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Magnetic Resonance Imaging (MRI) is a globally acknowledged diagnostic procedure particularly recognized for its superior soft tissue contrast, high-resolution imaging, and non-ionizing radiation properties, making it an indispensable tool in the medical field. However, to optimize MRI’s sensitivity and specificity towards certain diseases, use of contrast agents becomes necessary. Recent developments focus on nanomaterial-based MRI contrast agents to improve diagnostic accuracy and image quality. This review highlights advancements in such agents, including metal oxide nanoparticles, carbon-based materials, gold nanoparticles, and quantum dots. It discusses their roles in MRI-guided therapies like targeted drug delivery, hyperthermia, radiation therapy, photodynamic therapy, immunity-boosting therapy, and gene therapy. Insights into the future potential of MRI contrast agents in imaging medicine are also provided.

The Yan’an gas field in the Ordos Basin is a typical deep coalbed methane field with tremendous resource potential. Evaluation methods for gas content in deep coal seams are urgently required to be established. This study is aimed at quantitatively analyzing the gas content of coalbed methane in deep coalbed methane reservoirs and revealing its influencing factors. With the coal rock samples of typical deep coalbed methane wells in the Yan’an gas field of the Ordos Basin as the research objects, the gas-bearing characteristics of deep coal rocks were analyzed, and the main controlling factors of gas-bearing properties were explored. The research results indicate that (1) the deep coal seams in the Yan’an gas field have a considerable thickness, a high total organic carbon content, and the potential of pyrolysis hydrocarbon generation is generally elevated, presenting excellent hydrocarbon generation potential. (2) Various types of pores and fractures in the deep coal rocks of the Yan’an gas field are well-developed, providing a favorable preservation space and migration channel for deep coalbed methane. (3) The total gas content of on-site analysis of deep coalbed methane in the Yan’an gas field is relatively high, mainly existing in the form of free gas, and has significant exploration and development potential. (4) The gas content of deep coal rocks in the Yan’an gas field is jointly controlled by multiple factors such as the total organic carbon content, minerals, and pore structure. In conclusion, the deep coal seams in the Yan’an gas field have favorable reservoir-forming conditions and great exploration and development potential.

Lilium brownii var. viridulum, known as Longya lily, is a well-known medicinal and edible plant in China. Bulb rot is a common disease in Longya lily cultivation that severely affects the yield and quality of lilies. According field investigations, we found that different Longya lily plants in the same field had different degrees of resistance to root rot. To find the reasons leading to the difference, we performed metabolomic and transcriptomic analyses of Longya lily with different degrees of disease. The transcriptomic analyses showed that the number of differentially expressed genes increased in early and mid-stage infections (LYBH2 and LYBH3), while decreased in late-stage infection (LYBH4). A total of 2309 DEGs showed the same expression trend in diseased bulb compared healthy bulb (LYBH1). The transcription factors (TFs) analysis of DEGs showed that several common TFs, like WRKY, bHLH, AP2/ERF-ERF and MYB, were significantly activated in bulbs after decay. The metabolomic analyses showed that there were 794 differentially accumulated metabolites, and metabolites with significant changes in relative content largely were phenolic acids, followed by flavonoids and amino acids and derivatives. The combined analysis of transcriptome and metabolome indicated that phenylpropanoid biosynthesis pathway was crucial in Longya lily resistance to bulb rot. Therefore, we speculated that the different degree of resistance to bulb rot in Longya lily may be related to the transcript levels of gene and contents of metabolites in the phenylpropanoid biosynthesis pathway. Overall, these results elucidate the molecular responses of Longya lily to bulb rot and lay a theoretical foundation for breeding resistant varieties.

The myosin heavy chain 9 (MYH9) gene, located on human chromosome 22, encodes non-muscle myosin heavy chain IIA (NM IIA). This protein is essential to various cellular events, such as generating intracellular chemomechanical force and facilitating the movement of the actin cytoskeleton. Mutations associated with thrombocytopenia in autosomal dominant diseases first highlighted the significance of the MYH9 gene. In recent years, numerous studies have demonstrated the pivotal roles of MYH9 in various cancers. However, its effects on cancer are intricate and not fully comprehended. Furthermore, the elevated expression of MYH9 in certain malignancies suggests its potential as a target for tumor therapy. Nonetheless, there is a paucity of literature summarizing MYH9’s role in tumors and the therapeutic strategies centered on it, necessitating a systematic analysis. This paper comprehensively reviews and analyzes the pertinent literature in this domain, elucidating the fundamental structural characteristics, biological functions, and the nexus between MYH9 and tumors. The mechanisms through which MYH9 contributes to tumor development and its multifaceted roles in the tumorigenic process are also explored. Additionally, we discuss the relationship between MYH9-related diseases (MYH9-RD) and tumors and also summarize tumor therapeutic approaches targeting MYH9. The potential clinical applications of studying the MYH9 gene include improving early diagnosis, clinical staging, and prognosis of tumors. This paper is anticipated to provide novel insights for tumor therapy.

BackgroundThe widespread use of smartphones has significantly increased smartphone addiction among college students, especially during the COVID-19 pandemic. Since the COVID-19 outbreak, university campuses in mainland China have strictly followed the Chinese government’s strict quarantine policy, including closed campus management, prohibitions against gatherings, and social distancing, increasing student loneliness and anxiety and thus increasing the risk of smartphone addiction. Extant Studies have revealed that social isolation is a prominent predictor of smartphone addiction but have failed to systematically explore the complex relationship between social isolation and smartphone addiction in the context of COVID-19; therefore, the underlying mechanisms of these factors in the post-pandemic era are unclear.ObjectiveThis study is the first attempt to consider loneliness, COVID-19 anxiety and social isolation as a whole and to clarify the underlying mechanisms of social isolation and smartphone addiction by constructing a multiple mediating model.MethodThis study included students enrolled at eight higher education institutions in Conghua District (Guangzhou city). Quota proportional sampling was adopted, 900 self-report questionnaires were distributed through the WeChat groups of these universities from December 10 to December 15, 2022, and 868 valid questionnaires (620 females, 248 males) were ultimately obtained.ResultsThe direct effect of social isolation on smartphone addiction was significant, and loneliness and COVID-19 anxiety mediated the association between social isolation and smartphone addiction in both parallel and sequential ways. Moreover, a reverse mediation model with COVID-19 anxiety as the first mediator and loneliness as the second mediator was found.ConclusionCollege students who experience social isolation are at greater risk for smartphone addiction, and the core factor leading to their smartphone addiction is the subjective psychological state triggered by campus isolation and social distancing, such as loneliness and anxiety. These risky behaviors of people should receive extra attention, and psychological factors such as loneliness and COVID-19 anxiety should be considered in future therapies aimed at reducing addiction.

Introduction: The carbon storage service of ecosystems in ecologically fragile areas is highly sensitive to regional land use/land cover (LULC) changes. Predicting changes in regional carbon storage under different LULC scenarios is crucial for land use management decisions and exploring carbon sink potential. This study focuses on the Luan River Basin, a typical ecologically fragile area, to analyze the impact of LULC changes on carbon storage.Methods: The PLUS-InVEST model was employed to simulate LULC patterns for the year 2030 under three scenarios: natural development, cropland protection and urban development, and ecological protection. The model projected the future carbon sink potential of the basin under these scenarios.Results: From 2000 to 2020, carbon storage showed a trend of decrease followed by an increase. By 2030, compared to 2020, carbon storage is projected to increase by 16.97% under the ecological protection scenario and decrease by 22.14% under the cropland protection and urban development scenario. The increase in carbon storage was primarily due to the conversion of cropland and grassland to forestland, while the decrease was mainly associated with the conversion of forestland to grassland and cropland, and the transformation of grassland to cropland and construction land. In the potential LULC scenarios of 2030, certain regions within the basin exhibited unstable carbon sink potential, strongly influenced by LULC changes. These areas were predominantly characterized by artificially cultivated forests, shrubs, and agricultural land. Implementing appropriate forest management measures and optimizing agricultural land management practices are essential to enhance carbon sink potential in these regions. Population density, annual average temperature, and DEM (Digital Elevation Model) were the dominant factors driving the spatial variation of carbon sink potential in the Luan River Basin.Discussion: The research results provide a theoretical basis for rational planning of land use and the enhancement of carbon sink potential in ecologically fragile regions.

IntroductionIn infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles.MethodsUsing 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators.ResultsPrincipal component analysis using Bray–Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA.ConclusionThe varying “enterohepatic circulation” status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

PurposeBrain metastasis (BM) from non-small cell lung cancer (NSCLC) is a serious complication severely affecting patients’ prognoses. We aimed to compare the clinicopathological features and prognosis of synchronous and metachronous BM from NSCLC.MethodsClinical data of 461 patients with brain metastases from NSCLC who visited the Cancer Hospital of China Medical University from 2005 to 2017 were retrospectively collected. We analyzed the pathophysiological characteristics of synchronous and metachronous BM from NSCLC and survival rates of the patients. Propensity score matching analysis was used to reduce bias between groups. In addition, we used the Kaplan-Meier method for survival analysis, log-rank test to compare survival rates, and Cox proportional hazards regression model for multivariate prognosis analysis.ResultsAmong 461 patients with BM, the number of people who met the inclusion criteria was 400 cases, and after 1:2 propensity score matching,130 had synchronous BM and 260 had metachronous BM. The survival time was longer for metachronous BM in driver mutation-negative patients with squamous cell carcinoma than synchronous BM. Conversely, metachronous and synchronous BM with gene mutations and adenocarcinoma showed no differences in survival time. Multivariate analysis showed that metachronous BM was an independent prognostic factor for overall survival. Furthermore, the pathological type squamous cell carcinoma and Karnofsky Performance Status score

With the outbreak of the COVID pandemic, preservice teachers have experienced an unprecedented situation and faced various kinds of issues due to uncertain learning and teaching environments. As a result, they felt insecure and disappointed about their teaching performance during student teaching. Self-efficacy to teach and pedagogical beliefs are crucial elements that influence preservice teachers’ teaching performance during student teaching and their professional development in the early stage. This study adopted a quantitative research method to examine the changes in the self-efficacy and pedagogical beliefs of preservice teachers after student teaching during the initial teacher education stage in the Japanese context and how preservice teachers’ self-efficacy and pedagogical beliefs changed during the COVID-19 pandemic. A sample of 133 preservice primary teachers in a university in Western Japan was recruited in this study. Two structured surveys were used to collect the data, and factor analyses and paired t-tests were fitted. This study verified the validity and internal consistency of two surveys in the Japanese context. The results showed that the Japanese preservice teachers’ self-efficacy made a steeper change after student teaching. Their pedagogical beliefs increased significantly, however, yielded a small effect. The results suggested that student teaching is an essential source of influence on preservice teachers’ self-efficacy and pedagogical beliefs. This study contributes to the meaningful application of theories developed in the West to Japan by highlighting the Japanese educational context. This study provides implications for effectively reinforcing preservice teachers’ self-efficacy and pedagogical beliefs through developing deeper reflection skills, thus supporting them to overcome various challenges in their future teaching careers.

BackgroundWe aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy, as well as changes in serum levels of inflammatory factors (TNF-α, IL-6, and IL-10) in the perioperative period.MethodsSixty patients who underwent laparoscopic gallbladder-preserving cholecystolithotomy were evenly divided into oxycodone (O) and sufentanil (S) groups. In groups O and S, oxycodone (0.3 mg/kg) and sufentanil (0.3 ug/kg) were administered, respectively, followed by propofol (2 mg/kg) and rocuronium (0.6 mg/kg). In both groups, the intraoperative electroencephalography double-frequency index was used to guide the use of sedative and analgesic drugs, assessing the follow-up analgesic effect (VAS), degree of sedation (Ramsey), and postoperative complications at seven different time points (0, 0.5, 2, 4, 6, 8, and 24 h postoperatively).ResultsCompared with the S group, patients in the O group exhibited lower VAS scores within 24 h postoperatively (P 0.05). Regarding postoperative awakening and extubation duration, O group patients experienced shorter times and better remedial analgesia (P

ObjectiveMajor pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC.MethodsThis retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups.ResultsIn total, 91 LUSC patients who met the study’s eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001).ConclusionThe MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

High electric fields affect the diffusion dynamics of atoms on a metal surface, causing biased surface diffusion that possibly leads to the growth of intensively field emitting protrusions and consequent vacuum breakdown (VBD). The scientific understanding of this process, as well as other fundamental VBD initiation mechanisms, is far from complete. Here we investigate the exact atomic behaviour of metal surfaces exposed to extremely high electric fields using density functional theory (DFT). Previous theories describe the field-surface dynamics in terms of the effective dipole moments and polarizability of surface atoms, disregarding higher-order (hyperpolarizability) terms. The validity of this approximation has been evaluated only for electric fields up to 3 GV/m, due to computational limitations of the plane-wave DFT basis used in previous works. In this work, we test the validity of this approximation for a much wider field range, relevant for VBD and field emission (FE), using Cu nanoparticles as our test structures. We find that although such high fields can change the entire structure of Cu nanoparticles, their energetics are described very precisely by the permanent dipole moment and polarizability terms. Thus, we show that neglecting the hyperpolarizability terms is valid even for field values that exceeds the range that is relevant for intense FE and VBD. This work lays a solid foundation for further developing atomic-level simulation models for electric field-induced surface diffusion on metal surfaces and its effects on protrusion growth and VBD initiation.

PurposeThis study aimed to investigate the effect of Marshall ethanol infusion (VOM-Et) in the vein on mitral isthmus (MI) ablation.MethodsPatients with persistent atrial fibrillation (AF) were grouped into vein of VOM-Et combined with radiofrequency (RF) ablation (VOM-Et-RF) and RF groups. The primary outcome was MI block immediate block rate after surgery. Stratified analysis was also performed for factors affecting the outcome measures.ResultsA total of 118 consecutive patients underwent AF ablation at Taizhou Hospital of Zhejiang Province from January 2018 to December 2021. Successful bidirectional perimitral block was achieved in 96% of patients in VOM-Et-RF (69 of 72) and in 76% of patients in the RF group (35 of 46) (P

Maire yew (Taxus mairei), an evergreen conifer, has high ornamental and medicinal value. The arils of this species has three different colors. However, the variation mechanisms of arils color formation remains unclear. Here, the gene expression and metabolite concentration were profiled for red (RTM), yellow (YTM), and purple (PTM) arils in different developmental stages. A total of 266 flavonoids and 35 carotenoids were identified. The predominant pigments identified in YTM were epiafzelechin, lutein, and β-Cryptoxanthin, while malvidin-3,5-di-O-glucoside and apigenin played crucial roles in PTM. And significant differential expression was observed among the HCT, DFR, LAR, ANS, crtB, NCED, and CCoAOMT genes across different color arils. During the maturation of yellow arils, the upregulation of HCT was strongly correlated with the accumulation of epiafzelechin. The diminished expression of DFR, LAR, and ANS seemed to inhibit the production of delphinidin-3-O-rutinoside. The decrease in crtB expression and concurrent increase in NCED expression potentially regulate the heightened accumulation of lutein. Meanwhile, the accumulation of β-cryptoxanthin appeared seemed to be positively influenced by NCED. As aril turning purple, the decreased expression of CCoAOMT seemed to facilitate the synthesis of apigenin. The substantial upregulation of DFR promoted the production of malvidin-3,5-di-O-glucoside. Additionally, the overexpression of MYBs may plays the important role in regulating the formation of different colored arils. In total, 14 genes were selected for qRT-PCR validation, the results indicated the reliability of the transcriptome sequences data. Our findings could provide valuable insight into the molecular breeding, development, and application of Maire yew resources.

As a unique and native conifer in China, Platycladus orientalis is widely used in soil erosion control, garden landscapes, timber, and traditional Chinese medicine. However, due to the lack of reference genome and transcriptome, it is limited to the further molecular mechanism research and gene function mining. To develop a full-length reference transcriptome, tissues from five different parts of P. orientalis and four cone developmental stages were sequenced and analyzed by single-molecule real-time (SMRT) sequencing through the PacBio platform in this study. Overall, 37,111 isoforms were detected by PacBio with an N50 length of 2,317 nt, an average length of 1,999 bp, and the GC content of 41.81%. Meanwhile, 36,120 coding sequences, 5,645 simple sequence repeats (SSRs), 1,201 non-coding RNAs (lncRNAs), and 182 alternative splicing (AS) events with five types were identified using the results obtained from the PacBio transcript isoforms. Furthermore, 1,659 transcription factors (TFs) were detected and belonged to 51 TF families. A total of 35,689 transcripts (96.17%) were annotated through the NCBI nr, KOG, Swiss-Prot and KEGG databases, and 385 transcript isoforms related to 8 types of hormones were identified incorporated into plant hormone signal transduction pathways. The assembly and revelation of the full-length transcriptome of P. orientalis offer a pioneering insight for future investigations into gene function and genetic breeding within Platycladus species.

Microorganisms are important sources of lipolytic enzymes with characteristics for wide promising usages in the specific industrial biotechnology. The cellulolytic myxobacterium Sorangium cellulosum is rich of lipolytic enzymes in the genome, but little has been investigated. Here, we discerned 406 potential lipolytic enzymes in 13 sequenced S. cellulosum genomes. These lipolytic enzymes belonged to 12 families, and most are novel with low identities (14–37%) to those reported. We characterized a new carboxylesterase, LipB, from the alkaline-adaptive So0157-2. This enzyme, belonging to family VIII, hydrolyzed glyceryl tributyrate and p-nitrophenyl esters with short chain fatty acids (≤C12), and exhibited the highest activity against p-nitrophenyl butyrate. It retained over 50% of the activities in a broad temperature range (from 20°C to 60°C), alkaline conditions (pH 8.0–9.5), and the enzymatic activity was stable with methanol, ethanol and isopropanol, and stimulated significantly in the presence of 5 mM Ni2+. LipB also exhibited β-lactamase activity on nitrocefin, but not ampicillin, cefotaxime and imipenem. The bioinformatic analysis and specific enzymatic characteristics indicate that S. cellulosum is a promising resource to explore lipolytic enzymes for industrial adaptations.

Climate change adaptation is increasingly recognized by subsistence farmers in Pakistan. The problem of climate change is severe, and smallholders are often resource constrained when it comes to adapting to it. However, such constraints can be overcome through collective responses. Therefore, it is necessary to evaluate the impact of collective action among smallholder farmers to determine how it influences local adaptation processes. This study explores the impact of farmer’s collective action groups (CAGs) on adopting climate-smart agricultural (CSA) practices in poverty-stricken areas of rural Punjab, Pakistan. The data was collected through a cross-sectional survey, and for the analysis purpose, the Recursive bivariate probit regression (RBP) model was employed. The first stage estimates of RBP models suggest that the farmer’s decision to participate in CAGs is mainly influenced by factors such as education, credit access, climate change risk perception, and peer influence. The second stage estimates showed a positive and significant impact of farmers’ participation in collective action groups on adopting climate change adaptation strategies across all three models. The study concludes that the farmers participating in collective action groups have a higher climate change adaptation level. It is recommended that the pro-poor policies be designed to negate the entry barriers, facilitate the inclusion of the farmers in the collective action groups, and enhance climate change adaptation among smallholders.

Purpose: Dexmedetomidine exerts a sedative effect by promoting the sleep pathway endogenously and producing a state similar to N2 sleep. This study aimed to study the efficacy and safety of dexmedetomidine nasal spray in the treatment of postoperative sleep disturbance.Methods: This study enrolled 120 participants [men and women; age, 18–40 years; American Society of Anesthesiologists grade, I or II] who underwent maxillofacial surgery under general anesthesia through nasotracheal intubation. The participants were randomly divided into three groups: blank control group (BC group), 1.0 μg/kg dexmedetomidine group (1.0 Dex group), and 1.5 μg/kg dexmedetomidine group (1.5 Dex group), with 40 patients allocated to each group. At 21:30 on the night after the operation, the intervention groups were administered their corresponding doses of dexmedetomidine nasal spray. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate the baseline sleep status of participants 1 month preoperatively and on the night after the operation. Polysomnography (PSG) was used to record the sleep status on the night after the operation. We recorded the rescue times of sedative and analgesic drugs on the first night after surgery, adverse reactions, total hospital stay duration, and total costs.Results: Compared with patients in the BC group, those in 1.0 Dex and 1.5 Dex groups had longer N2 sleep duration, were awake for a shorter time after dose administration, woke up less often, and had significantly improved sleep efficiency (p < 0.05). Compared with the BC group, the PSQI scores of 1.0 Dex and 1.5 Dex groups were significantly lower on the night after operation, and the proportion of PSQI > 5 was significantly lower (p < 0.05). Compared with patients in the BC group and the 1.0 Dex group, those in the 1.5 Dex group had significantly prolonged N3 sleep, reduced frequency of requiring sufentanil rescue, lower incidence of sore throat after surgery, and shorter average length of hospital stay (all, p < 0.05).Conclusion: The sleep quality of participants on the night after having undergone maxillofacial surgery was safely and effectively improved by 1.0–1.5 μg/kg dexmedetomidine atomized nasal sprays. Notably, only the latter could prolong N3 sleep. Level of Evidence II: Evidence was obtained from at least one properly designed randomized controlled trial.

The effectiveness of COVID-19 vaccines wanes over time and the emergence of the SARS-CoV-2 Omicron variant led to the accelerated expansion of efforts for booster vaccination. However, the effect and contribution of booster vaccination with inactivated COVID-19 vaccines remain to be evaluated. We conducted a retrospective close contacts cohort study to analyze the epidemiological characteristics and Omicron infection risk, and to evaluate the effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection, symptomatic COVID-19, and COVID-19 pneumonia during the outbreaks of Omicron BA.2 infection from 1 February to 31 July 2022 in Guangdong, China. A total of 46,547 close contacts were identified while 6.3% contracted Omicron BA.2 infection, 1.8% were asymptomatic infection, 4.1% developed mild COVID-19, and 0.3% had COVID-19 pneumonia. We found that females and individuals aged 0-17 or ≥ 60 years old were more prone to SARS-CoV-2 infection. The vaccinated individuals showed lower infection risk when compared with the unvaccinated people. The effectiveness of booster vaccination with inactivated COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 was 28.6% (95% CI: 11.6%, 35.0%) and 39.6% (95% CI: 30.0, 47.9) among adults aged ≥ 18 years old, respectively when compared with full vaccination. Booster vaccination provided a moderate level of protection against SARS-CoV-2 infection (VE: 49.9%, 95% CI: 22.3%-67.7%) and symptomatic COVID-19 (VE: 62.6%, 95% CI: 36.2%-78.0%) among adults aged ≥ 60 years old. Moreover, the effectiveness of booster vaccination was 52.2% (95% CI: 21.3%, 70.9%) and 83.8% (95% CI: 28.1%, 96.3%) against COVID-19 pneumonia in adults aged ≥ 18 and ≥ 60 years old, respectively. The reduction of absolute risk rate of COVID-19 pneumonia in the booster vaccination group was 0·96% (95% CI: 0.33%, 1.11%), and the number needed to vaccinate to prevent one case of COVID-19 pneumonia was 104 (95% CI: 91, 303) in adults aged ≥ 60 years old. In summary, booster vaccination with inactivated COVID-19 vaccines provides a low level of protection against infection and symptomatic in adults of 18-59 years old, and a moderate level of protection in older adults of more than 60 years old, but a high level of protection against COVID-19 pneumonia in older adults.

Building preservice teachers' capacities with in-depth reflections on their acquired knowledge and practicum practice has become indispensable in teacher education programs' current field experience requirements. Lengthy training programs with blended learning have successfully promoted reflection in preservice teachers. However, it is unclear whether preservice teachers could benefit from a short self-access online training program (SSOTP) in promoting their reflection depths, especially when facing challenging situations such as COVID-19. Using a teaching and assessing reflective learning model, we examined reflection depth among Chinese preservice teachers in a quasi-experimental research approach. This study showed the effectiveness of an SSOTP in stimulating preservice teachers' reflection depth. The training sequence and different topics also significantly affected preservice teachers in generating reflections. The results suggested that establishing an SSOTP with systematic stimulations could enhance preservice teachers' reflection depths and help them achieve quality teaching during the teacher preparation stage. While preservice teachers generated many reflective statements, their reflection depths were relatively shallow. This study provides evidence to enhance different levels of reflection depth in future SSOTPs.

BackgroundLower-grade glioma (LGG) is a primary intracranial tumor that carry a high risk of malignant transformation and limited therapeutic options. Emerging evidence indicates that the tumor microenvironment (TME) is a superior predictor for tumor progression and therapy response. PLEKHA4 has been demonstrated to be a biomarker for LGG that correlate with immune infiltration. However, the fundamental mechanism by which PLEKHA4 contributes to LGG is still poorly understood.MethodsMultiple bioinformatic tools, including Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA2), Shiny Methylation Analysis Resource Tool (SMART), etc., were incorporated to analyze the PLEKHA4. ESTIMATE, ssGSEA, CIBERSORT, TIDE and CellMiner algorithms were employed to determine the association of PLEKHA4 with TME, immunotherapy response and drug sensitivities. Immunohistochemistry (IHC)-based tissue microarrays and M2 macrophage infiltration assay were conducted to verify their associations.ResultsPLEKHA4 expression was found to be dramatically upregulated and strongly associated with unfavorable overall survival (OS) and disease-specific survival (DSS) in LGG patients, as well as their poor clinicopathological characteristics. Cox regression analysis identified that PLEKHA4 was an independent prognostic factor. Methylation analysis revealed that DNA methylation correlates with PLEKHA4 expression and indicates a better outcome in LGG. Moreover, PLEKHA4 was remarkably correlated with immune responses and TME remodeling, as evidenced by its positive correlation with particular immune marker subsets and the putative infiltration of immune cells. Surprisingly, the proportion of M2 macrophages in TME was strikingly higher than others, inferring that PLEKHA4 may regulate the infiltration and polarization of M2 macrophages. Evidence provided by IHC-based tissue microarrays and M2 macrophage infiltration assay further validated our findings. Moreover, PLEKHA4 expression was found to be significantly correlated with chemokines, interleukins, and their receptors, further supporting the critical role of PLEKHA4 in reshaping the TME. Additionally, we found that PLEKHA4 expression was closely associated with drug sensitivities and immunotherapy responses, indicating that PLEKHA4 expression also had potential clinical significance in guiding immunotherapy and chemotherapy in LGG.ConclusionPLEKHA4 plays a pivotal role in reshaping the TME of LGG patients, and may serve as a potential predictor for LGG prognosis and therapy.

BackgroundPrevious observational studies have shown that a potential relationship between anti-Helicobacter pylori (H. pylori) IgG levels and Myocardial Infarction (MI). Nevertheless, the evidence for the causal inferences remains disputable. To further clarify the relationship between anti-H. pylori IgG levels and MI and explore its pathogenesis, we conducted a Mendelian randomization (MR) analysis.MethodsIn this study, we used two-sample Mendelian Randomization (MR) to assess the causality of anti-H. pylori IgG levels on MI and potential pathogenesis, 12 single nucleotide polymorphisms (SNPs) related to anti-H. pylori IgG levels were obtained from the European Bioinformatics Institute (EBI). Summary data from a large-scale GWAS meta-analysis of MI was utilized as the outcome dataset. Summary data of mediators was obtained from the FinnGen database, the UK Biobank, the EBI database, MRC-IEU database, the International Consortium of Blood Pressure, the Consortium of Within family GWAS. Inverse variance weighted (IVW) analysis under the fixed effect model was identified as our main method. To ensure the reliability of the findings, many sensitivity analyses were performed.ResultsOur study revealed that increases of anti-H. pylori IgG levels were significantly related to an increased risk of MI (OR, 1.104; 95% CI,1.042–1.169; p = 7.084 × 10−4) and decreases in HDL cholesterol levels (β, −0.016; 95% CI, −0.026 to −0.006; p = 2.02 × 10−3). In addition, there was no heterogeneity or pleiotropy in our findings.ConclusionThis two-sample MR analysis revealed the causality of anti-H. pylori IgG levels on MI, which might be explained by lower HDL cholesterol levels. Further research is needed to clarify the results.

To grasp the phase change characteristics of the filling slurry from fluid to solid state in time, conducted a study on the setting characteristics of the filling slurry with different aggregate combinations, and analyzed the law of the initial and final setting time with the change of the amount of cementation powder, filling plant tailings, tailing pond tailings, and water. The results show that the initial and final setting time of the filling slurry prepared from the tailings of the filling plant is proportional to the concentration, and is positively correlated with the slope decline of the sand-cement ratio. The filling slurry prepared from the tailings of the tailing pond shows roughly the same change trend as the above slurry, but the change law is not obvious, which cannot be expressed by one kind of functional model, and the initial setting time and final setting time are less than the above slurry, which is because the tailings of the tailing pond contain more fine particles, which play a role in delaying setting in the slurry. For example, for five kinds of filling materials with different aggregates of 4:1, 6:1, 8:1, 12:1, and 20:1 sand-to-ash ratios and concentrations of 66%–72%, the initial setting times of filling slurry prepared from tailings of filling plant and tailings of tailing pond were 75.3 h–112.3 h, 77.6 h–122.2 h, and the final setting times were 82.8 h–123.4 h, 85.5 h–133.9 h. Therefore, it shows that the use of filling plant tailings containing fewer fine particles to prepare filling slurry can obtain a better treatment effect of the mining area, and the shortening of the solidification and hardening process of filling slurry can accelerate the mining cycle operation, and increase the amount of solid waste disposal per unit time, thus creating the necessary technical conditions for the enterprise to improve production efficiency and sustainable development.

BackgroundCuproptosis is a novel form of programmed cell death that differs from other types such as pyroptosis, ferroptosis, and autophagy. It is a promising new target for cancer therapy. Additionally, immune-related genes play a crucial role in cancer progression and patient prognosis. Therefore, our study aimed to create a survival prediction model for lung adenocarcinoma patients based on cuproptosis and immune-related genes. This model can be utilized to enhance personalized treatment for patients.MethodsRNA sequencing (RNA-seq) data of lung adenocarcinoma (LUAD) patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The levels of immune cell infiltration in the GSE68465 cohort were determined using gene set variation analysis (GSVA), and immune-related genes (IRGs) were identified using weighted gene coexpression network analysis (WGCNA). Additionally, cuproptosis-related genes (CRGs) were identified using unsupervised clustering. Univariate COX regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were performed to develop a risk prognostic model for cuproptosis and immune-related genes (CIRGs), which was subsequently validated. Various algorithms were utilized to explore the relationship between risk scores and immune infiltration levels, and model genes were analyzed based on single-cell sequencing. Finally, the expression of signature genes was confirmed through quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC), and Western blotting (WB).ResultsWe have identified 5 Oncogenic Driver Genes namely CD79B, PEBP1, PTK2B, STXBP1, and ZNF671, and developed proportional hazards regression models. The results of the study indicate significantly reduced survival rates in both the training and validation sets among the high-risk group. Additionally, the high-risk group displayed lower levels of immune cell infiltration and expression of immune checkpoint compared to the low-risk group.

Attaining agricultural sustainability and eliminating poverty are the key challenges of rural areas. Non-farm income diversification is a vital livelihood strategy that endorses sustainable agriculture and alleviates poverty. Considering the land degradation and poor economic situation of Pakistan's rain-fed areas, the current research examined the potential effects of non-farm income diversification on household poverty and adopting soil and water conservation (SWC) technologies. A survey of 441 farmers was conducted in rain-fed areas of Punjab, Pakistan, and for econometric analysis, the propensity score matching (PSM) technique was employed to explore the objectives. The results signified that diversified farmers were more likely to adopt SWC practices and were less vulnerable to poverty. The findings suggest that farmer-based organizations and agricultural extension activities must be strengthened as they support non-farm income diversification, thus facilitating investment in soil and water conservation technologies and reducing poverty.

IntroductionAnxiety not only harms employees’ work efficiency and satisfaction but also presents as a hazard to their mental health. This study aimed to investigate the prevalence of anxiety among Chinese employees, identify their personality profiles and explore the anxiety-related factors in different personality profiles.MethodsThis national investigation adopted the multistage random sampling method to recruit employees. A total of 3,875 employees were enrolled in this study, and 39.1% (1,515/3,875) of them were experiencing anxiety at the time of the study. Latent profile analysis (LPA) was conducted to identify personality subgroups among Chinese employees based on their BFI-10 scores.ResultsLPA identified a three-profile solution among Chinese employees: average, resilient, and introverted. Employees in the resilient profile had the lowest anxiety rate (16.1%, 132/822), and those in the average profile had the highest rate (46.8%, 1,166/2,494). Multivariate analysis results showed that for all personality profiles, self-efficacy was positively associated with anxiety, and work-family conflict was negatively associated with anxiety. High levels of perceived social support and self-efficacy reduced the risk of anxiety and higher work-family conflict and no partner increased the odds of anxiety in the average profile. For the introverted profile, female gender, and living in a city increased the chances of suffering from anxiety.DiscussionThis study identified that each personality profile of Chinese employees had its own set of factors associated with anxiety, which could facilitate employers to provide targeted interventions to alleviate employees’ anxiety.

BackgroundBrain metastases (BMs) are the most common central nervous system (CNS) malignant tumors, with rapid disease progression and extremely poor prognosis. The heterogeneity between primary lung cancers and BMs leads to the divergent efficacy of the adjuvant therapy response to primary tumors and BMs. However, the extent of heterogeneity between primary lung cancers and BMs, and the evolutionary process remains little known.MethodsTo deeply insight into the extent of inter-tumor heterogeneity at a single-patient level and the process of these evolutions, we retrospectively analyzed a total of 26 tumor samples from 10 patients with matched primary lung cancers and BMs. One patient underwent four times brain metastatic lesion surgery with diverse locations and one operation for the primary lesion. The genomic and immune heterogeneity between primary lung cancers and BMs were evaluated by utilizing whole-exome sequencing (WESeq) and immunohistochemical analysis.ResultsIn addition to inheriting genomic phenotype and molecular phenotype from the primary lung cancers, massive unique genomic phenotype and molecular phenotype were also observed in BMs, which revealed unimaginable complexity of tumor evolution and extensive heterogeneity among lesions at a single-patient level. By analysis of a multi-metastases case (Case 3) of cancer cells’ subclonal composition, we found similar multiple subclonal clusters in the four spatial and temporal isolated brain metastatic focus, with the characteristics of polyclonal dissemination. Our study also verified that the expression level of immune checkpoints-related molecule Programmed Death-Ligand 1 (PD-L1) (P = 0.0002) and the density of tumor-infiltrating lymphocytes (TILs) (P = 0.0248) in BMs were significantly lower than that in paired primary lung cancers. Additionally, tumor microvascular density (MVD) also differed between primary tumors and paired BMs, indicating that temporal and spatial diversity profoundly contributes to the evolution of BMs heterogeneity.ConclusionOur study revealed the significance of temporal and spatial factors to the evolution of tumor heterogeneity by multi-dimensional analysis of matched primary lung cancers and BMs, which also provided novel insight for formulating individualized treatment strategies for BMs.

IntroductionCuproptosis is a novel copper-dependent regulatory cell death (RCD), which is closely related to the occurrence and development of multiple cancers. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of colon adenocarcinoma (COAD) remains unclear.MethodsTranscriptome, somatic mutation, somatic copy number alteration and the corresponding clinicopathological data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Difference, survival and correlation analyses were conducted to evaluate the characteristics of CRGs in COAD patients. Consensus unsupervised clustering analysis of CRGs expression profile was used to classify patients into different cuproptosis molecular and gene subtypes. TME characteristics of different molecular subtypes were investigated by using Gene set variation analysis (GSVA) and single sample gene set enrichment analysis (ssGSEA). Next, CRG Risk scoring system was constructed by applying logistic least absolute shrinkage and selection operator (LASSO) cox regression analysis and multivariate cox analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to exam the expression of key Risk scoring genes.ResultsOur study indicated that CRGs had relatively common genetic and transcriptional variations in COAD tissues. We identified three cuproptosis molecular subtypes and three gene subtypes based on CRGs expression profile and prognostic differentially expressed genes (DEGs) expression profile, and found that changes in multilayer CRGs were closely related to the clinical characteristics, overall survival (OS), different signaling pathways, and immune cell infiltration of TME. CRG Risk scoring system was constructed according to the expression of 7 key cuproptosis-related risk genes (GLS, NOX1, HOXC6, TNNT1, GLS, HOXC6 and PLA2G12B). RT-qPCR and IHC indicated that the expression of GLS, NOX1, HOXC6, TNNT1 and PLA2G12B were up-regulated in tumor tissues, compared with those in normal tissues, and all of GLS, HOXC6, NOX1 and PLA2G12B were closely related with patient survival. In addition, high CRG risk scores were significantly associated with high microsatellite instability (MSI-H), tumor mutation burden (TMB), cancer stem cell (CSC) indices, stromal and immune scores in TME, drug susceptibility, as well as patient survival. Finally, a highly accurate nomogram was constructed to promote the clinical application of the CRG Risk scoring system.DiscussionOur comprehensive analysis showed that CRGs were greatly associated with TME, clinicopathological characteristics, and prognosis of patient with COAD. These findings may promote our understanding of CRGs in COAD, providing new insights for physicians to predict prognosis and develop more precise and individualized therapy strategies.

From national development to daily life, electric energy is integral to people’s lives. Although the development of electricity should be expected, expansion without restriction will only result in energy waste. The forecasting of electricity load plays an important role in the adjustment of power enterprises’ strategies and the stability of power operation. Recently, the electricity-related data acquisition system has been perfected, and the available load information has gradually reached the minute level. This means that the related load series lengthens and the time and spatial information of load become increasingly complex. In this paper, a load forecasting model based on multilayer dilated long and short-term memory neural network is established. The model uses a multilayer dilated structure to extract load information from long series and to extract information from different dimensions. Moreover, the attention mechanism is used to make the model pay closer attention to the key information in the series as an intermediate variable. Such structures can greatly alleviate the loss in the extraction of long time series information and make use of more valid historical information for future load forecasting. The proposed model is validated using two real datasets. According to load forecasting curves, error curve, and related indices, the proposed method is more accurate and stable in electricity load forecasting than the comparison methods.

The Late Triassic Carnian Pluvial Episode (CPE; ca. 234–232 Ma) was characterized by dramatic global temperature and humidity increases, which in many terrestrial settings was accompanied by changes from arid to humid vegetation types. This study reviews current evidence of terrestrial floral composition and distribution during the CPE and analyzes spatial and temporal variation with relation to potential environmental driving mechanisms. Available evidence suggests the CPE was a globally significant event that triggered significant increases in the abundance of ferns and hygrophytes in terrestrial floras and freshwater algae in fluvial and lacustrine settings. These changes ended a long interval of relatively arid terrestrial climatic conditions since the Early Triassic and are linked temporally with eruptions of the oceanic plateau Wrangellia Large Igneous Province (LIP). The massive release of greenhouse gasses including isotopically light CO2 during 3–4 distinct pulses of Wrangellia volcanism appears to have been the main driver of CPE climate change. Each pulse enhanced global atmospheric circulation and the hydrological cycle and resulted in changes from arid to humid conditions that affected floral abundance and composition. Higher terrestrial primary productivity in humid phases facilitated increased burial of terrestrial organic carbon and led to the recommencement of peat accumulation, ending the coal gap that had persisted since the Earliest Triassic times. Enhanced movement of carbon from the atmosphere through the biosphere into the geosphere may have counteracted the warming effects of Wrangellia volcanic greenhouse gas emissions and ultimately led to the return of a steady climate state that terminated the warm and humid conditions of the CPE.

ObjectiveInfluenza B virus (IBV) is highly contagious, spreads rapidly, and causes seasonal epidemic respiratory disease in the human population, especially in immunocompromised people and young children. Clinical manifestations in this high-risk population are often more severe than in immunocompetent hosts and sometimes atypical. Therefore, rapid, and accurate detection of IBV is important.MethodsAn amplified luminescent proximity homogeneous assay linked immunosorbent assay (AlphaLISA) was developed for detection of IBV by optimizing the ratio of IBV antibody-labeled receptor beads, streptavidin-conjugated donor beads and biotinylated IBV antibody, as well as the optimal temperature and time conditions for incubation. Assay sensitivity, specificity and reproducibility were evaluated. A total of 228 throat swab samples and inactivated influenza B virus were tested by AlphaLISA and lateral flow colloidal gold-based immunoassay (LFIA).ResultsAlphaLISA produced the best results for detection of inactivated influenza B virus when IBV antibody-labeled acceptor beads were 50 μg/ mL, streptavidin-conjugated donor beads were 40 μg/mL, and biotinylated IBV antibody was 0.5 μg/mL at 37°C for 15–10 min. Under these conditions, AlphaLISA had a limit of detection of 0.24 ng/mL for the detection of influenza B nucleoprotein, did not cross react with other common respiratory viruses, and showed good reproducibility with inter-assay coefficient of variation (CV) and intra-assay CV

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes’ mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.

ObjectiveTo investigate the predictive value of contrast-enhanced computed tomography (CECT) imaging features and clinical factors in identifying the macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) preoperatively.MethodsThis retrospective study included 101 consecutive patients with pathology-proven HCC (35 MTM subtype vs. 66 non-MTM subtype) who underwent liver surgery and preoperative CECT scans from January 2017 to November 2021. The imaging features were evaluated by two board-certified abdominal radiologists independently. The clinical characteristics and imaging findings were compared between the MTM and non-MTM subtypes. Univariate and multivariate logistic regression analyses were performed to investigate the association of clinical-radiological variables and MTM-HCCs and develop a predictive model. Subgroup analysis was also performed in BCLC 0-A stage patients. Receiver operating characteristic (ROC) curves analysis was used to determine the optimal cutoff values and the area under the curve (AUC) was employed to evaluate predictive performance.ResultsIntratumor hypoenhancement (odds ratio [OR] = 2.724; 95% confidence interval [CI]: 1.033, 7.467; p = .045), tumors without enhancing capsules (OR = 3.274; 95% CI: 1.209, 9.755; p = .03), high serum alpha-fetoprotein (AFP) (≥ 228 ng/mL, OR = 4.101; 95% CI: 1.523, 11.722; p = .006) and high hemoglobin (≥ 130.5 g/L; OR = 3.943; 95% CI: 1.466, 11.710; p = .009) were independent predictors for MTM-HCCs. The clinical-radiologic (CR) model showed the best predictive performance, achieving an AUC of 0.793, sensitivity of 62.9% and specificity of 81.8%. The CR model also effectively identify MTM-HCCs in early-stage (BCLC 0-A stage) patients.ConclusionCombining CECT imaging features and clinical characteristics is an effective method for preoperatively identifying MTM-HCCs, even in early-stage patients. The CR model has high predictive performance and could potentially help guide decision-making regarding aggressive therapies in MTM-HCC patients.

Mild behavioral impairment (MBI) is a neurobehavioral syndrome that occurs in the absence of cognitive impairment later in life (≥50 years of age). MBI is widespread in the pre-dementia stage and is closely associated with the progression of cognitive impairment, reflecting the neurobehavioral axis of pre-dementia risk states and complementing the traditional neurocognitive axis. Despite being the most common type of dementia, Alzheimer’s disease (AD) does not yet have an effective treatment; therefore, early recognition and intervention are crucial. The Mild Behavioral Impairment Checklist is an effective tool for identifying MBI cases and helps identify people at risk of developing dementia. However, because the concept of MBI is still quite new, the overall understanding of it is relatively insufficient, especially in AD. Therefore, this review examines the current evidence from cognitive function, neuroimaging, and neuropathology that suggests the potential use of MBI as a risk indicator in preclinical AD.

IntroductionProbiotics play critical roles in relieving inflammatory bowel disease (IBD). However, the underlying mechanism of Bacteroides fragilis strain ZY-312 (B. fragilis) for colonic mucosa regeneration in IBD remains unclear.MethodsThe weight loss, disease activity index (DAI), colon length, and histopathology-associated index (HAI) were evaluated the therapeutic effects of B. fragilis in a DSS-induced colitis mouse model. Colonic mucosa proliferation and apoptosis level, and mucus density were detected by histological stain. Gut microbiota was sequenced by 16srRNA analysis. The expression of signal transducer and activator of transcription 3 (STAT3) phosphorylation in colonic mucosa was detected in B. fragilis-treated mice in colitis. B. fragilis-regulated immunity factors of motivating downstream STAT3 phosphorylation were screened by ELISA and flow cytometry. Lastly, B. fragilis-mediated colonic mucosa regeneration effects were verified though the knockout of STAT3 (Stat3△IEC) and IL-22 (IL-22-/-) in mice, and inhibitor of STAT3 and IL-22 in co-culture model.ResultsB. fragilis alleviated DSS-induced colitis in mice with less weight loss, DAI, colon length shortening, and HAI. Further the results showed that B. fragilis motivated STAT3 phosphorylation in colonic mucosa with the upregulation of proliferation index Ki-67 and mucus density, the downregulation of apoptosis level, and the modulation of gut microbiota through a Stat3△IEC mice model and STAT3 inhibitor-added model in vitro. Meanhwhile we found that B. fragilis promoted IL-22 production, and increased the percentage of IL-22-secreting type 3 innate lymphocytes (ILC3) in colitis. Consequently, We identified that B. fragilis did not increase the expression of pSTAT3, either proliferation level, mucus density, or alter gut microbiota in IL-22-/- mice.DiscussionB. fragilis may indirectly motivate ILC3 to secrete IL-22, followed by IL-22-induced STAT3 phosphorylation, hence promoting colonic mucosa regeneration in colitis. It indicates that B. fragilis has the potential to be a biological agent for IBD therapy.

This study investigates the use of self-produced solid waste in mines to backfill the goaf, with energy saving and emission reduction technology requirements. Using a relevant backfill mixing proportion test and mechanical property test, we analyzed the strength variation law of backfill materials under different concentrations and cementation powder addition. The results showed that, for backfill materials at 7 days with an ash-tailings ratio of 1:6, the strength of specimens with 52% and 49% prepared concentrations, respectively, increased by 1.361 and 1.266 times over specimens with 49% and 46% concentrations. For backfill materials with 49% prepared concentrations and ash-tailings ratios of 1:6, 1:9, and 1:12, the specimen strength of the backfill materials with ratios of 1:6 and 1:9 improved by 0.616 MPa and 0.321 MPa—109.28% and 114.6%, respectively—compared with 1:9 and 1:12 backfill materials at 60 days. It is thus evident that the quantity of binding materials added plays a critical function in improving the strength of backfill materials, and in the subsequent application of goaf backfill. The strength of backfill materials can be enhanced by improving the gradation of backfill aggregates and increasing the amount of binding materials so as to achieve cost reductions and sustainable development.

The Yumu Shan is located at the northern margin of the Tibetan Plateau in northwest China. It is characterized by the development of several northeastward-protruding arcuate geomorphic bulge belts on its north slope. These bulge belts are distributed along the Wutongquan spring, the ancient Camel City, and the Xiaogengzi area, and south to Gaotai City in the Hexi Corridor. In this study, our detailed field mapping and structural analysis reveal northeastward active anticline folding along the curved bulge belts and related lacustrine sediments in their hinterlands. Radiocarbon dating of plant charcoal samples from lacustrine sedimentary layers yields a 14C age of AD 178 ± 42. This age is close to the time of the 180AD/Ms7.5 earthquake at Biaoshi City (i.e., the ancient Zhangye City) during the Eastern Han Dynasty. The similarity between seismic events and sedimentary age leads us to infer that the charcoal in the lacustrine layer records a major flood event related to the Biaoshi earthquake. We propose a fault-related fold model for the formation of the arcuate bulge belts and related sediments. First, a series of historical earthquake activities in the Holocene, especially the 180AD/Ms7.5 Biaoshi earthquake, may have led to active blind thrust faulting in the northern margin of the plateau. Then, blind thrusting may have resulted in fault-related anticline folding, causing the formation of geomorphic bulges. The latter acts as a flood-retaining dam, resulting in hinterland deposition of lacustrine sediments. For this reason, we suggest that seismogenic blind thrust faulting is responsible for the uplift and northward growth of the Tibetan Plateau. As the northernmost blind thrust in this area, the Xiaogengzi Fault could be considered the North Boundary Thrust (NBT), which defines exactly the northern margin of the plateau.

ObjectiveThe aim of this study was to design and optimize a cold atmospheric plasma (CAP) device that could be applied in an oral environment and to study its effects on plaque biofilm metabolism and regrowth, as well as microbial flora composition and enamel demineralization.MethodCAP was obtained through a dielectric barrier discharge device; the optical properties were analyzed using emission spectroscopy. The electrochemical analysis of plasma devices includes voltametric characteristic curves and Lissajous. The Streptococcus mutans (UA159) and saliva biofilms were treated in vitro, and the effects of CAP on biofilm metabolism were investigated using MTT and lactate dehydrogenase assays. The duration of antibacterial activity on biofilms was examined, scanning electron microscopy was used to observe the morphology of biofilms, and 16S rRNA sequencing was used to explore the influence of CAP on the microbial flora composition of saliva biofilms. An in vitro model of biofilm-enamel demineralization was designed, and the effect of CAP on enamel demineralization was evaluated by micro surface hardness and micro-CT analysis.ResultsCAP had antibacterial proliferative ability toward Streptococcus mutans biofilms and saliva biofilms and was stronger than ultraviolet under the same tested conditions. After 24 h, the antibacterial effect disappeared, which proved the short-term timeliness of its bactericidal ability. CAP can inhibit the acid production of biofilms, and its inhibitory effect on saliva biofilms can be extended to 24 h. CAP had a strong ability to regulate the composition of plaque biofilms, especially for Lactococcus proliferation, a major acid-producing bacterium in microcosm biofilms. The CAP-treated enamels were more acid-tolerant than non-treated controls.ConclusionCAP had an explicit bactericidal effect on caries-related biofilms, which is a short-term antibacterial effect. It can inhibit the acid production of biofilms and has a downregulation effect on Lactococcus in saliva biofilms. CAP can help reduce demineralization of enamel.

Circular RNAs (circRNAs), as endogenous non-coding RNA with unique closed ring structure, is closely related to animal reproduction, and understanding the expression of circRNA in yak and cattleyak epididymal tissues is of great significance for understanding cattleyak sterility. Based on this, we screened and identified the differentially expressed circRNA in the epididymis of three yaks and two cattleyak. A total of 1,298 circRNAs were identified in the epididymis of yak and cattleyak, of which 137 differentially expressed (DE) circRNAs and the functions of some of them were elucidated in this research, as well as qPCR verification to 6 circRNAs from the 137 DE circRNAs. Gene Ontology (GO) enrichment analysis suggested that DE circRNAs were mainly related to metabolic process, development process, immune system process, reproductive process, reproduction, biological adhesion and growth. COG classification analysis showed that the DE circRNAs derived genes were mainly related to replication, recombination and repair. KEGG pathway analysis suggested that DE circRNAs were mainly involved in RNA degradation. In addition, we also screened Bta-mir-103, which is a circRNA binding miRNA related to sperm activity.

Neoadjuvant systemic therapy (NST) is widely applied in breast cancer treatment, but individuals respond differently to the same NST regimen. It is unclear which patients should adjust their NST regimen and what such an adjustment should be, especially for patients with radiologically partial response (PR). This study aimed to identify a quantitative efficacy evaluation index to evaluate the therapeutic effect of NST. 164 patients were enrolled in this study received four cycles of epirubicin and cyclophosphamide (EC), followed by four cycles of taxanes with trastuzumab [T(H)], if needed. Of patients with a volume change rate of EC treatment (δV1) below 0.80, more than half benefited from subsequent T(H) treatment compared with EC treatment. Importantly, for δV1 of 0.80 and higher, patients’ subsequent T(H) treatment was not as efficient as previous EC treatment and they have a lower pathological complete response (pCR) rate. Across all patients, nanoparticle albumin-bound paclitaxel had a numerically higher pCR rate over other taxanes in patients with triple-negative breast cancer. This study showed that the volume change rate is better than the diameter change rate in monitoring the therapeutic effect of NST. Furthermore, δV1 is a good quantitative efficacy evaluation index to distinguish patients resistant to EC treatment and predict the pCR rate and guide the adjustment of individualized NST regimens.

Introduction: Parkinson’s disease and type 2 diabetes have both elements of local amyloid depositions in their pathogenesis. In Parkinson’s disease, alpha-synuclein (aSyn) forms insoluble Lewy bodies and Lewy neurites in brain neurons, and in type 2 diabetes, islet amyloid polypeptide (IAPP) comprises the amyloid in the islets of Langerhans. In this study, we assessed the interaction between aSyn and IAPP in human pancreatic tissues, both ex vivo and in vitro.Material and Methods: The antibody-based detection techniques, proximity ligation assay (PLA), and immuno-TEM were used for co-localization studies. Bifluorescence complementation (BiFC) was used for interaction studies between IAPP and aSyn in HEK 293 cells. The Thioflavin T assay was used for studies of cross-seeding between IAPP and aSyn. ASyn was downregulated with siRNA, and insulin secretion was monitored using TIRF microscopy.Results: We demonstrate intracellular co-localization of aSyn with IAPP, while aSyn is absent in the extracellular amyloid deposits. ASyn reactivity is present in the secretory granules of β-cells and some α-cells in human islets. The BiFC-expression of aSyn/aSyn and IAPP/IAPP in HEK293 cells resulted in 29.3% and 19.7% fluorescent cells, respectively, while aSyn/IAPP co-expression resulted in ∼10% fluorescent cells. Preformed aSyn fibrils seeded IAPP fibril formation in vitro, but adding preformed IAPP seeds to aSyn did not change aSyn fibrillation. In addition, mixing monomeric aSyn with monomeric IAPP did not affect IAPP fibril formation. Finally, the knockdown of endogenous aSyn did not affect β cell function or viability, nor did overexpression of aSyn affect β cell viability.Discussion: Despite the proximity of aSyn and IAPP in β-cells and the detected capacity of preformed aSyn fibrils to seed IAPP in vitro, it is still an open question if an interaction between the two molecules is of pathogenic significance for type 2 diabetes.

Background: Individualized recurrence risk prediction in patients with stage II/III colorectal cancer (CRC) is crucial for making postoperative treatment decisions. However, there is still a lack of effective approaches for identifying patients with stage II and III CRC at a high risk of recurrence. In this study, we aimed to establish a credible gene model for improving the risk assessment of patients with stage II/III CRC.Methods: Recurrence-free survival (RFS)-related genes were screened using Univariate Cox regression analysis in GSE17538, GSE39582, and GSE161158 cohorts. Common prognostic genes were identified by Venn diagram and subsequently subjected to least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis for signature construction. Kaplan-Meier (K-M), calibration, and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy and superiority of our risk model. Single-sample gene set enrichment analysis (ssGSEA) was employed to investigate the relationship between the infiltrative abundances of immune cells and risk scores. Genes significantly associated with the risk scores were identified to explore the biological implications of the 9-gene signature.Results: Survival analysis identified 347 RFS-related genes. Using these genes, a 9-gene signature was constructed, which was composed of MRPL41, FGD3, RBM38, SPINK1, DKK1, GAL3ST4, INHBB, CTB-113P19.1, and FAM214B. K-M curves verified the survival differences between the low- and high-risk groups classified by the 9-gene signature. The area under the curve (AUC) values of this signature were close to or no less than the previously reported prognostic signatures and clinical factors, suggesting that this model could provide improved RFS prediction. The ssGSEA algorithm estimated that eight immune cells, including regulatory T cells, were aberrantly infiltrated in the high-risk group. Furthermore, the signature was associated with multiple oncogenic pathways, including cell adhesion and angiogenesis.Conclusion: A novel RFS prediction model for patients with stage II/III CRC was constructed using multicohort validation. The proposed signature may help clinicians better manage patients with stage II/III CRC.

Radiation-induced intestinal injury is characterized by intestinal barrier impairment. However, the therapeutic effects of probiotics for intestinal epithelial barrier repair in a mouse model of radiation-induced intestinal injury remain unclear. Previously, we isolated a strain of Bacteroides fragilis from the feces of a healthy infant and named it as B. fragilis strain ZY-312 (B. fragilis). In this study, we showed that B. fragilis can ameliorate radiation-induced intestinal injury in mice, manifested by decreased weight loss, intestinal length shortening, and intestinal epithelial cell (IEC) shedding. Moreover, we found that B. fragilis promoted IEC proliferation, stem cell regeneration, mucus secretion, and tight junction integrity by upregulating the STAT3 signaling pathway, through an experimental verification in Stat3△IEC mice (STAT3 defects in intestinal epithelial cells). Thus, the underlying protective mechanism of B. fragilis in radiation-induced intestinal injury is related to IEC proliferation, stem cell regeneration, goblet cell secretion, and tight junction repair via activation of the STAT3 signaling pathway. In addition, the therapeutic effects of B. fragilis were studied to provide new insights into its application as a functional and clinical drug for radiation-induced intestinal injury after radiotherapy.

ObjectiveTo evaluate the economics of sugemalimab plus chemotherapy in the first-line treatment of metastatic non-small cell lung cancer, and to provide a reference for the formulation of relevant medical insurance policies and rational drug use.MethodsFrom the perspective of the Chinese health system, a three-state partitioned survival model was constructed based on data from a phase III randomized clinical trial (GEMSTONE 302) to evaluate the cost-utility of sugemalimab plus chemotherapy compared with chemotherapy in first-line treatment of metastatic non-small cell lung cancer. Model results were expressed as total cost, life years, quality-adjusted life years, and incremental cost-effectiveness ratio. The robustness of the underlying analysis results was verified using one-way sensitivity analysis and probabilistic sensitivity analysis.ResultsThe results of the base-case analysis showed that sugemalimab plus chemotherapy yielded 1.63 QALYs at a total cost of 130,667.70 USD, chemotherapy yielded 1.04 QALYs at a total cost of 64,001.02 USD, and the ICER was 113,155.52 USD/QALY, which was well above the current willingness-to-pay threshold in China (3 times 2021 per capita GDP) (36,203.88 USD).ConclusionThis study suggests that sugemalimab in combination with a chemotherapy regimen is more effective but not economical for patients with metastatic non-small cell lung cancer receiving first-line therapy in China and that a reasonable reduction in drug prices could improve the probability of it being economical.

IntroductionGut microbiota plays a crucial role in the development and progression of nonalcoholic steatohepatitis (NASH) and associated hepatocellular carcinoma (HCC). Akkermansia muciniphila was reported to inhibit inflammation-associated cancer in the intestine. The anti-NASH ability of A. muciniphila has recently been found. Thus, we were to investigate whether supplementation of A. muciniphila could prevent NASH-associated HCC.MethodsIn a model we called STAM, male C57BL/6J mice were subcutaneously injected with 200 µg streptozotocin at 4 days after birth, and fed with high-fat diet at 4 weeks of age to induce NASH-associated HCC. Faeces from mice and patients with NASH-related HCC were collected for 16S rRNA sequencing. STAM mice were orally administered either saline or A. muciniphila twice a day starting at 4 or 10 weeks of age. The effects of A. muciniphila on the immune responses were also evaluated.ResultsPatients and mice with NASH-related HCC showed significantly reduced gut A. muciniphila in comparison to healthy controls. Administration of breast milk-isolated A. muciniphila (AM06) but not feces-isolated A. muciniphila (AM02) could improve NASH severity. Interestingly, breast milk-isolated A. muciniphila treatment suppressed the progression of NASH to HCC, accompanied with an increased hepatic CXCR6+ natural killer T (NKT) cell and decreased macrophage infiltration. The antitumor ability of A. muciniphila was not evident in NKT cell-deficient mice (CD1d-/- and CXCR6-/-). In vitro, A. muciniphila promoted the killing of hepG2 cells by NKT cells.DiscussionOur study will provide the rationale for the application of A. muciniphila to treat NASH and for the prevention of its progression to HCC.

Neurotrophic tyrosine receptor kinase (NTRK) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, NTRK rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel NTRK2 rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), reverse transcriptase PCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between NTRK2 and the lipoma HMGIC fusion partner-like 3 (LHFPL3). This oncogenic gene rearrangement involves 5’ LHFPL3 and 3’ NTRK2, retaining the entire tyrosine kinase domain of NTRK2 genes. Moreover, the targeted DNA NGS analysis revealed an IDH1 (p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of the LHFPL3::NTRK2 in this case likely involves aberrant dimerization and constitutive activation of RTK signaling pathways.