finally, the expression levels of key biomarkers in sleep-deprived patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsA total of 50 DEGs were identified: six genes were significantly upregulated, and 44 genes were significantly downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that Salmonella infection, NOD-like receptor (NLR) signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and Th17 cell differentiation were significant. Based on machine learning, we identified C2CD2L, SPINT2, APOL3, PKNOX1, and A2M as key genes for SD; these were confirmed by receiver operating characteristic (ROC) analysis. Immune cell infiltration analysis showed that C2CD2L, SPINT2, APOL3, PKNOX1, and A2M were related in different degrees to regulatory T cells (Tregs), follicular T helper cells, CD8 cells, and other immune cells. The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not.DiscussionIn summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.

Glycolysis is the preferred energy metabolism pathway in cancer cells even when the oxygen content is sufficient. Through glycolysis, cancer cells convert glucose into pyruvic acid and then lactate to rapidly produce energy and promote cancer progression. Changes in glycolysis activity play a crucial role in the biosynthesis and energy requirements of cancer cells needed to maintain growth and metastasis. This review focuses on ovarian cancer and the significance of key rate-limiting enzymes (hexokinase, phosphofructokinase, and pyruvate kinase, related signaling pathways (PI3K-AKT, Wnt, MAPK, AMPK), transcription regulators (HIF-1a), and non-coding RNA in the glycolytic pathway. Understanding the relationship between glycolysis and these different mechanisms may provide new opportunities for the future treatment of ovarian cancer.

IntroductionThe experience and perception of stigma is a common problem among primary caregivers of children with autism spectrum disorder (ASD), and has a profound adverse impact on primary caregivers and children with ASD; however, few studies have explored courtesy stigma among primary caregivers of children with ASD in the Chinese context. The aim of this study was to explore the status of courtesy stigma among primary caregivers of children with ASD in Lianyungang, Jiangsu Province, Eastern China, and to conduct in-depth analysis of its predictors from multiple perspectives.MethodsAn institution-based multi-center cross-sectional survey was conducted in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China, from October 2022 to February 2023. A structured questionnaire to assess child-related factors, primary caregiver-related factors, courtesy stigma, general self-efficacy, and social support, was used to collect data. Predictors of courtesy stigma among primary caregivers of children with ASD were identified by linear regression.ResultsA total of 428 primary caregivers of children with ASD were recruited. The mean ± standard deviation (SD) score for courtesy stigma was 7.49 ± 4.13. Multiple linear regression analysis revealed that primary caregivers of children with ASD who were not too satisfied with their current marital status (β = 1.21, 95% CI: 0.34–2.08, p

BackgroundGlaucoma is one of the main causes of irreversible visual field loss and blindness worldwide. Vision loss in this multifactorial neurodegenerative disease results from progressive degeneration of retinal ganglion cells (RGCs) and their axons. Identifying molecular markers that can be measured objectively and quantitatively may provide essential insights into glaucoma diagnosis and enhance pathophysiology understanding.MethodsThe chronic, progressive DBA/2J glaucomatous mouse model of glaucoma and C57BL6/J optic nerve crush (ONC) mouse model were used in this study. Changes in PVALB expression with RGC and optic nerve degeneration were assessed via gene expression microarray analysis, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry.ResultsMicroarray analysis of the retinal gene expression in the DBA/2J mice at different ages showed that the expression of PVALB was downregulated as the mice aged and developed glaucoma with retinal ganglion cell loss. Analysis of qRT-PCR results demonstrated PVALB at the mRNA level was reduced in the retinas and optic nerves of old DBA/2J mice and in those after ONC compared to baseline young DBA2/J mice. PVALB protein expression measured by Western blot was also significantly reduced signal in the retinas and optic nerves of old DBA/2J mice and those eyes with crushed nerves. Immunohistochemical staining results demonstrated that there were fewer PVALB-positive cells in the ganglion cell layer (GCL) of the retina and staining pattern changed in the optic nerve from old DBA/2J mice as well as in mice eyes following ONC.ConclusionPVALB is abundantly expressed both by RGCs’ soma in the retinas and RGCs’ axons in the optic nerves of C57BL/6J. Furthermore, the expression level of PVALB decreases with RGC degeneration in the glaucomatous DBA/2J mice and after ONC injury of C57BL6/6J, indicating that PVALB is a reliable RGC molecular marker that can be used to study retinal and optic nerve degeneration.

BackgroundSelective lateral lymph node (LLN) dissection with total mesorectal excision after neoadjuvant chemoradiotherapy (nCRT) is pointed out to reduce lateral compartment recurrence and to improve survival in patients with rectal cancer with LLN metastases. This study aimed to explore the safety, surgical indications, and survival outcomes of LLN dissection after nCRT.MethodsThis multicenter retrospective study included patients with rectal cancer with clinical evidence of LLN metastases (n = 466) treated across three hospitals in China. Patients who underwent total mesorectal excision and LLN dissection were grouped into nCRT (n = 155) and non-nCRT (n = 291), respectively. Propensity score matching was used to minimize selection bias.ResultsAfter matching, nCRT did not significantly increase the surgery duration, intraoperative blood loss or postoperative complications (P > 0.05). In a multivariate logistic regression analysis, poor/mucinous/signet adenocarcinoma (P = 0.042) and post-nCRT LLN short diameter ≥7 mm (P < 0.001) were independent risk factors for pathological LLN metastasis after nCRT. Overall survival (P < 0.001) and disease-free survival (P < 0.001) were significantly worse in patients with LLN metastasis, which was, however, not an independent risk factor for survival after eliminating confounders. Multivariate prognostic analysis of 40-patient subset with pathological LLN metastasis showed that distant metastasis, metastasis beyond the obturator or internal iliac region, and ≥2 LLN metastasis were independent predictors of poor overall survival.ConclusionsSelective LLN dissection after nCRT is safe and feasible with acceptable perioperative outcomes. Patients with a post-nCRT LLN short diameter ≥7 mm or poor/mucinous/signet adenocarcinoma should receive supplementary LLN dissection after nCRT. However, patients with distant metastasis, metastasis beyond the obturator or internal iliac region, and involvement of ≥2 LLN may not benefit from LLN dissection, and LLN dissection should be carefully considered in such patients.

Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body’s primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.