Search

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic in China is ongoing. Some studies have shown that the incidence of respiratory and intestinal infectious diseases in 2020 decreased significantly compared with previous years. Interrupted time series (ITS) is a time series analysis method that evaluates the impact of intervention measures on outcomes and can control the original regression trend of outcomes before and after the intervention. This study aimed to analyse the impact of COVID-19 on the incidence rate of notifiable communicable diseases using ITS in China. Methods National data on the incidence rate of communicable diseases in 2009–2021 were obtained from the National Health Commission website. Interrupted time series analysis using autoregressive integrated moving average (ARIMA) models was used to analyse the changes in the incidence rate of infectious diseases before and after the COVID-19 epidemic. Results There was a significant short-term decline in the incidence rates of respiratory infectious diseases and enteric infectious diseases (step values of -29.828 and − 8.237, respectively), which remained at a low level for a long time after the decline. There was a short-term decline in the incidence rates of blood-borne and sexually transmitted infectious diseases (step = -3.638), which tended to recover to previous levels in the long term (ramp = 0.172). There was no significant change in the incidence rate of natural focus diseases or arboviral diseases before and after the epidemic. Conclusion The COVID-19 epidemic had strong short-term and long-term effects on respiratory and intestinal infectious diseases and short-term control effects on blood-borne and sexually transmitted infectious diseases. Our methods for the prevention and control of COVID-19 can be used for the prevention and control of other notifiable communicable diseases, especially respiratory and intestinal infectious diseases.

BackgroundLead and manganese are heavy metal pollutants widely existing in the environment, which can accumulate in the human body through the food chain, exert neurotoxicity, and cause neurodegenerative disorders. Especially in early childhood, the developing blood-brain barrier and nervous system are highly susceptible to environmental chemical pollutants. Most of the previous studies focused on the toxic effects of single heavy metal such as lead or manganese, while the studies on combined toxic effect are still scarce, and involved mechanisms are still unclear. c-Jun N-terminal kinase (JNK) is involved in neuronal development and regeneration, and some studies have found that JNK is involved in lead or manganese induced neurotoxicity. Its role in the toxicity of combined lead and manganese is unknown. ObjectiveTo understand the neurodevelopmental toxicity mechanism and to observe changes of JNK expression in zebrafish induced by combined lead and manganese exposure at environmentlly low concentrations. MethodsZebrafish embryos within 2 h post fertilization (hpf) were divided into four groups: control group, lead exposure group (0.1 mg·L−1 lead acetate), manganese exposure group (0.3 mg·L−1 manganous chloride), and lead-manganese combined exposure group (0.1 mg·L−1 lead acetate +0.3 mg·L−1 manganous chloride) and exposed to lead or/and manganese at designed levels for 7 d. Spontaneous movements and motor locomotion were observed, and mortality rate were calculated. The changes of JNK mRNA expression in zebrafish were evaluated. ResultsThe experimental results showed that no significant effect of lead or/and manganese on spontaneous movements and mortality rate was found in zebrafish compared with the control group (P＞0.05). The results of locomotion analysis showed that compared with the control group, the activity counts and activity distance of zebrafish in the manganese exposure group were slightly increased (P＜0.01); the activity counts and activity distance of zebrafish in the lead exposure group were reduced by 50% and those in the lead-manganese exposure group were reduced by 80% (P＜0.01). Compared with the lead exposure group, the activity counts and activity distance of zebrafish in the lead-manganese combined exposure group decreased significantly by 60% (P＜0.05). The real-time quantitative PCR results showed that the JNK mRNA expression level was significantly increased in the lead-manganese combined exposure group compared with the control group(P＜0.01). ConclusionLead exposure combined with manganese exposure at environmentlly low concentration can induce neurodevelopmental toxicity to zebrafish. JNK may be involved in neurodevelopmental toxicity induced by the combined exposure to lead and manganese.

Oncolytic viruses (OVs) are emerging cancer therapeutics that offer a multifaceted therapeutic platform for the benefits of replicating and lysing tumor cells, being engineered to express transgenes, modulating the tumor microenvironment (TME), and having a tolerable safety profile that does not overlap with other cancer therapeutics. The mechanism of OVs combined with other antitumor agents is based on immune-mediated attack resistance and might benefit patients who fail to achieve durable responses after immune checkpoint inhibitor (ICI) treatment. In this Review, we summarize data on the OV mechanism and limitations of monotherapy, which are currently in the process of combination partner development, especially with ICIs. We discuss some of the hurdles that have limited the preclinical and clinical development of OVs. We also describe the available data and provide guidance for optimizing OVs in clinical practice, as well as a summary of approved and promising novel OVs with clinical indications.

AbstractBackground Acute pancreatitis (AP) is associated with a high incidence of acute kidney injury (AKI). This study aimed to develop a nomogram for predicting the early onset of AKI in AP patients admitted to the intensive care unit.Method Clinical data for 799 patients diagnosed with AP were extracted from the Medical Information Mart for Intensive Care IV database. Eligible AP patients were randomly divided into training and validation cohorts. The independent prognostic factors for the early development of AKI in AP patients were determined using the all-subsets regression method and multivariate logistic regression. A nomogram was constructed for predicting the early occurrence of AKI in AP patients. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA).Results Seven independent prognostic factors were identified as predictive factors for early onset AKI in AP patients. The AUC of the nomogram in the training and validation cohorts were 0.795 (95% CI, 0.758–0.832) and 0.772 (95% CI, 0.711–0.832), respectively. The AUC of the nomogram was higher compared with that of the BISAP, Ranson, APACHE II scores. Further, the calibration curve revealed that the predicted outcome was in agreement with the actual observations. Finally, the DCA curves showed that the nomogram had a good clinical applicability value.Conclusion The constructed nomogram showed a good predictive ability for the early occurrence of AKI in AP patients.

The use of titanium dioxide in the degradation of water pollutants encounters several challenges, including particle agglomeration leading to a reduction in its specific surface area and a high rate of photogenerated electron-hole recombination, resulting in a lower quantum efficiency. Therefore, in this work, we first employed sepiolite to load titanium dioxide, mitigating particle agglomeration. Building upon this, tin dioxide was coupled with it to enhance the photogenerated charge separation. The SnO2/TiO2/sepiolite photocatalytic composites were synthesized using the sol–gel method at 450 ℃. The resulting composites underwent thorough characterization encompassing phase composition, morphology, chemical valence states, specific surface area, optical properties, and photocatalytic activity. The outcomes demonstrate an augmentation in the specific surface area of TiO2/Sep composites following the sepiolite (Sep) loading. Among these, the TiO2/Sep composite (with a Sep: TiO2 mass ratio of 10 %) exhibited the most favorable photocatalytic performance, displaying a first-order reaction rate constant of 0.010 min−1, surpassing that of pure TiO2 by a factor of 2.0. The introduction of SnO2 expedited the migration of photogenerated charge across interfaces, curbing the recombination of photogenerated pairs, thus enhancing quantum efficiency. In light of the presence of sepiolite, the addition of SnO2 further amplified the photocatalytic performance. Optimal results were achieved when the molar ratio of SnO2:TiO2 was set at 1:4, leading to the highest photocatalytic efficiency observed in the SnO2/TiO2/Sep composite. This composite exhibited a first-order reaction rate constant of 0.027 min−1, marking a notable 2.7-fold increase compared to the TiO2/Sep counterpart. The investigation of band potentials, charge transfer pathways, and the photocatalytic mechanism within SnO2/TiO2/Sep composite materials was conducted through a comprehensive analysis involving electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS) valence band spectroscopy, electron paramagnetic resonance spectra (EPR) and active radical experiments.

Objectives To explore the prevalence and associated factors of COVID-19 anxiety in patients with late-life depression (LLD) during the adjustment of epidemic prevention policies in China.Design Cross-sectional study.Setting The data analysed in this study were collected from seven regions in China between November 2022 and January 2023.Participants A total of 1205 patients with LLD (aged 60–78 years) participated in the survey. They completed a social demographic assessment and the Chinese version of the five-point Coronavirus Anxiety Scale (CAS).Primary outcome measures The primary outcome was the anxiety level of the participants. Patients were categorised into two groups based on their anxiety levels, one with anxiety and one without, according to CAS scores.Results The prevalence of COVID-19 anxiety in depressed older adults was 47.3%. Regression analysis revealed that the average COVID-19 anxiety score was significantly higher among females (AOR: 2.177, 95% CI 1.201 to 3.947), widowed individuals (AOR: 3.015, 95% CI 1.379 to 6.591), patients residing at a distance from healthcare facilities (AOR: 3.765, 95% CI 1.906 to 7.438), and those who frequently experienced worry (AOR: 1.984, 95% CI 1.111 to 3.543). Conversely, the anxiety score was significantly lower among divorced individuals (AOR: 0.491, 95% CI 0.245 to 0.988), those aged 70 years and above (AOR: 0.117, 95% CI 0.064 to 0.213), patients without difficulty obtaining medication (AOR: 0.027, 95% CI 0.007 to 0.097), those living with family members (AOR: 0.080, 95% CI 0.022 to 0.282) or in nursing homes compared with those living alone (AOR: 0.019, 95% CI 0.004 to 0.087).Conclusion Women with LLD who are widowed, live far from healthcare facilities, and are prone to excessive worry are more likely to experience anxiety. It is advisable to implement appropriate preventive measures and provide psychosocial support programmes for this vulnerable group during the COVID-19 pandemic.

BackgroundThe frequency of nipple-sparing mastectomy (NSM) surgery is presently increasing. Nonetheless, there is a paucity of long-term prognosis data on NSM. This study compared the long-standing prognosis of NSM in relation to breast-conserving surgery (BCS).MethodsPopulation-level data for 438,588 female breast cancer patients treated with NSM or BCS and postoperative radiation from 2000 to 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER) database; 321 patients from the Second Xiangya Hospital of Central South University were also included. Propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables to make valid comparisons. The Kaplan–Meier analysis, log-rank test, and Cox regression were applied to analyze the data.ResultsThere were no significant differences in long-term survival rates between patients who underwent NSM and those who underwent BCS+radiotherapy (BCS+RT), as indicated by the lack of significant differences in overall survival (OS) (p = 0.566) and breast cancer-specific survival (BCSS) (p = 0.431). Cox regression indicated that NSM and BCS+RT had comparable prognostic values (p = 0.286) after adjusting for other clinicopathological characteristics. For OS and BCSS, subgroup analysis showed that the majority of patients achieved an analogous prognosis whether they underwent NSM or BCS. The groups had comparable recurrence-free survival (RFS), with no significant difference found (p = 0.873).ConclusionsThis study offers valuable insights into the long-term safety and comparative effectiveness of NSM and BCS in the treatment of breast cancer. These findings can assist clinicians in making informed decisions on a case-by-case basis.

We study the existence and wave-speed management of nonlinear localized waves in an inhomogeneous birefringent nonlinear dispersive medium in the presence of external potential. The coupled nonlinear Schrödinger equation with varying coefficients which can be applied to model the interaction among the modes in nonlinear optics and in Bose–Einstein condensation is considered. By means of a complex transformation, we derive new types of periodic nonlinear waves for the present coupled system which are expressed in terms of Jacobi elliptic functions. Novel soliton pulse solutions including bright-dipole and bright–dark solutions are identified in the long-wave limit of these periodic solutions. As an application of these soliton pulses, we discuss their wave-speed management for the different choices of dispersion parameter. The results show that the varied dispersion parameter can be used to control effectively the wave speed of propagating localized waves.

Abstract Objective To understand the prevalence of hypertension and hyperlipidaemia as well as the current status of glycaemic control and its influencing factors among type 2 diabetes mellitus patients in the community in South China, and to provide recommendations for the prevention and control of diabetes. Methods Questionnaires, physical examinations and laboratory tests were conducted on patients with type 2 diabetes mellitus who participated in the National Basic Public Health Service Programme in Guangzhou in 2020. The chi-square test, t-test and multi-factor unconditional logistic regression analysis were performed using R 4.1.2 software. Result Among 127,423 type 2 diabetic patients in Guangzhou, 57,695 achieved glycemic control standards, with a glycemic control rate of 45.28%.In this study, the proportion of T2DM patients with hypertension and hyperlipidaemia together was 27.79%, The percentage of T2DM patients with hypertension alone and hyperlipidaemia alone was 28.34% and 20.53% respectively, and the rate of no complications was 23.34%. There was a statistically significant difference in the rate of glycaemic control between the different disease combination states (P

The innovation and regulatory coordination of digital currency is an important proposition in the new era of Fintech. There is increasing competition between traditional currencies and new digital currencies, so a spontaneous game model of currencies is analyzed. By introducing the role of financial coordination, this paper revises the evolutionary game model of digital currency innovation, and analyzes their competition strategies through case and simulation. The results show that: first, the dominant result of digital currency spontaneous game is that both parties tend to digital cooperation strategy. Second, with the introduction of financial regulation, the dominant result of digital currency tripartite evolutionary game is that financial institutions tend to participate in coordination and both currency parties tend to cooperate. Third, the choice strategy of currency is more sensitive to the changes of willingness to participate in cooperation, cooperation costs and cooperation benefits of financial coordination. The selection strategy of financial coordination institutions for digital currency is more influenced by changes in cooperation costs and incentive return in the process of participating in cooperation.

Abstract Background Germline mutations in the APC gene located on chromosome 5q 21–22 can lead to familial adenomatous polyposis (FAP) and the development of colorectal cancer (CRC) if left untreated. As a rare extracolonic manifestation, thyroid cancer is diagnosed in about 2.6% of FAP patients. The genotype–phenotype correlation in FAP patients with thyroid cancer remains unclear. Case presentation We present a 20-year-old female of FAP with thyroid cancer as the initial manifestation. The patient was asymptomatic and developed colon cancer liver metastases 2 years after the diagnosis of thyroid cancer. The patient underwent multiple surgical treatments in several organs, and regular colonoscopy with endoscopic polypectomy was performed. Genetic testing demonstrated the c.2929delG (p.Gly977Valfs*3) variant in exon 15 of the APC gene. This represents a previously undescribed APC mutation. This mutation causes loss of multiple structures on the APC gene including the 20-amino acid repeats, the EB1 binding domain, and the HDLG binding site, which may be pathogenic through β-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation. Conclusions We report a de novo FAP case with thyroid cancer presenting atypically aggressive features harboring a novel APC mutation and review APC germline mutations in patients with FAP-associated thyroid cancer.

Abstract Objective The KEYNOTE‐590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first‐line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. Methods A Markov model was used to simulate 10‐year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD‐L1 positive score (CPS ≥10) and any PD‐L1 expression groups, respectively. We estimated total costs, quality‐adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. Results The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD‐L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. Conclusions Evidence suggests that first‐line pembrolizumab in combination with chemotherapy is not a cost‐effective option for advanced esophageal cancer in the US, regardless of PD‐L1 expression status.

Objective This study was conducted to determine the optimal dose of novel iron amino acid complexes (Fe-Lys-Glu) by measuring laying performance, egg quality, egg iron (Fe) concentrations, and blood biochemical parameters in laying hens. Methods A total of 1,260 18-week-old healthy Beijing White laying hens were randomly divided into 7 groups with 12 replicates of 15 birds each. After a 2-wk acclimation to the basal diet, hens were fed diets supplemented with 0 (negative control, the analyzed innate iron content was 75.06 mg/kg), 15, 30, 45, 60, and 75 mg Fe/kg as Fe-Lys-Glu or 45 mg Fe/kg from FeSO4 (positive control) for 24 wk. Results Results showed that compared with the negative and positive control groups, dietary supplementation with 30 to 75 mg Fe/kg from Fe-Lys-Glu significantly (linear and quadratic, p

Background: To explore the risk factors for early pregnancy loss and to study the relationship between early pregnancy loss and intrauterine adhesion (IUA) confirmed by hysteroscopy. Methods: A retrospective study was conducted on 226 early pregnancy loss and 51 early pregnancy patients who received medical management combined with hysteroscopy at a regional institution from March 2020 to February 2021. The uterine cavity’s shape was evaluated by hysteroscopy 6 hours after treatment with medicine. Risk factors included maternal age, gestational weeks, gravidity, parity, number of prior early pregnancy losses, number of prior induced abortions, mean sac diameter (MSD) and IUA. Results: Our results showed that the prevalence of IUA increased significantly in early pregnancy loss cases (31.42%) compared with early pregnancy cases (9.8%) (p < 0.01). Multivariate logistic regression analysis showed that maternal age (odds ratio (OR): 1.195, 95% confidence interval (95% CI): 1.077–1.326), gestational weeks (OR: 2.919, 95% CI: 2.028–4.201) and IUA (OR: 8.631, 95% CI: 2.455–30.336) were positively associated with early pregnancy loss, while MSD (OR: 0.943, 95% CI: 0.899–0.990) and parity (OR: 0.194, 95% CI: 0.088–0.428) were inversely associated with early pregnancy loss. Conclusions: Maternal age, gestational weeks and, IUA were the risk factors for early pregnancy loss. Special attention is to be given to cases of combined IUA when managing early pregnancy loss.

IntroductionAs a developing country with the largest older adult population in the world, strengthening the research on falls among the older adults is undoubtedly an urgent item in China. This study aimed to explore the prevalence and risk factors associated with falls and injury from falls among community-dwelling older adults in Guangzhou, China, particularly focusing on their associations with chronic diseases.MethodsA total of 1,629 participants aged 65 years and above were selected from 11 counties in Guangzhou by the multi-stage stratified random sampling method in 2021. Socio-demographic characteristics, health and lifestyle factors, the status of falls, and injury from falls were measured by structured questionnaires through face-to-face interviews. Chi-square tests and logistic regression analysis were used to identify factors associated with falls and injury from falls. Chord diagrams were used to explore their associations with chronic diseases.ResultsA total of 251 participants (15.41%, 95% CI: 13.98%−17.25%) reported falls, and 162 participants (9.46%, 95% CI:7.72%−11.55%) indicated an injury from falls. Logistic regression analysis showed the results as follows: female patients (adjusted OR = 1.721, 95% CI: 1.681–1.761) aged ≥80 years (1.910, 1.847–1.975), unemployed (1.226, 1.171–1.284), uninsured (1.555, 1.448–1.671), average monthly household income of 2,001–4,000 CNY (1.878, 1.827–1.930), number of services provided by the community health center ≥13 times per year (1.428, 1.383–1.475), illness within 2 weeks (1.633, 1.595–1.672), high-intensity physical activity (2.254, 2.191–2.32), sedentary (1.094, 1.070–1.117), and number of chronic disease illnesses ≥3 (1.930, 1.870–1.993). Meanwhile, those risk factors were also associated with injury from falls. The older adults with medium-intensity physical activity were at lower risk (0.721, 0.705–0.737) of falls and higher risk (1.086, 1.057–1.117) of being injured from falls. Chord diagrams showed the correlations between chronic diseases and falls and injury from falls among community-dwelling older adults in Guangzhou, China.ConclusionThe high prevalence of falls is found among community-dwelling older adults in Guangzhou, China, which is related to multiple factors such as demographic variables, lifestyle, and health status, especially for chronic diseases. Therefore, targeted interventions should be developed and implemented urgently.

Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194–5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.

Exposure to lead (Pb) and manganese (Mn) during early life influences neurodevelopment and increases the risk of neurodegenerative disorders. However, the level of developmental neurotoxicity due to combined exposure to the two metals remains unclear. Although the microbiota plays an essential part in the development of the nervous system via the gut–brain axis, there is a paucity of information regarding the interactions between exposure to Pb and Mn, the destruction of the microbiome, and neurodevelopmental impacts. To fill in this knowledge gap, we investigated the developmental neurotoxicity and effects on the microbiota of Pb (0.05 mg·L−1) alone and in combination with Mn (0.3 mg·L−1) in zebrafish larvae. Our results revealed that combined exposure precipitated higher malformation rates and lower locomotor activity levels than exposure to either Pb or Mn alone. Additionally, when we separated the combined exposure group from the other groups by applying unsupervised principal coordinates analysis (PCoA) and linear discriminant analysis (LEfSe) of microflora sequencing results, we observed extensive alterations in microbial abundances under combined-exposure conditions. Functional prediction analysis showed that combined exposure contributed to altered amino acid and lipid metabolism, and also that combined exposure to Pb and Mn reflected the greatest number of differentially activated biological pathways compared to the other three groups. ATP-binding cassette G (ABCG) genes and genes related to serotonin signaling and metabolism were altered following combined Pb and Mn exposure and exhibited disparate trends vis-à-vis Pb or Mn exposure alone. According to the results, the combined exposure to Pb and Mn led to more severe effects on both zebrafish locomotor activity and gut microbial composition. We suggest that the microbiota contributes to the combined neurotoxicity by increasing ABCG5 and ABCG8 gene expression.

Accumulating evidence indicates that m 6 A methyltransferase 3 (METTL3) plays a pivotal role in different malignancies including melanoma. However, the function and underlying mechanisms by which METTL3 contributes to the tumorigenesis of melanoma remain undocumented. The association of METTL3 and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) with clinicopathological characteristics and prognosis in patients with melanoma was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, and The Cancer Genome Atlas data sets. The role of METTL3 in melanoma cells was assessed by in vitro and in vivo experiments. The m 6 A dot blot, methylated RNA immunoprecipitation (MeRIP), and RT-qPCR were used to verify METTL3-mediated m 6 A modification of lncRNA SNHG3. The effect of METTL3 on lncRNA SNHG3 was determined by luciferase gene reporter assay, RT-qPCR, and Western blotting. We found that METTL3 was upregulated in melanoma tissue samples and associated with poor survival in patients with melanoma. Knockdown of METTL3 suppressed the growth and invasion of melanoma cells in vitro and in vivo , whereas restored expression of METTL3 promoted these effects. Mechanistic investigations showed that knockdown of METTL3 reduced SNHG3 m 6 A levels and its messenger ribonucleic acid (mRNA) expression levels. SNHG3 could act as a sponge of microRNA (miR)-330-5p to upregulate the expression of CCHC-type zinc finger nucleic acid binding protein (CNBP). SNHG3 overexpression reversed METTL3-knockdown-caused antitumor effects, miR-330-5p upregulation and CNBP downregulation. SNHG3 had a positive correlation with METTL3 expression but a negative correlation with miR-330-5p expression in melanoma tissue samples. In conclusion, our findings demonstrated that METTL3-mediated m 6 A modification of lncRNA SNHG3 promoted the growth and invasion of melanoma cells by regulating the miR-330-5p/CNBP axis.

BackgroundTreating triple-negative breast cancer (TNBC) is a difficult landscape owing to its short survival times and high risk of metastasis and recurrence among patients. Although involved in tumor invasion and metastasis, the mechanism of action of intercellular adhesion molecule 1 (ICAM1), a trans-membrane glycoprotein, in TNBC is ambiguous.MethodsWe examined ICAM1’s role in TNBC, focusing on its expression, cell survival, mutation, and tumor immunity. Then, a risk score model was created utilizing co-expressed genes associated with ICAM1. According to their respective risk scores, we divided patients into high- and low-risk groups. Immune function, drug susceptibility differences, and somatic variants were analyzed in the high-and low-risk groups. And we used the CMap database to predict potential medications. Then, TNBC cells with low expression of ICAM-1 were co-cultured with PMA-treated THP-1 cells and CD8 T cells. In addition, We detected the expression of PD-1 and CTLA4 of low ICAM-1 expressing TNBC cells when they were cocultured with CD8 T cells.ResultsICAM1 was found to be involved in leukocyte cell adhesion, motility, and immune activation. Patients with low-ICAM1 group had shorter disease-free survival (DFS) than those with high-ICAM1 group. The group with elevated levels of ICAM1 exhibited significantly increased levels of T-cell regulation, quiescence in natural killer (NK) cells, and M1 macrophage. ICAM1 expression was correlated with immune checkpoint drugs. The prognostic ability of the risk score model was found to be superior to that of individual genes. Patients categorized as high-risk exhibited elevated clinical stages, showed higher M1 macrophage numbers, and were able to benefit better from immunotherapy. Individuals belonging to the high-risk group exhibit significantly elevated mutation rates in TP53, TTN, and SYNE1 genes, along with increased TMB and PD-L1 levels and decreased TIDE scores. These findings suggest that immunotherapy may be advantageous for the high-risk group. Furthermore, low expression of ICAM1 was found to promote polarization to M2 macrophages along with T-cell exhaustion.ConclusionIn conclusion, Low ICAM1 expression may be related to immune escape, leading to poor treatment response and a worse prognosis.

Abstract Background With the popularity of medical aesthetic programs, some female adults who will or are undergoing orthodontic treatment often wonder whether orthodontic treatment has adverse effects on the nasolabial folds (NLFs). The aims of the study were to investigate any potential changes in the NLFs and associated peripheral soft tissues after orthodontic treatment of female adults. Methods This study compared changes in the NLFs and peripheral soft tissues in female adults undergoing orthodontic treatment using the 3dMD Face system (3dMD, Atlanta, Ga). A total of 52 adult female patient cases (24 teeth extraction, 28 non-teeth extraction) were included to evaluate the effects of different orthodontic treatment regimens on the NLFs and peripheral soft tissues. Results In the NLFs area, the landmarks of the extraction group were all significantly negatively changed (P

Abstract Objective This study aims to investigate the correlation of long non-coding RNA HOX transcript antisense RNA (lncRNA HOTAIR) with the PTEN/PI3K/AKT pathway and clinical-related indicators in osteoarthritis (OA) and determine the effect of baicalin intervention. Methods The levels of clinical lipid metabolism indexes and immune-inflammatory indexes in OA patients and normal controls was detected. OA chondrocytes (OA-CHs) were induced with peripheral blood mononuclear cells (PBMCs), followed by baicalin treatment (50 ug/mL). RT-qPCR was performed to measure lncRNA HOTAIR expression. The levels of inflammatory cytokines and adiponectin were detected using ELISA kits. CCK-8 assay was used to assess the viability of CHs. The related protein expression was measured using Western blot analysis. Results LncRNA HOTAIR might act as a biomarker of OA in vivo. LncRNA HOTAIR was positively correlated with TC, hs-CRP, IgA, TNF-α, and VAS score. Overexpression of lncRNA HOTAIR in vitro inhibited cell proliferation, reduced IL-10 and PTEN expression, but augmented TNF-α, p-PI3K, and p-AKT proteins in OA-CHs stimulated by OA-PBMCs. The changes of above indexes were also observed in OA-CHs stimulated by OA-PBMCs treated with si-lncRNA HOTAIR or baicalin, implying the synergistic effects of baicalin and lncRNA HOTAIR silencing on OA. Conclusions Conclusively, lncRNA HOTAIR was highly expressed in OA-CHs, which facilitated OA inflammatory responses by orchestrating inflammatory cytokines and the PTEN/PI3K/AKT pathway. Baicalin exerted therapeutic effects by inhibiting the expression of lncRNA HOTAIR, decreasing the protein levels of p-PI3K and p-AKT, and increasing the protein levels of PTEN, APN, and ADIPOR1.

Abstract Polygonum chinense Linn. (Polygonum chinense L.) is one of the main raw materials of Chinese patent medicines such as Guangdong herbal tea. The increasing antibiotic resistance of S. aureus and the biofilm poses a serious health threat to humans, and there is an urgent need to provide new antimicrobial agents. As a traditional Chinese medicine, the antibacterial effect of Polygonum chinense L. has been reported, but the antibacterial mechanism of Polygonum chinense L.aqueous extract and its effect on biofilm have not been studied in great detail, which hinders its application as an effective antibacterial agent. In this study, the mechanism of action of Polygonum chinense L.aqueous extract on Staphylococcus aureus (S. aureus) and its biofilm was mainly evaluated by morphological observation, flow cytometry and laser confocal experiments. Our findings demonstrate that Polygonum chinense L.aqueous extract has a significant bacteriostatic effect on S. aureus. The result of growth curve exhibits that Polygonum chinense L.aqueous extract presents a significant inhibitory effect against S. aureus. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) reveals that Polygonum chinense L.aqueous extract exerts a potent destruction of the cell wall of S. aureus and a significant inhibitory effect on the formation of S. aureus biofilm. In addition, flow cytometry showed the ability of Polygonum chinense L.aqueous extract to promote apoptosis by disrupting cell membranes of S. aureus. Notably, confocal laser scanning microscopy (CLSM) images illustrated the ability of Polygonum chinense L.aqueous to inhibit the formation of S. aureus biofilms in a dose-dependent manner. These results suggested that Polygonum chinense L.aqueous is a promising alternative antibacterial and anti-biofilm agent for combating infections caused by planktonic and biofilm cells of S. aureus.

Introduction Virtual home visits may improve chronic disease management. However, whether they are suitable for peritoneal dialysis (PD) patients has not yet been fully investigated. This study aimed to compare the agreement and acceptance of virtual home visits and in-person home visits in PD patients.Methods This was a paired, single center, noninferiority trial. Participants received a virtual home visit and an in-person home visit simultaneously. A home visit checklist was built for standardization visits. The content was divided into three parts: domestic habits (57 items), bag exchange procedures (56 items), and exit site care (53 items). Satisfaction questionnaires for both patients and nurses were designed to assess attitudes toward home visits and socioeconomic effects.Results A total of 30 PD patients were enrolled in a single center. The information collected from virtual home visits and in-person home visits was found to be highly consistent. The perfect agreement was found in 52/57, 49/56, and 44/53 items (Cohen's kappa 0.81–1.00), substantial agreement in 4/57, 7/56, and 8/53 items (Cohen's kappa 0.61–0.80). Patients reported almost identical satisfaction for virtual home visits and in-person home visits (Z = 0.39, p = 0.70). PD nurses reported similar feasibility and patient cooperation for the two visit types (Z = 0.99, p = 0.33; Z = 1.65, p = 0.10, respectively). In addition, virtual home visits were found to be more cost-effective than in-person home visits.Conclusions Virtual home visits information collection was similar to in-person home visits in PD. There were no differences in participant satisfaction and feasibility between the two visit types.

Abstract Background Plants are continuously challenged with biotic stress from environmental pathogens, and precise regulation of defense responses is critical for plant survival. Defense systems require considerable amounts of energy and resources, impairing plant growth, and plant hormones controlling transcriptional regulation play essential roles in establishing the appropriate balance between defense response to pathogens and growth. Chromatin regulators modulating gene transcription are broadly involved in regulating stress-responsive genes. However, which chromatin factors are involved in coordinating hormone signaling and immune responses in plants, and their functional mechanisms, remains unclear. Here, we identified a role of bromodomain-containing protein GTE4 in negatively regulating defense responses in Arabidopsis thaliana. Results GTE4 mainly functions as activator of gene expression upon infection with Pseudomonas syringe. Genome-wide profiling of GTE4 occupancy shows that GTE4 tends to bind to active genes, including ribosome biogenesis related genes and maintains their high expression levels during pathogen infection. However, GTE4 is also able to repress gene expression. GTE4 binds to and represses jasmonate biosynthesis gene OPR3. Disruption of GTE4 results in overaccumulation of jasmonic acid (JA) and enhanced JA-responsive gene expression. Unexpectedly, over-accumulated JA content in gte4 mutant is coupled with downregulation of JA-mediated immune defense genes and upregulation of salicylic acid (SA)-mediated immune defense genes, and enhanced resistance to Pseudomonas, likely through a noncanonical pathway. Conclusions Overall, we identified a new role of the chromatin factor GTE4 as negative regulator of plant immune response through inhibition of JA biosynthesis, which in turn noncanonically activates the defense system against Pseudomonas. These findings provide new knowledge of chromatic regulation of plant hormone signaling during defense responses.

The damage of proximal tubular epithelial cells (PTECs) is considered a central event in the pathogenesis of chronic kidney disease (CKD) and deregulated repair processes of PTECs result in epithelial–mesenchymal transition (EMT), which in turn aggravates tubular injury and kidney fibrosis. In this study, we firstly revealed that the reduction of TTC36 is associated with unilateral ureteral obstruction (UUO)-induced CKD; besides, ablation of TTC36 attenuated tubular injury and subsequent EMT in UUO-treated mice kidneys. Consistently, TTC36 overexpression promoted EMT in TGF-β1-induced HK2 cells. Moreover, TTC36 elevated the protein expression of CEBPB, which was involved in the regulation of TGF-β/SMAD3 signaling, and augmented SMAD3 signaling and downstream genetic response were reduced by CEBPB silencing. Collectively, our results uncovered that TTC36 deficiency plays a protective role in tubular injury and renal fibrosis triggered by UUO; further, TTC36 overexpression exacerbated TGF-β/SMAD3 signaling via elevating the stability of SMAD3 and CEBPB, suggesting that TTC36 inhibition may be a potential strategy in the therapy of obstructive nephropathy.

Abstract Background Age estimation from panoramic radiographs is a fundamental task in forensic sciences. Previous age assessment studies mainly focused on juvenile rather than elderly populations (> 25 years old). Most proposed studies were statistical or scoring-based, requiring wet-lab experiments and professional skills, and suffering from low reliability. Result Based on Soft Stagewise Regression Network (SSR-Net), we developed DENSEN to estimate the chronological age for both juvenile and older adults, based on their orthopantomograms (OPTs, also known as orthopantomographs, pantomograms, or panoramic radiographs). We collected 1903 clinical panoramic radiographs of individuals between 3 and 85 years old to train and validate the model. We evaluated the model by the mean absolute error (MAE) between the estimated age and ground truth. For different age groups, 3–11 (children), 12–18 (teens), 19–25 (young adults), and 25+ (adults), DENSEN produced MAEs as 0.6885, 0.7615, 1.3502, and 2.8770, respectively. Our results imply that the model works in situations where genders are unknown. Moreover, DENSEN has lower errors for the adult group (> 25 years) than other methods. The proposed model is memory compact, consuming about 1.0 MB of memory overhead. Conclusions We introduced a novel deep learning approach DENSEN to estimate a subject’s age from a panoramic radiograph for the first time. Our approach required less laboratory work compared with existing methods. The package we developed is an open-source tool and applies to all different age groups.

Laboratory spectroscopic and X-ray diffraction analyses on the Chang’E-5 lunar soil samples have demonstrated that the spectral features of lunar late-stage mare basalts are representative of iron-rich high-Ca pyroxene rather than olivine.

Abstract Acute kidney injury (AKI) is in high prevalence in the world. However, the therapeutic strategies for AKI are still in mystery. Studies have shown to improve autophagy and lysosomal function could inhibit AKI. But their modulators need to be explored in detail. Annexin A2 (ANXA2) is a phospholipid-binding protein involving in organelle membrane integrity function, suggesting its important role in autophagy and lysosome homeostasis. It implicates ANXA2 potentially protects against AKI. However, this has not been elucidated. Herein, we found that ANXA2 is increased in renal tubules in cisplatin-induced AKI mice. Ectopic expression of ANXA2 improved lysosomal functions and enhanced autophagic flux, further protecting against renal tubular cell apoptosis and kidney injury. Conversely, knockdown of ANXA2 inhibited lysosomal function and autophagy, which aggravated the progression of AKI. Transcriptome sequencing revealed β-catenin signaling is highly responsible for this process. In vitro, we found ANXA2 induced β-catenin activation, further triggering T-cell factor-4 (TCF4)-induced transcription factor EB (TFEB). Furthermore, TFEB promoted lysosome biogenesis to enhance autophagic flux, resulting in the alleviation of AKI. Our new findings underline ANXA2 is a new therapeutic potential for AKI through modulating autophagy and lysosomal function. The underlying mechanism is associated with its inductive effects on β-catenin/TFEB pathway.

To address the low precision of pairwise registration method based on the deep learning and the time-consuming nature of traditional registration algorithm, this paper presents a method of unsupervised end-to-end groupwise registration based on variational inference, as well as a registration framework based on normalized cross correlation (NCC) and prior knowledge. The framework can warp all images in the group into a common space and effectively control the deformation field of the regularization, and it doesn't need a real deformation field or a reference image. The estimation of deformation field by this method can be modeled as a probability generation model and solved by variational inference. Then unsupervised training is implemented with the help of spatial transformer network and loss function. The registration results of 3D brain magnetic resonance image from the public data set LPBA40 show that: compared with the baseline method, the proposed method has better Dice score, less running time, better diffeomorphisms domain, and is robust to noise.

Abstract Background A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. Methods This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). Results Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P

Abstract Background To investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT). Methods We retrospectively analyzed 192 naive LACC (stage IIB–IVA) patients who underwent intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy in Xiangya Hospital from January 2014 to June 2017. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to evaluate the effect of various factors on overall survival (OS) and progression-free survival (PFS). The nomogram and calibration curves were generated on the basis of survival analysis. Results The median follow-up time was 39.5 months. There-year rates of OS and PFS were 89.1% and 82.8%. LACC patients with non-squamous cell carcinoma [NSCC, including adenocarcinoma or adenosquamous carcinoma (AC/ASC)], advanced stage (IIIA-IVA), initially positive lymph node (pelvic or para-aortic lymph node, PLN/PALN), and a lower pretreatment hemoglobin (HGB) level (

Abstract Objective Fear aura has traditionally been considered relevant to epileptic discharges from mesial temporal areas, and few studies have investigated its effect on surgical outcome in drug‐resistant epilepsy. We aim to assess the localizing and lateralizing value as well as prognostic significance of fear aura in patients with focal epilepsy. Methods The occurrence of fear aura in relation to epileptogenic origin and its association with postoperative outcome were analyzed in 146 consecutive patients undergoing resective surgery for intractable epilepsy. Results Ninety‐four (64.4%) patients reported auras, and 31 (21.2%) reported fear aura in their seizures. One hundred ten (75.3%) patients had an Engel class I outcome until last follow‐up, of whom 24 experienced fear aura preoperatively. Fear aura appeared more frequently during temporal and frontal lobe seizures, but did not lateralize the seizure onset zone. There were no significant baseline differences between patients with and without fear aura. No correlation was found between postoperative outcome and the presence of auras. Occurrence of fear aura failed to show predictive value in surgical outcome whether in pooled or subgroup analysis. Interpretation This study advances our understanding of the origin of fear aura, and is helpful for presurgical evaluation and outcome prediction. Without lateralizing value, fear aura is more commonly seen with temporal or frontal origin. When taken as a whole, auras do not have a significant impact on seizure outcome in focal epilepsy. Patients with fear aura are no more likely to become seizure‐free than those without fear aura.

Abstract Background Currently, the effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) remains unclear. This study aims to investigate the relationship between changes in skeletal muscle and postoperative complications, survival and tumor response in patients with LA-GIST during neoadjuvant therapy with imatinib. Methods We retrospectively analyzed pre- and post-treatment computed tomography images of 57 GIST patients who underwent radical surgery after neoadjuvant therapy with imatinib from January 2013 to March 2019. Skeletal muscle index (SMI) was measured at the L3 vertebral level in all patients. A cut-off value (SMI

AimTo evaluate the performances of D-dimer, prothrombin time (PT), and red blood cell distribution width (RDW) for the diagnosis of coronary artery lesion (CAL) in acute stage Kawasaki disease (KD).MethodsBetween January 2018 and January 2021, a total of 102 children with acute stage KD were included in this retrospective study. Among them, 36 KD children with CAL were divided into the CAL group, and 66 KD children without CAL were divided into the NCAL group. Independent predictors of CAL in acute stage KD were identified by using univariate and multivariate logistic regression analysis. Spearman correlations were used to evaluate the association between CAL in acute stage KD and different indicators. The diagnostic performance of different indicators for CAL in acute stage KD was analyzed by the receiver operating characteristic (ROC) curve.ResultsCompared with the NCAL group, children in the CAL group had significantly higher white blood cell count, lymphocyte count, platelet count, D-dimer, and RDW levels, but lower PT levels (all p

ObjectiveTo study the practice of pharmaceutical services in internet-based psychiatric hospitals, and to analyze the prescriptions to ensure the safety and efficacy of internet-based medication in Wuxi, China.MethodsAll 1,259 internet-based prescriptions from our hospital in 2022 were collected, and data on patients’ age, gender, diagnosis, medications used, medication types, dosage forms, rationality of medication use, and reasons for irrationality were analyzed through descriptive statistics.ResultsIn the electronic prescriptions of internet-based psychiatric hospitals, females accounted for the majority (64.50%), with a female-to-male ratio of 1.82:1. Middle-aged and young adults accounted for the majority of patients (57.50%). There were 47 diagnosed diseases involved, with 89 types of medications used and 1,938prescriptions issued. Among them, there were 78 types of western medicine with 1,876 prescriptions (96.80%), and 11 types of traditional Chinese medicine with 62 prescriptions (3.20%). The main medications used were anti-anxiety and antidepressant medications (44.94%) and psychiatric medications (42.21%). The dosage forms were all oral, with tablets (78.53%), capsules (17.54%), and solution preparations (2.17%) being the top three in frequency. According to the prescription review results, the initial pass rate of internet-based system review was 64.26%. After intervention by the internet-based system and manual review by pharmacist reviewers, the final pass rate of internet-based prescriptions reached 99.76%.ConclusionThe practice of pharmaceutical services and prescription analysis in internet-based psychiatric hospitals could significantly improve medication rationality, which fills the research gap in this field. In addition, it promotes the transformation of pharmaceutical service models.

BackgroundIdentifying individuals at high risk of atherosclerotic cardiovascular disease (ASCVD) and implementing targeted prevention strategies might be the key to reducing the heavy disease burden in China. This study aimed to evaluate the prevalence, awareness, treatment, and risk factor control among individuals with high 10-year ASCVD risk in Guangzhou, China.MethodsThis study included 15,165 adults (aged 18 years and older) from 138 urban and rural communities in the 2018 survey of China Chronic Disease and Risk Factors Surveillance in Guangzhou. 10-year ASCVD risk was estimated using the risk assessment models recommended in the Chinese Guideline for the Prevention of Cardiovascular Disease 2017. The prevalence, awareness, treatment, and risk factor control of high ASCVD risk (defined as 10-year risk ≥10%) were examined.ResultsAmong the study population, the weighted proportion of men was 51.9%, and the mean age was 41.27 ± 0.52 years. The overall standardized prevalence of high 10-year ASCVD risk was 13.8% (95% CI, 12.4%–15.3%). The awareness rates for hypertension, diabetes, and hyperlipidemia were 48.0% (95% CI, 42.8%–53.4%), 48.3% (95% CI, 43.0%–53.7%), and 17.9% (95% CI, 14.4%–22.1%) among those with corresponding risk factors. The proportions of drug use in prevention were relatively low in primary prevention, with the rates of using BP-lowering, glucose-lowering, lipid-lowering, and aspirin being 37.7% (95% CI, 32.8%–42.8%), 41.4% (95% CI, 35.8%–47.3%), 6.7% (95% CI, 4.5%–10.0%), and 1.0% (95% CI, 0.6%–1.8%), respectively. As for risk factor control, only 29.3% (95% CI, 25.7%–33.2%), 16.8% (95% CI, 15.0%–18.6%), and 36.0% (95% CI, 31.1%–41.2%) of individuals with high ASCVD risk had ideal levels of blood pressure, LDL-C, and body weight.ConclusionThe estimated prevalence of 10-year high ASCVD risk was high in Guangzhou, while the rates of treatment and risk factor control in primary prevention were still far from optimal, especially for lipid management. These findings suggested that substantial improvement in ASCVD prevention is needed in this population.

ABSTRACT Clay soil results in higher crop yield and quality than sandy soil. However, irrigation causes clay soil to slump easily, increasing compactness and decreasing soil oxygen content. This study investigated the effects of dry seeding and wet emergence on the soil microenvironment and cotton growth promotion in Xinjiang silt loam fields. The experimental design included three aerated and three non-aerated treatments. The results showed that aerated irrigation decreased dry density of the 0–20 cm soil layer to different degrees, the field capacity increased to different degrees, and the dry density and field capacity of the 20-30 cm soil layer did not change among the different treatments. The dry density and field capacity of WP2 treatment changed the most, the dry density of 0-10 cm and 10-20 cm soil layer were respectively 1.28 g cm-3 and 1.27 g cm-3, and the field capacity were respectively 35.23% and 35.7%. Under the same irrigation quota, the soil water content of the aerated treatments was lower than that of the non-aerated treatments. Aerated irrigation inhibited the horizontal diffusion of water and facilitated downward water transport. The WP2 treatment had the highest peak soil temperature at depths of 10 and 20 cm, and the WP2 treatment had the highest numbers of bacteria, fungi, actinomycetes, urease, and catalase activities, seedling emergence, primary root length, plant height, and stem thickness.

Background: The Gitelman syndrome (GS) is an autosomal recessive disorder of renal tubular salt handling. Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation, and is caused by variants in the SLC12A3 gene. Gitelman syndrome has a heterogeneous phenotype, which may or may not include a range of clinical signs, posing certain difficulties for clinical diagnosis.Case presentation: A 49-year-old man was admitted to our hospital due to muscular weakness. The patient’s history revealed previous recurrent muscular weakness events associated with hypokalemia, featured by a minimum serum potassium value of 2.3 mmol/L. The reported male patient had persistent hypokalemia, hypocalciuria and normal blood pressure, without presenting obvious metabolic alkalosis, growth retardation, hypomagnesemia, hypochloremia or RAAS activation. We performed whole-exome sequencing and identified a novel compound heterozygous variant in the SLC12A3 gene, c.965-1_976delGCGGACATTTTTGinsACCGAAAATTTT in exon8 and c.1112T>C in exon9 in the proband.Conclusion: This is a study to report a heterogeneous phenotype Gitelman syndrome with a novel pathogenic compound heterozygous variant in the SLC12A3 gene. This genetic study expands the variants spectrum, and improve the diagnostic accuracy of Gitelman syndrome. Meanwhile, further functional studies are required to investigate the pathophysiological mechanisms of Gitelman syndrome.

Water pollution caused by widely used agricultural pesticide chlorpyrifos (CPF) has aroused extensive public concern. While previous studies have reported on toxic effect of CPF on aquatic animal, little is known about its effect on common carp (Cyprinus carpio L.) livers. In this experiment, we exposed common carp to CPF (11.6 μg/L) for 15, 30, and 45 days to establish a poisoning model. Histological observation, biochemical assay, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and integrated biomarker response (IBR) were applied to assess the hepatotoxicity of CPF in common carp. Our results displayed that CPF exposure damaged histostructural integrity and induced liver injury in common carp. Furthermore, we found that CPF-induced liver injury may be associated with mitochondrial dysfunction and autophagy, as evidenced by swollen mitochondria, broken mitochondrial ridges, and increased the number of autophagosomes. Moreover, CPF exposure decreased the activities of ATPase (Na+/K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, and Ca2+Mg2+-ATPase), altered glucose metabolism-related genes (GCK, PCK2, PHKB, GYS2, PGM1, and DLAT), and activated energy-sensing AMPK, indicating that CPF caused energy metabolism disorder. The activation of AMPK further induced mitophagy via AMPK/Drp1 pathway, and induced autophagy via AMPK/mTOR pathway. Additionally, we found that CPF induced oxidative stress (abnormal levels of SOD, GSH, MDA, and H2O2) in common carp livers, which further contributed to the induction of mitophagy and autophagy. Subsequently, we confirmed a time-dependent hepatotoxicity caused by CPF in common carp via IBR assessment. Our findings presented a new insight into molecular mechanism of CPF induced-hepatotoxicity in common carp, and provided a theoretical basis for evaluating CPF toxicity to aquatic organisms.

Electronic cigarette (e-cigarette) use is becoming more widespread, and studies show that they are not absolutely harmless. To investigate the association between the dual use of e-cigarettes and marijuana with sleep duration among adults in the United States, this cross-sectional study used data from 6,573 participants aged 18–64 years from 2015 to 2018 from the National Health and Nutrition Examination Survey database. Chi-square tests and analysis of variance were used for bivariate analyses of binary and continuous variables, respectively. Multinomial logistic regression models were used for univariate and multivariate analyses of e-cigarette use, marijuana use, and sleep duration. Sensitivity analyses were conducted in populations with dual e-cigarette and traditional cigarette use and dual marijuana and traditional cigarette use. People who concurrently use e-cigarettes and marijuana had higher odds of not having the recommended sleep duration than neither users (short sleep duration: odds ratio [OR], 2.34; 95% confidence interval [CI], 1.19–4.61; P = 0.014; long sleep duration: OR, 2.09; 95% CI, 1.53–2.87; P

This study aimed to investigate the effects of tea polyphenol (TP), epigallocatechin gallate (EGCG), and their palmitic acid-modified derivatives palmitoyl-TP (pTP) and palmitoyl-EGCG (pEGCG) on the accumulation of N-nitrosamine and biogenic amines (BAs), residual nitrites, and lipid oxidation in Chinese sausages. The microorganisms, color, and texture properties of sausages were evaluated. TP, EGCG, pTP, or pEGCG significantly inhibited the accumulation of N-nitrosodimethylamine (NDMA) and BAs, residual nitrites, and lipid oxidation, but enhanced the redness, hardness, and chewiness of sausages. The concentration of NDMA in sausages was reduced by 58.11%, 63.51%, 36.49%, and 44.59%, respectively, after treatment with TP, EGCG, pTP, and pEGCG. Both EGCG and pEGCG exhibited excellent inhibitory effects on the predominant BAs, including putrescine, tyramine, cadaverine, histamine, and 2-phenylethylamine. Palmitoyl-EGCG was found to be the strongest inhibitor of lipid oxidation. Besides, the four antioxidants weakly affected the population of total aerobic bacteria and lactic acid bacteria but totally suppressed the growth of undesirable Enterobacteriaceae. The principal component and correlation analyses proved that BAs, nitrites, lipid oxidation, and microbiota were responsible for the formation of NDMA. The results indicated that palmitic acid-modified TPs and similar derivatives might serve as potential preservatives to improve the safety and quality of fermented meat products.

Low-temperature stress during stem elongation is a major factor limiting wheat yield. While calcium (Ca2+) is known to enhance stress tolerance, it’s potential as an alternative to cold priming and the underlying mechanisms in wheat remains unclear. The current study assessed the effects of exogenous Ca2+ and calcium inhibitors on wheat growth and related physiology mechanisms under low-temperature stress. The results revealed that exogenous Ca2+ increased photosynthesis and antioxidant capacity, lowered cell membrane damage, and ultimately enhanced tolerance to low-temperature stress during the stem elongation stage, compared with the non-exogenous Ca2+ treatment. Moreover, exogenous Ca2+ induced endogenous Ca2+ content and triggered the upregulation of Ca2+ signaling and cold-responsive related genes. This study highlights the significance of exogenous Ca2+ in enhancing stress tolerance and contributing to wheat yield improvement under low-temperature stress.

Grain filling is essential for wheat yield formation, but is very susceptible to environmental stresses, such as high temperatures, especially in the context of global climate change. Grain RGB images include rich color, shape, and texture information, which can explicitly reveal the dynamics of grain filling. However, it is still challenging to further quantitatively predict the days after anthesis (DAA) from grain RGB images to monitor grain development. Results: The WheatGrain dataset revealed dynamic changes in color, shape, and texture traits during grain development. To predict the DAA from RGB images of wheat grains, we tested the performance of traditional machine learning, deep learning, and few-shot learning on this dataset. The results showed that Random Forest (RF) had the best accuracy of the traditional machine learning algorithms, but it was far less accurate than all deep learning algorithms. The precision and recall of the deep learning classification model using Vision Transformer (ViT) were the highest, 99.03% and 99.00%, respectively. In addition, few-shot learning could realize fine-grained image recognition for wheat grains, and it had a higher accuracy and recall rate in the case of 5-shot, which were 96.86% and 96.67%, respectively. Materials and Methods: In this work, we proposed a complete wheat grain dataset, WheatGrain, which covers thousands of wheat grain images from 6 DAA to 39 DAA, which can characterize the complete dynamics of grain development. At the same time, we built different algorithms to predict the DAA, including traditional machine learning, deep learning, and few-shot learning, in this dataset, and evaluated the performance of all models. Conclusions: To obtain wheat grain filling dynamics promptly, this study proposed an RGB dataset for the whole growth period of grain development. In addition, detailed comparisons were conducted between traditional machine learning, deep learning, and few-shot learning, which provided the possibility of recognizing the DAA of the grain timely. These results revealed that the ViT could improve the performance of deep learning in predicting the DAA, while few-shot learning could reduce the need for a number of datasets. This work provides a new approach to monitoring wheat grain filling dynamics, and it is beneficial for disaster prevention and improvement of wheat production.

Over the past few years, China has become a hotspot for the domestication of the commercially valuable largemouth bass (Micropterus salmoides). Although the food preference of this fish has been studied, little is known about the genes regulating its growth. Population breeding was performed using two indigenous strains (QT1 and QT2), with the results showing that the organ/body ratio, abdominal fat rate and the body weight gain of QT1 and QT2 were higher than for the offspring YL1 and Y3 which are extensively cultured in China. Subsequent RNA sequencing (RNA-Seq) allowed for the identification of potential genes and pathways involved in growth performance. Overall, the transcriptome analysis generated 89,056 transcripts and 42,529 Unigenes. A PCA revealed significant differences between QT1 and the other three strains, while the other three strains did not show much difference. A KEGG enrichment analysis of differentially expressed genes showed that steroid biosynthesis was the most enriched pathway among the four strains. These pathways could be related to the growth of largemouth bass. In addition, a co-expression network analysis suggested a strong interaction between liver steroid biosynthesis and the genes for photosynthesis, secondary metabolism and stress response. Taken together, the above results can provide new insights into the liver metabolism of different strains of largemouth bass during culture and provide references for the subsequent domestication and breeding programs of largemouth bass.

Abstract Background This study aims to investigate the potential association of peripheral inflammatory blood cell parameters with the incidence and progression of chronic kidney disease (CKD) in patients with diabetes. Methods The cross‐sectional study included 1192 subjects with diabetes derived from one center. The cohort study included 2060 subjects with diabetes derived from another two centers followed up for 4 years. Logistic regression and Cox proportional hazards models were used to evaluate the association of peripheral inflammatory blood cell with CKD. Results In the cross‐sectional study, neutrophil count performed best as an independent risk factor for CKD (odds ratio 2.556 [95% confidence interval 1.111, 5.879]) even after 1:1 case–control matching for age, gender, history of high blood pressure and duration of diabetes. Spline regression revealed a significant linear association of CKD incidence with continuous neutrophil count in excess of 3.6 × 109/L. In the cohort study, subjects were grouped based on tertile of neutrophil count and neutrophil‐to‐lymphocyte ratio. Cox regression analysis results showed that only neutrophil count was independently associated with CKD progression (the highest group vs. the lowest group, hazard ratio 2.293 [95% confidence interval 1.260, 4.171]) after fully adjusting for potential confounders. The cumulative incidence of CKD progression in patients with diabetes gradually increased with increasing neutrophil count (53 (7.7%) subjects in the lowest group vs. 60 (8.2%) in the middle group vs. 78 (12.2%) in the highest group). Conclusions This study suggested that neutrophil count is an independent risk factor for progression of CKD in patients with diabetes.

Abstract Background Estrogen has been usually used in clinic for medical pretreatment of early pregnancy loss. There was little reported the effect of estrogen combined with prostaglandin analogs in the medical management of early pregnancy loss. This retrospective study aimed to evaluate the efficacy of estrogen pretreatment for medical management of early pregnancy loss and explore the confounding factor of intrauterine adhesion (IUA) on the outcome of medical management. Methods A total of 226 early pregnancy loss patients who received pretreatment with estradiol valerate and/or mifepristone, followed by carboprost methylate suppositories (study groups), or carboprost methylate suppositories alone (control group) in a regional central institution from March 2020 to February 2021 were retrospectively studied. All patients were evaluated by hysteroscopy 6 h after carboprost methylate suppositories use to assess whether the gestational sac was complete expulsion and assess the morphology of uterine cavity. Results The complete expulsion rate was 56.94% in the mifepristone and estradiol valerate-pretreatment group, 20.69% in the estradiol valerate-pretreatment group, 62.5% in the mifepristone-pretreatment group, and 12.5% in the control group. Compared with the control group, pretreatment with estradiol valerate did not increase the complete expulsion rate significantly (P = 0.297), pretreatment with mifepristone increased the complete expulsion rate significantly (P

Abstract Objective This study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women. Methods NIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV. Results Among the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups. Conclusion NIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.

Abstract p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53–MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53–MDM2 interaction.

Laboratory analysis of returned Chang’E-5 samples from the lunar surface show their hydroxyl contents to be on the weak end of lunar hydration features.