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ABSTRACT Background Gastric adenocarcinoma of the fundic gland type (GA‐FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features. Methods We performed whole‐genome sequencing (WGS) in formalin‐fixed paraffin‐embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA‐FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA‐FG disease. Results We characterized the genomic architecture of GA‐FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored “Kataegis.” Distinct genomic alterations between GA‐FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non‐silent alterations of formerly well‐known drivers such as TP53, PIK3CA and KRAS were identified in GA‐FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA‐FG and conventional gastric cancer. Conclusion Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA‐FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.

Abstract Amid the escalating global climatic challenges, hydrological risks significantly influence human settlement patterns, underscoring the imperative for an in-depth comprehension of hydrological change’s ramifications on human migration. However, predominant research has been circumscribed to the national level. The study delves into the nonlinear effects of hydrological risks on migration dynamics in 46,776 global subnational units. Meanwhile, leveraging remote sensing, we procured globally consistent metrics of hydrological intrusion exposure, offering a holistic risk assessment encompassing hazard, exposure, and vulnerability dimensions, thus complementing previous work. Here, we show that exposure is the primary migration driver, surpassing socioeconomic factors. Surrounding disparities further intensified exposure’s impact. Vulnerable groups, especially the economically disadvantaged and elderly, tend to remain in high-risk areas, with the former predominantly migrating within proximate vicinities. The nonlinear analysis delineates an S-shaped trajectory for hydrological exposure, transitioning from resistance to migration and culminating in entrapment, revealing dependence on settlement resilience and adaptability.

Abstract Background Metabolic reprogramming and epigenetic alterations contribute to the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). Lactate-dependent histone modification is a new type of histone mark, which links glycolysis metabolite to the epigenetic process of lactylation. However, the role of histone lactylation in PDAC remains unclear. Methods The level of histone lactylation in PDAC was identified by western blot and immunohistochemistry, and its relationship with the overall survival was evaluated using a Kaplan-Meier survival plot. The participation of histone lactylation in the growth and progression of PDAC was confirmed through inhibition of histone lactylation by glycolysis inhibitors or lactate dehydrogenase A (LDHA) knockdown both in vitro and in vivo. The potential writers and erasers of histone lactylation in PDAC were identified by western blot and functional experiments. The potential target genes of H3K18 lactylation (H3K18la) were screened by CUT&Tag and RNA-seq analyses. The candidate target genes TTK protein kinase (TTK) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were validated through ChIP-qPCR, RT-qPCR and western blot analyses. Next, the effects of these two genes in PDAC were confirmed by knockdown or overexpression. The interaction between TTK and LDHA was identified by Co-IP assay. Results Histone lactylation, especially H3K18la level was elevated in PDAC, and the high level of H3K18la was associated with poor prognosis. The suppression of glycolytic activity by different kinds of inhibitors or LDHA knockdown contributed to the anti-tumor effects of PDAC in vitro and in vivo. E1A binding protein p300 (P300) and histone deacetylase 2 were the potential writer and eraser of histone lactylation in PDAC cells, respectively. H3K18la was enriched at the promoters and activated the transcription of mitotic checkpoint regulators TTK and BUB1B. Interestingly, TTK and BUB1B could elevate the expression of P300 which in turn increased glycolysis. Moreover, TTK phosphorylated LDHA at tyrosine 239 (Y239) and activated LDHA, and subsequently upregulated lactate and H3K18la levels. Conclusions The glycolysis-H3K18la-TTK/BUB1B positive feedback loop exacerbates dysfunction in PDAC. These findings delivered a new exploration and significant inter-relationship between lactate metabolic reprogramming and epigenetic regulation, which might pave the way toward novel lactylation treatment strategies in PDAC therapy.

The deposition of Aβ42 has been regarded as one of the important pathological features of Alzheimer’s disease (AD). However, drug development for Aβ42 toxicity has been progressed slowly.

Objectives To evaluate changes in health outcomes between years 2 and 3 after discharge following COVID-19 and to identify risk factors for poor health 3-year post-discharge.Design This is a multicentre observational cohort study.Setting This study was conducted in two centres from Wuhan, China.Participants Eligibility screening has been performed in 3988 discharged laboratory-confirmed adult COVID-19 patients. Exclusion criteria were refusal to participate, inability to contact and death before follow-up. The WHO COVID-19 guidelines on defining disease severity were adopted.Results 1594 patients participated in the 1-year, 2-year and 3-year follow-ups, including 796 (49.9%) male patients, and 422 (26.5%) patients were classified in the severe disease group. 3 years after discharge, 182 (11.4%) patients still complained of at least one symptom. The most common symptoms were fatigue, myalgia, chest tightness, cough, anxiety, shortness of breath and expectoration. Fatigue or myalgia, the most common symptom cluster, frequently coexisted with chest symptoms and anxiety. Symptom persistence between years 2 and 3 was reported in 70 patients (4.4%) for which intensive care unit (ICU) admission was a risk factor (p=0.038). Of the 1586 patients who completed the chronic obstructive pulmonary disease assessment test (CAT), 97 (6.1%) scored ≥10, with older age being associated with CAT ≥10 (p=0.007).Conclusions Between years 2 and 3 after SARS-CoV-2 infection, most patients returned to an asymptomatic state, and only a few were still symptomatic. ICU admission was a risk factor for symptom persistence.

BackgroundTo determine the relationship between effort-reward imbalance (ERI) and quality of working life (QWL) among medical caregivers and the mediating role of job burnout.MethodsThis was a cross-sectional survey. A total of 787 medical caregivers at seven hospitals from Sichuan and Chongqing, China, between May to September 2023 were included in this observational study. The General Information Questionnaire, Effort-Reward Imbalance Questionnaire (ERI), Maslach Burnout Inventory-General Survey (MBI-GS), and Quality of Working Life Scale (QWL7-32) were used for data collection. SPSS 26.0 and PROCESSv3.3 were used for all data analyses, including descriptive statistics.ResultsA total of 820 questionnaires were distributed, of which only 787 were valid (return rate; 95.98%). The QWL score of medical caregivers was 126.94 ± 16.69. However, QWL scores were significantly different depending on age, number of children, family support status, department, years of experience, night shift status, number of night shifts per month, number of hours worked per day, monthly income, and occurrence of errors or adverse events (p

IntroductionChronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more).MethodsThirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network.ResultsThe differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia.DiscussionIn our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Abstract Background Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer-related deaths in men. Prostate-specific membrane antigen (PSMA) as a target has gained increasing attention. This research aims to investigate and understand how altering size of PEG impacts the in vitro and in vivo behavior and performance of PSMA inhibitors, with a specific focus on their pharmacokinetic characteristics and targeting properties. Results Two 68Ga-labeled PSMA-targeted radiotracers were developed, namely [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD, with varying sizes of polyethylene glycol (PEG). [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD had excellent affinity for PSMA with IC50 being 8.06 ± 0.91, 6.13 ± 0.79 nM, respectively. Both tracers enabled clear visualization of LNCaP tumors in PET images with excellent tumor-to-background contrast. They also revealed highly efficient uptake and internalization into LNCaP cells, increasing over time. The biodistribution studies demonstrated that both radioligands exhibited significant and specific uptake into LNCaP tumors. Furthermore, they were rapidly cleared through the renal pathway, as evidenced by [68Ga]Ga-PP4-WD and [68Ga]Ga-PP8-WD showing a tenfold and a fivefold less in renal uptake, respectively, compared to [68Ga]Ga-Flu-1 in 30 min. Both in vitro and in vivo experiments demonstrated that PEG size significantly impacted tumor-targeting and pharmacokinetic properties. Conclusions These radiotracers have demonstrated their effectiveness in significantly reducing kidney uptake while maintaining the absorbed dose in tumors. Both radiotracers exhibited strong binding and internalization characteristics in vitro, displayed high specificity and affinity for PSMA in vivo.

In plants, the lysine and histidine transporter (LHT) family represent a class of proteins that mediate the uptake, translocation, and utilization of amino acids. The tea plant (Camellia sinensis) is a perennial evergreen with a relatively high level of amino acids. However, systematic identification and molecular characterization of the LHT gene family has rarely been reported in tea plants. In this study, 22 CsLHTs were identified from the ‘Shuchazao’ genome and classified into two groups. The modeled three-dimensional structure and the conserved domains presented a high similarity among the LHTs proteins. Moreover, it was predicted that a few genes were conserved through the analysis of the physiochemical characters, structures and cis-elements in promoters. The expression patterns in tea plants revealed that CsLHT7 was mainly expressed in the roots, and CsLHT4 and CsLHT11 exhibited relatively high expression in both the roots and leaves. Moreover, the expression of all three genes could be induced by organic nitrogen. Additionally, heterogeneous expression of CsLHT4, CsLHT7 and CsLHT11 in Arabidopsis thaliana decreased the aerial parts biomass compared with that in WT plants while significantly increased the rosette biomass only for CsLHT11 transgenic plants versus WT plants. Overall, our results provide fundamental information about CsLHTs and potential genes in N utilization for further analysis in tea plants.

Abstract Traumatic brain injury (TBI) is a major cause of death and disability in adults. The pathological process of TBI involves a multifactorial cascade in which kinases have been proven contribute to interactions between relevant factors and amplification of signaling cascades. Cyclin-dependent kinase 5 (Cdk5) is a promising kinase that has been implicated in various brain disorders, including TBI. However, the mechanism by which Cdk5 induces neuronal damage remains unclear. Here, we show for the first time that Drosha, a key enzyme in microRNA biogenesis, is a pivotal substrate of abnormally activated Cdk5. Cdk5-mediated phosphorylation decreases Drosha expression and exacerbates nerve injury in TBI. We proved that maintaining Drosha expression via the administration of repurposed Cdk5 inhibitors that were previously studied in clinical trials is a promising approach for the early treatment of TBI. Together, our work identifies Drosha as a novel target for neuroprotective strategies after TBI and suggests Cdk5-mediated regulation of Drosha expression as a potential therapeutic strategy for early TBI intervention.

In this paper, a method for detection of crack locations and the width of basin insulators is proposed. Based on the optical frequency domain reflectometry (OFDR) system, the system utilizes an FBG with high feedback for strain as well as temperature, which is affixed to the surface of the tub insulator, and a common single-mode optical fiber, which is used for transmitting data and connected to the optical backscattering reflectometry interrogator. The interrogator measures the backscattered light from the FBG, which varies with temperature or strain. The method has been used to measure the location and width of several different cracks and can locate the crack position with a spatial resolution of 1 mm and measure the crack width with a resolution of 0.77 mm. The method has been used to measure the position and width of insulators. This method provides a simple and fast approach to crack detection in insulators.

Abstract Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF‐EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Medicinal food varieties developed according to the theory of medical and edible homologues are effective at preventing and treating chronic diseases and in health care. As of 2022, 110 types of traditional Chinese medicines from the same source of medicine and food have been published by the National Health Commission. Inflammation is the immune system’s first response to injury, infection, and stress. Chronic inflammation is closely related to many diseases such as atherosclerosis and cancer. Therefore, timely intervention for inflammation is the mainstay treatment for other complex diseases. However, some traditional anti-inflammatory drugs on the market are commonly associated with a number of adverse effects, which seriously affect the health and safety of patients. Therefore, the in-depth development of new safe, harmless, and effective anti-inflammatory drugs has become a hot topic of research and an urgent clinical need. Polysaccharides, one of the main active ingredients of medical and edible homologous traditional Chinese medicines (MEHTCMs), have been confirmed by a large number of studies to exert anti-inflammatory effects through multiple targets and are considered potential natural anti-inflammatory drugs. In addition, the structure of medical and edible homologous traditional Chinese medicines’ polysaccharides (MEHTCMPs) may be the key factor determining their anti-inflammatory activity, which makes the underlying the anti-inflammatory effects of polysaccharides and their structure–efficacy relationship hot topics of domestic and international research. However, due to the limitations of the current analytical techniques and tools, the structures have not been fully elucidated and the structure–efficacy relationship is relatively ambiguous, which are some of the difficulties in the process of developing and utilizing MEHTCMPs as novel anti-inflammatory drugs in the future. For this reason, this paper summarizes the potential anti-inflammatory mechanisms of MEHTCMPs, such as the regulation of the Toll-like receptor-related signaling pathway, MAPK signaling pathway, JAK-STAT signaling pathway, NLRP3 signaling pathway, PI3K-AKT signaling pathway, PPAR-γ signaling pathway, Nrf2-HO-1 signaling pathway, and the regulation of intestinal flora, and it systematically analyzes and evaluates the relationships between the anti-inflammatory activity of MEHTCMPs and their structures.

Low-heat Portland cement and ground granulated blast furnace slag are widely used for the preparation of hydraulic concrete. Nevertheless, the effect and mechanism of corrosion on low-heat Portland cement paste mixed with ground granulated blast furnace slag need to be further explored. This paper investigated the impact of ground granulated blast furnace slag on the calcium leaching of low-heat Portland cement paste by evaluating its mass loss, porosity, leaching depth, compressive strength, and Vickers hardness, and comparing it with the leaching performance of ordinary Portland cement paste. Furthermore, the phase composition and morphology of low-heat Portland cement paste containing ground granulated blast furnace slag were analyzed by X-ray diffraction, mercury intrusion porosimetry, and scanning electron microscopy. The results indicate that, after 180 days of soaking in ammonium chloride solution, the mass loss rate, growth rate of porosity, leaching depth, and compressive strength loss rate of low-heat Portland cement paste were 8.0%, 43.6%, 9.1 mm, and 27.7%, respectively, while those of ordinary Portland cement paste were 7.4%, 37.8%, 8.4 mm, and 30.1%, indicating that low-heat Portland cement paste is slightly more damaging than ordinary Portland cement. The addition of ground granulated blast furnace slag could significantly improve the leaching resistance of low-heat Portland cement. For instance, after adding 20% ground granulated blast furnace slag, the above test values were 2.4%, 28.5%, 5.6 mm, and 20.8%, respectively. The reason for this is that ground granulated blast furnace slag has the potential to reduce the porosity of low-heat Portland cement paste, and it can also undergo the secondary hydration reaction with its hydration product Ca(OH)2 to enhance the paste structure. Considering the cost performance, the suitable dosage of low-heat Portland cement paste for satisfactory leaching resistance is about 20%.

Odor compounds produced in salted egg yolk during thermal processing were identify by sensory evaluation and gas chromatography-mass spectrometry (GC-MS) combined with multivariate statistical analysis such as hierarchical cluster analysis (HCA), orthogonal partial least squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA). By using quantitative descriptive sensory analysis, it was found that there was a significant difference in the flavor profile between egg yolk samples with and without unpleasant odor, and it was determined that some egg yolks had obvious off-flavor during hot processing. Cluster analysis showed that the six groups of salted egg yolk samples were clearly divided into two categories, which was consistent with the sensory evaluation results. Furthermore, OPLS-DA identified 33 major differential components with variable importance in the projection (VIP) scores greater than one between samples with and without unpleasant odor, and aldehydes and alcohols were the most significant differential components. Finally, the volatile compounds showing a positive correlation with sour odor were screened by PCA, and n-hexanal, n-valeraldehyde, 1-octen-3-ol, trans,trans-2,4-decadienal, styrene, dimethyl disulfide and 2-nonone were identified due to their odor activity values (OAV) greater than one as the major odor compounds of salted egg yolk during thermal processing. The results provide a reference for analysis of the flavor characteristics and possible off-flavor components of salted egg yolk after thermal processing and provide a scientific basis for accessing the quality of salted egg yolk.

Control of premature corrosion of magnesium (Mg) alloy bioresorbable stents (BRS) is frequently achieved by the addition of rare earth elements. However, limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after. Herein, we report a “built-up” composite film consisting of a bottom layer of MgF2 conversion coating, a sandwich layer of a poly (1, 3-trimethylene carbonate) (PTMC) and 3-aminopropyl triethoxysilane (APTES) co-spray coating (PA) and on top a layer of poly (lactic-co-glycolic acid) (PLGA) ultrasonic spray coating to decorate the rare earth element-free Mg–2Zn–1Mn (ZM21) BRS for tailoring both corrosion resistance and biological functions. The developed “built-up” composite film shows synergistic functionalities, allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling. Of special importance is that the synergistic corrosion control effects of the “built-up” composite film allow for maintaining the mechanical integrity of stents for up to 3 months, where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries. Moreover, the functionalized ZM21 BRS accomplished re-endothelialization within one month.

Many attentions have been previously focused to identify the multiple biochemical components related to tea quality and health benefits, however, the natural variation of biochemical components present in tea germplasm has not been adequately evaluated. In this study, the main biochemical components, leaf morphological and yield characteristics were evaluated for four rounds of tea leaves in a panel of 87 elite tea cultivars suitable for black, green, or oolong tea. Significant variations were observed among the tea cultivars, as well as seasonal differences in the levels of the free amino acid (FAA), caffeine (CAF), tea polyphenols (TP), water extract (WE) and TP to FAA ratio (TP/FAA). Results showed that the average levels of FAA showed a seasonal change, with the highest level of 4.0% in the 1st spring tea in the cultivars suitable for green tea and the lowest of 3.2% in summer tea in the cultivars suitable for black tea. The average CAF content was highest 3.2% in the cultivars suitable for oolong tea in the 1st spring and the lowest 2.5% in the cultivars suitable for green tea in summer. Limited seasonal and varietal variations were noticed in the average levels of WE among the three categories of tea. In addition, significant natural variation of the morphological characteristics, bud length varying from 2.5 cm to 8.7 cm, bud density from 190.3 buds · m-2 to 1 730.3 buds · m-2, mature leaves biomass from 128.4 kg · hm-2 to 2 888.4 kg · hm-2, and yield component traits of 100 buds (one bud with two leaves) dry weight from 3.7 g to 37.7 g, tea yield/round from 444.6 kg · hm-2 to 905.3 kg · hm-2, were observed. The aim of our evaluation was not only to identify the advantages of seasonal and clonal variations but also to provide a new viewpoint for their further application. Representative accessions were selected from the germplasm to promote the establishment of an inherent biochemical constituent expressing the quality of black, green, and oolong tea. The findings might be utilized to establish early selection criteria to enhance the tea breeding and production program.

This paper introduces a novel method combining semantic contrast learning and event detection, employing an attention mechanism to compare and analyze semantic features between two distinct text types. We utilize a convolutional neural network to extract deep semantic information from texts, while the attention mechanism models global dependencies to elucidate complex semantic information. In event detection, we construct positive and negative samples using event-type labeling information, facilitating the differentiation of semantic spaces associated with various event types in text. We apply this methodology to a corpus relevant to vocational education English translation, aiming to extract and analyze stylistic features. Our results reveal distinct lexical characteristics; the Type Token Ratio (TTR) and Standardized Type Token Ratio (STTR) for the Statements are calculated at 25 and 45.08, respectively. In the analysis of high-frequency words within the English translation of the Report, nouns and adjectives are predominant, with counts of 4,466 and 1,962, respectively, surpassing those in the English translation of the Consultation. Syntactic feature analysis indicates that the overall trends in both text types are consistent; however, there is a notable variation in sentence length deviation, which increases from 1.47 to 3.36 in the Report and decreases from 2.49 to 2.31 in the Consultation. This differential analysis underscores the nuanced stylistic adaptations between the two translated text types.

Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD’s prognostic evaluation is controversial. Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD. Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle–Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity. Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient ( r ), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies. Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r , −0.28 (−0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity. Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho’s prognostic value.

This study reports an innovative approach for producing nanoplastics (NP) from various types of domestic waste plastics without the use of chemicals. The plastic materials used included water bottles, styrofoam plates, milk bottles, centrifuge tubes, to-go food boxes, and plastic bags, comprising polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE), and Poly (Ethylene-co-Methacrylic Acid) (PEMA). The chemical composition of these plastics was confirmed using Raman and FTIR spectroscopy, and they were found to have irregular shapes. The resulting NP particles ranged from 50 to 400 nm in size and demonstrated relative stability when suspended in water. To assess their impact, the study investigated the effects of these NP particulates on cell viability and the expression of genes involved in inflammation and oxidative stress using a macrophage cell line. The findings revealed that all types of NP reduced cell viability in a concentration-dependent manner. Notably, PS, HDPE, and PP induced significant reductions in cell viability at lower concentrations, compared to PEMA and PET. Moreover, exposure to NP led to differential alterations in the expression of inflammatory genes in the macrophage cell line. Overall, this study presents a viable method for producing NP from waste materials that closely resemble real-world NP. Furthermore, the toxicity studies demonstrated distinct cellular responses based on the composition of the NP, shedding light on the potential environmental and health impacts of these particles.

Based on in-situ vertical observations of volatile organic compounds (VOCs) in the lower troposphere (0–1.0 km) in Nanjing, China, during the summer and autumn, we analyzed the VOCs vertical profiles, diurnal variation, and their impact factors in meteorology and photochemistry. The results showed that almost all the concentrations of VOC species decreased with height, similar to the profiles of primary air pollutants, as expected. However, we found the ratios of inactive species (e.g., acetylene) and secondary VOCs (e.g., ketones and aldehydes) in total VOCs (TVOCs) increased with height. Combined with satellite-retrieved data, we found the average HCHO tropospheric column concentrations were 2.0 times higher in the summer than in the autumn. While the average of tropospheric NO2 column concentrations was 3.0 times lower in the summer than in the autumn, the seasonal differences in the ratio of oxygenated VOCs (OVOCs) to NO2 (e.g., HCHO/NO2) shown in TROPOMI satellite-retrieved data were consistent with in-situ observations (e.g., acetone/NO2). On average, during autumn daytime, the mixing layer (ML), stable boundary layer (SBL), and residual layer (RL) had OH loss rates (LOH) of 6.9, 6.3, and 5.5 s−1, respectively. The LOH of alkenes was the largest in the ML, while the LOH of aromatics was the largest in the SBL and RL. At autumn night, the NO3 loss rates (LNO3) in the SBL and RL were 2.0 × 10−2 and 1.6 × 10−2 s−1, respectively, and the LNO3 of aromatics was the largest in the SBL and RL. In the daytime of summer, the LOH of VOCs was ~40% lower than that in autumn in all layers, while there was no significant difference in LNO3 at night between the two seasons. This study provides data support and a theoretical basis for VOC composite pollution control in the Nanjing region.

Objectives: The ankle kinematic characteristics of chronic ankle instability (CAI) at different gait phases and dimensions were not directly and overall explained. These characteristics have yet to be established. This study aimed to observe ankle kinematic changes of CAI, and explore their mechanisms, at different gait phases and dimensions in full gait cycle. Methods: A three-dimensional (3D) motion capture system measured the 3D ankle movements of 53 individuals with CAI (meanage = 25.11 ± 6.01years, meanheight = 170.77 ± 7.80 cm, meanmass = 64.28 ± 9.28 kg) and 53 healthy controls (meanage = 24.66 ± 6.32 years, meanheight = 169.98 ± 9.00 cm, meanmass = 63.11 ± 9.62 kg) during barefoot walking overground at a self-selected speed. Once the acquisition results were processed with visual 3D software, the kinematics data were exported, and the eight phases of the gait cycle were identified. Results: As compared with the control group, individuals with CAI displayed a significantly smaller plantarflexion in toe off (P = 0.049, Cohen's d = 0.387), a significantly increased inversion in heel strike (P = 0.007, Cohen's d = 0.271) and initial swing (P = 0.035, Cohen's d = 0.233), mid-swing (P = 0.019, Cohen's d = 0.232) and end-swing (P = 0.021, Cohen's d = 0.214), and significantly smaller eversion in mid stance（P = 0.010, Cohen's d = 0.288）and heel off (P = 0.033, Cohen's d = 0.089). Significant between-group differences in ankle kinematics were observed in the sagittal and frontal planes, but not in the horizontal plane, during walking. Conclusion: When walking, patients with CAI have altered sagittal- and frontal-plane kinematics during different stance and swing phases. These kinematic changes require multi-dimensional, dynamic, continuous functional assessment and specialized rehabilitation intervention.

Abstract Background Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown. Methods We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22. Results FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22-deficient mice. Conclusions FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis.

Abstract Metaproteomics can provide valuable insights into the functions of human gut microbiota (GM), but is challenging due to the extreme complexity and heterogeneity of GM. Data-independent acquisition (DIA) mass spectrometry (MS) has been an emerging quantitative technique in conventional proteomics, but is still at the early stage of development in the field of metaproteomics. Herein, we applied library-free DIA (directDIA)-based metaproteomics and compared the directDIA with other MS-based quantification techniques for metaproteomics on simulated microbial communities and feces samples spiked with bacteria with known ratios, demonstrating the superior performance of directDIA by a comprehensive consideration of proteome coverage in identification as well as accuracy and precision in quantification. We characterized human GM in two cohorts of clinical fecal samples of pancreatic cancer (PC) and mild cognitive impairment (MCI). About 70,000 microbial proteins were quantified in each cohort and annotated to profile the taxonomic and functional characteristics of GM in different diseases. Our work demonstrated the utility of directDIA in quantitative metaproteomics for investigating intestinal microbiota and its related disease pathogenesis.

The outcome of pancreatic adenocarcinoma (PAAD) patients is poor, given resistance to gemcitabine. Long noncoding RNA (lncRNA) has been implicated in the carcinogenesis of pancreatic cancer; however, its function and mechanism in PAAD resistance to gemcitabine (GEM) are yet unknown. Herein, we demonstrate that lncRNA DSCR9 is significantly reduced in PAAD in vitro and in vivo. CCK-8, BrdU and flow cytometry assays show that overexpression of DSCR9 markedly suppresses pancreatic cancer cell proliferation and invasion, and promotes apoptosis under gemcitabine treatment. BTG2 acts as a tumor suppressor by reducing the proliferation and invasion of pancreatic cancer cells and increasing gemcitabine-induced apoptosis. Immunofluorescence (IF) staining combined with fluorescence in situ hybridization (FISH) of pancreatic cancer tissues shows that DSCR9 and BTG2 are both increased in pancreatic cancer tissues. Luciferase assay shows that miR-21-5p simultaneously binds to DSCR9 and 3′UTR of BTG2; DSCR9 relieves miR-21-5p-induced inhibition of BTG2 by competing with BTG2 for miR-21-5p binding. Overexpression of miR-21-5p enhances the invasiveness of pancreatic cancer cells by promoting cancer cell proliferation and invasion and attenuating gemcitabine-induced apoptosis. Overexpression of miR-21-5p attenuates the effect of DSCR9 overexpression on BTG2 expression and invasiveness of pancreatic cancer cells. Finally, miR-21-5p expression is increased, while BTG2 expression is decreased in pancreatic cancer tissues. miR-21-5p is negatively correlated with DSCR9 and BTG2. In conclusion, the DSCR9/miR-21-5p/BTG2 axis modulates pancreatic cancer proliferation, invasion, and gemcitabine resistance.

Objiective: In presence of measurement uncertainty evaluation, the detection methods, with water-sodium chloride pretreatment, for health food was evaluated. Methods: A mathematical model was established to analysis of uncertainty sources. Then the individual components of uncertainty were evaluated. Finally, the combined uncertainty and extended uncertainty were calculated. Results: The uncertainty caused by several factors, including the fitting of the standard curve, the preparation of solution and standard, the repeatability of measurement, and the weigh of sample.The contents of mevastatin, lovastatin and simvastatin were 0.099 2, 0.101 0, 0.099 5 mg/kg in health foods, respectively. The relative combined standard uncertainties were about 0.003 2, 0.005 6, 0.005 1 mg/kg, k=2. Conclusion: Water-sodium chloride pretreatmen can reduce the interference of matrix and the uncertainty introduced by repeatability.

Heavy chromium pollution is a global sticky problem. In this study, an built-in proteomic and metabolomic method used to be used to look at the possible organic toxicity of Cr-contaminated answer based totally on an publicity scan with Penicillium janthinellum P1. The results showed that the high-Cr exposures resulted in cell injuries and signaling disturbances in P. janthinellum P1. Furthermore, Cr-contaminated answer triggered an amplify in glutamine and a sizable minimize in dimethylglycine, betaine and taurine, suggesting that the osmoregulatory metabolism of the P. janthinellum may additionally have been disturbed. The alteration of ATPase and mitochondrial associated proteins, combined with the upregulation of amino acids and carbohydrates, revealed that Cr contamination may disrupt the energy metabolism system. In addition, the secretory effects were confirmed by the upregulation of cytochrome P450 and deoxypodophyllotoxin, and the downregulation of penicillopepsin via proteomics. Therefore, dimethylglycine, glutamine, aspartate and cytochrome P450, all with remarkably alteration, were supposed to be selected as potential biomarkers of Cr contamination. This work assume to furnished new perception into the proteomic and metabolic toxicity of excessive Cr-contaminated area of interest in filamentous fungi, highlighted the mechanisms underlying toxicity and extended our knowledge of multi-omics jointly.

Abstract Background Metabolic syndrome (MetS) exacerbates susceptibility to inhalation exposures such as particulate air pollution, however, the mechanisms responsible remain unelucidated. Previously, we determined a MetS mouse model exhibited exacerbated pulmonary inflammation 24 h following AgNP exposure compared to a healthy mouse model. This enhanced response corresponded with reduction of distinct resolution mediators. We hypothesized silver nanoparticle (AgNP) exposure in MetS results in sustained pulmonary inflammation. Further, we hypothesized treatment with resolvin D1 (RvD1) will reduce exacerbations in AgNP-induced inflammation due to MetS. Results To evaluate these hypotheses, healthy and MetS mouse models were exposed to vehicle (control) or AgNPs and a day later, treated with resolvin D1 (RvD1) or vehicle (control) via oropharyngeal aspiration. Pulmonary lung toxicity was evaluated at 3-, 7-, 14-, and 21-days following AgNP exposure. MetS mice exposed to AgNPs and receiving vehicle treatment, demonstrated exacerbated pulmonary inflammatory responses compared to healthy mice. In the AgNP exposed mice receiving RvD1, pulmonary inflammatory response in MetS was reduced to levels comparable to healthy mice exposed to AgNPs. This included decreases in neutrophil influx and inflammatory cytokines, as well as elevated anti-inflammatory cytokines. Conclusions Inefficient resolution may contribute to enhancements in MetS susceptibility to AgNP exposure causing an increased pulmonary inflammatory response. Treatments utilizing specific resolution mediators may be beneficial to individuals suffering MetS following inhalation exposures.

Abstract PTENα and PTENβ (PTENα/β), two long translational variants of phosphatase and tensin homolog on chromosome 10 (PTEN), exert distinct roles from canonical PTEN, including promoting carcinogenesis and accelerating immune-resistant cancer progression. However, their roles in carcinogenesis remain greatly unknown. Herein, we report that, after secreting into the extracellular space, PTENα/β proteins are efficiently cleaved into a short N-terminal and a long C-terminal fragment by the proprotein convertase Furin at a polyarginine stretch in their N-terminal extensions. Although secreted PTENα/β and their cleaved fragment cannot enter cells, treatment of the purified C-terminal fragment but not cleavage-resistant mutants of PTENα exerts a tumor-suppressive role in vivo. As a result, overexpression of cleavage-resistant PTENα mutants manifest a tumor-promoting role more profound than that of wild-type PTENα. In line with these, the C-terminal fragment is significantly downregulated in liver cancer tissues compared to paired normal tissues, which is consistent with the downregulated expression of Furin. Collectively, we show that extracellular PTENα/β present opposite effects on carcinogenesis from intracellular PTENα/β, and propose that the tumor-suppressive C-terminal fragment of PTENα/β might be used as exogenous agent to treat cancer.

BackgroundAlgorithm malfunction may occur when there is a performance mismatch between the dataset with which it was developed and the dataset on which it was deployed.MethodsA baseline segmentation algorithm and a baseline classification algorithm were developed using public dataset of Lung Image Database Consortium to detect benign and malignant nodules, and two additional external datasets (i.e., HB and XZ) including 542 cases and 486 cases were involved for the independent validation of these two algorithms. To explore the impact of localized fine tuning on the individual segmentation and classification process, the baseline algorithms were fine tuned with CT scans of HB and XZ datasets, respectively, and the performance of the fine tuned algorithms was tested to compare with the baseline algorithms.ResultsThe proposed baseline algorithms of both segmentation and classification experienced a drop when directly deployed in external HB and XZ datasets. Comparing with the baseline validation results in nodule segmentation, the fine tuned segmentation algorithm obtained better performance in Dice coefficient, Intersection over Union, and Average Surface Distance in HB dataset (0.593 vs. 0.444; 0.450 vs. 0.348; 0.283 vs. 0.304) and XZ dataset (0.601 vs. 0.486; 0.482 vs. 0.378; 0.225 vs. 0.358). Similarly, comparing with the baseline validation results in benign and malignant nodule classification, the fine tuned classification algorithm had improved area under the receiver operating characteristic curve value, accuracy, and F1 score in HB dataset (0.851 vs. 0.812; 0.813 vs. 0.769; 0.852 vs. 0.822) and XZ dataset (0.724 vs. 0.668; 0.696 vs. 0.617; 0.737 vs. 0.668).ConclusionsThe external validation performance of localized fine tuned algorithms outperformed the baseline algorithms in both segmentation process and classification process, which showed that localized fine tuning may be an effective way to enable a baseline algorithm generalize to site-specific use.

Abstract Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34+ stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34+ stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells. These data challenged the dependency of OXPHOS for CML CD34+ cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.

Abstract Bcakground The dry root and rhizome of Salvia miltiorrhiza are used to treat cardiovascular diseases, chronic pain, and thoracic obstruction over 2000 years in Asian countries. For high quality, Sichuan Zhongjiang is regarded as the genuine producing area of S. miltiorrhiza. Given its abnormal pollen development, S. miltiorrhiza from Sichuan (S.m.-SC) relies on root reproduction and zymad accumulation; part of diseased plants present typical viral disease symptoms and seed quality degeneration. This study aim to detected unknown viruses from mosaic-diseased plants and establish a highly efficient virus-free regeneration system to recover germplasm properties. Results Tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were detected from mosaic-diseased plants. Primary apical meristem with two phyllo podium in 0.15–0.5 mm peeled from diseased plants were achieved 73.33% virus-free rate. The results showed that the medium containing MS, 0.5 mg/L 6-BA, 0.1 mg/L NAA, 0.1 mg/L GA3, 30 g/L sucrose and 7.5 g/L agar can achieve embryonic-tissue (apical meristem, petiole and leaf callus) high efficient organogenesis. For callus induction, the optimal condition was detected on the medium containing MS, 2 mg/L TDZ, 0.1 mg/L NAA by using secondary petiole of virus-free plants under 24 h dark/d condition for 21 d. The optimal system for root induction was the nutrient solution with 1/2 MS supplemented with 1 mg/L NAA. After transplant, the detection of agronomic metric and salvianolic acid B content confirmed the great germplasm properties of S.m.-SC virus-free plants. Conclusions A highly efficient virus-free regeneration system of S.m.-SC was established based on the detected viruses to recover superior seed quality. The proposed system laid support to control disease spread, recover good germplasm properties in S.m.-SC.

Abstract Background The overall response rate to checkpoint blockade remains unsatisfactory, partially due to the immune-suppressive tumor microenvironment. A retinoic acid-related orphan receptor γt (RORγt) agonist (LYC-55716) is currently used in clinical trials combined with anti-PD-1, but how the Th17 cell transcription factor RORγt enhances antitumor immunity of PD-1 in the tumor microenvironment remains elusive. Methods The expression of mRNA was analyzed using qPCR assays. Flow cytometry was used to sort and profile cells. Cell migration was analyzed using Transwell assays. Biacore was used to determine the binding affinity to the RORγt protein. The RORγt GAL4 cell-based reporter gene assay was used to measure activity in the RORγt driven luciferase reporter gene expression. Results We designed a potent and selective small-molecule RORγt agonist (8-074) that shows robust antitumor efficacy in syngeneic tumor models and improves the efficacy of anti‑PD‑1 in a murine lung cancer model. RORγt agonist treatment increased intratumoral CD8+ T cells, which were correlated with CXCL10 and monocyte-derived dendritic cells (MoDCs). In addition, the RORγt agonist promoted Type 17 T cell migration by upregulating CCL20 and CCR6 expression, and Type 17 T cell tumor infiltration. CCL20 induces MoDCs migration, and CXCL10 derived from MoDCs promotes CD8+ T cell migration. Conclusion Our results revealed that the RORγt agonist improved the efficacy of anti-PD-1. The RORγt agonist increased the migration of MoDCs, which increased the local levels of CXCL10, thus promoting CD8+ T cell tumor infiltration. Our findings provide the mechanistic insights implicating the RORγt agonist in immunotherapy and offer a strategy for targeting the RORγt agonist to improve PD-1 antibody efficacy in cancers.

Non-precious metal single-atom catalysts (NPM-SACs) with unique electronic structures and coordination environments have gained much attention in electrocatalysis owing to their low cost, high atomic utilization, and high performance. NPM-SACs on carbon support (NPM-SACs/CS) are promising because of the carbon substrate with a large surface area, excellent electrical conductivity, and high chemical stability. This review provides an overview of recent developments in NPM-SACs/CS for the electrocatalytic field. First, the state-of-the-art synthesis methods and advanced characterization techniques of NPM-SACs/CS are discussed in detail. Then, the structural adjustment strategy of NPM-SACs/CS for optimizing electrocatalytic performance is introduced concisely. Furthermore, we provide a comprehensive summary of recent advances in developing NPM-SACs/CS for important electrochemical reactions, including carbon dioxide reduction reaction, hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, and nitrogen reduction reaction. In the end, the existing challenges and future opportunities of NPM-SACs/CS in the electrocatalytic field are highlighted.

A grating-assisted hybrid plasmonic slot resonator is proposed and theoretically investigated as an on-chip surface-enhanced Raman scattering (SERS) sensor. A dielectric Bragg grating and a gold baffle are introduced into the hybrid plasmonic slot waveguide as two mirrors to form a plasmonic–dielectric cavity, in which the constructive interference of the input pump light greatly enhances the electric field. The grating reflects the wasted pump light for reverse secondary coupling and acts as a built-in notch filter for filtering out pump light from Raman scattered light simultaneously, improving the coupling efficiency and realizing a compact and miniaturized on-chip SERS sensor. Both the volumetric electric field enhancement and Raman collection efficiency are taken into account. The proposed scheme provides a simple, effective and universal method for improving the performance of the plasmonic-antennas-type waveguide-based SERS sensors.

Aims. This study explores the effects of curcumin as a therapeutic agent against oral squamous cell carcinoma (OSCC). Methods. We acquired the targets of curcumin from three digital databases, including the Comparative Toxicogenomics Database, Search Tool for Interactions of Chemicals, and SwissTargetPrediction. Then, we identified the differentially expressed genes (DEGs) and the weighted gene coexpression network analysis-based key modules using the expression profiles of GSE23558 to acquire the OSCC-related genes. Additionally, the GeneCards and Online Mendelian Inheritance in Man databases were also used to identify the OSCC-related genes. Finally, curcumin-OSCC interaction genes were obtained by overlapping curcumin targets and OSCC-related genes. The enrichment analysis was performed by the ClusterProfiler algorithm and Metascape, respectively. Then, a protein-protein interaction network was created, and the maximal clique centrality algorithm was used to identify the top 10 hub genes. Besides, we examined the expression levels of hub genes in OSCC using The Cancer Genome Atlas database. Results. 927 DEGs were identified, including 308 upregulated ones and 619 downregulated ones. The cluster one-step network construction function of the WGCNA algorithm recognized a soft-thresholding power of 6, and 9083 genes were acquired. 2591 OSCC-related genes were obtained by overlapping the GSE23558-identified genes and the OSCC-related genes from disease target bases. Finally, we identified 70 candidate drug-disease interaction genes by overlapping the disease-related genes with the curcumin target. The enrichment analysis suggested that response to oxidative stress, epithelial cell proliferation, and AGE/RAGE pathway might involve in the effect of curcumin on OSCC. The topologic study identified the ten hub genes, including VEGFA, AKT1, TNF, HIF1A, EGFR, JUN, STAT3, MMP9, EGF, and MAPK3. A significant difference was observed in VEGFA, AKT1, TNF, HIF1A, EGFR, MMP9, EGF, and MAPK3 expression levels between head and neck squamous cell carcinoma and the normal controls. However, no significant difference was observed in JUN (P=0.14) and STAT3 (P=0.054). Conclusion. This study provided an overview and basis for the potential mechanism of curcumin against OSCC. The following experiments should be performed to further understand the effectiveness and safety of curcumin in treating OSCC.

Abstract This study investigatedthe efficacy and safety offluticasone propionate nasal spray in treatment of adenoidal hypertrophic snoring in children.Fifty-six children with adenoidal hypertrophic snoring were enrolled. According to adenoidal-nasopharyngeal ratio (ANR) in lateral nasal X-ray examination,the children were assigned in moderategroup (23 cases) and severegroup (33 cases).The fluticasone propionate nasal spray was used for all patientsfor 4 weeks.In 56 patients, after treatment, compared with before treatment, the snoring, sleep apneaand nasal obstruction scores in moderategroupand the nasal obstruction score in severegroupwere significantly decreased,respectively (P < 0.05).The decreases of snoring, sleep apnea, mouth breathing and nasal obstruction scores after treatment in moderate group were significantly higher than those in severe group, respectively (P

BackgroundLeiomyosarcoma (LMS) is a malignant spindle-cell mesenchymal tumor originating from the smooth muscle cells, which mostly affects soft tissues and abdominopelvic organs over extremities. Primary LMS of the penis is a relatively uncommon mesenchymal tissue disease and a poorly understood condition.Case ReportA 69-year-old man presented with a growing, painless mass protruding from the penis. The irregularly lobulated lump was roughly 3 cm × 2.5 cm, with a smooth surface, tough texture, distinct boundary, and no tenderness. It was determined to be a penile tumor during the preoperative radiological evaluation. The patient underwent resection of the penile mass, followed by extended resection in the second operation. The diagnosis of LMS was verified by pathological examination. During a 20-month follow-up, the patient made a smooth recovery and remained disease-free.ConclusionAn immunohistochemical examination is essential for rendering this rare diagnosis. Radical excision of tumor lesions with negative cut margins is guaranteed to be the best treatment for primary penile LMS. Close follow-up should be provided due to the high rate of local recurrence.

Abstract Introduction A retrospective study was conducted to investigate the effectiveness and feasibility of fibroid enucleation in the anterior wall of the uterus by transverse uterine incision during cesarean section. Methods The medical history, surgical data, preoperative and postoperative changes in the blood system, and complications of 90 pregnant women who underwent myomectomy of the anterior uterine wall during cesarean section at the second Department of Maternal and Child Health Hospital of Fujian Province were analyzed retrospectively. Results No significant differences were noted in the leiomyoma number, pathological type, preoperative and postoperative hemoglobin level, perioperative bleeding incidence, blood transfusion frequency, postoperative fever incidence, and duration of lochia between the study and control groups. The proportion of large fibroids was slightly higher in the study group than in the control group (p

Abstract Introduction Postpartum hemorrhage is a serious complication of childbirth and is still the leading cause of maternal death worldwide. Lower uterine segment hemorrhage during cesarean section is an important cause of postpartum hemorrhage. Our objective is to expore the efficacy and safety of King’s combined uterine suture for hemostasis during cesarean section. Methods We examined 48 cases: 16 cases of pernicious placenta previa (including one case of twins), 11 cases of central placenta previa (including one case of twins), 18 cases of uterine scarring (including two cases of twins), as well as one case of twin pregnancy, two cases of breech presentation, and one case of pulmonary hypertension. The “King’s combined uterine suture” method for hemostasis was used in patients with lower uterine segment hemorrhage during cesarean section. Results The results showed that all patients had successful hemostasis during surgery, and there were no cases of hysterectomy. Conclusion We have concluded that King’s combined uterine suture is a fast and safe hemostasis method for cesarean section that can effectively reduce blood loss and restore the normal shape of the lower uterine segment. Furthermore, this suture method can reduce postpartum hemorrhage and hysterectomy rate, as well as improve maternal prognosis.

Abstract Protein acetylation has emerged to play pivotal roles in alcoholic liver disease (ALD). Sirutin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase involved in the regulation of aging, metabolism, and stress. However, the role of SIRT2 in ALD remains unclear. Here, we report that the SIRT2-mediated deacetylation–deubiquitination switch of CCAAT/enhancer-binding protein beta (C/EBPβ) prevents ALD. Our results showed that hepatic SIRT2 protein expression was negatively correlated with the severity of alcoholic liver injury in ALD patients. Liver-specific SIRT2 deficiency sensitized mice to ALD, whereas transgenic SIRT2 overexpression in hepatocytes significantly prevented ethanol-induced liver injury via normalization of hepatic steatosis, lipid peroxidation, and hepatocyte apoptosis. Mechanistically, we identified C/EBPβ as a critical substrate of SIRT2 implicated in ALD. SIRT2-mediated deacetylation at lysines 102 and 211 decreased C/EBPβ ubiquitination, resulting in enhanced protein stability and subsequently increased transcription of C/EBPβ-target gene LCN2. Importantly, hepatic deacetylated C/EBPβ and LCN2 compensation reversed SIRT2 deletion-induced ALD aggravation in mice. Furthermore, C/EBPβ protein expression was positively correlated with SIRT2 and LCN2 expression in the livers of ALD patients and was inversely correlated with ALD development. Therefore, activating SIRT2-C/EBPβ-LCN2 signaling pathway is a potential therapy for ALD.

Abstract Background Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited. Methods In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up. Results LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P

Rosiglitazone (Avandia) and pioglitazone (Actos) belong to the class of thiazolidinediones (TZDs) drugs that act by increasing insulin sensitivity and are widely used for treating diabetic patients with insulin resistance. TZDs exhibit anti-inflammatory and antioxidant properties, then may play an active role in inhibiting plaque formation and coronary atherosclerosis. But the results of evidence-based medicine suggest that TZDs may increase the risk of cardiovascular adverse events. To explore the dispute in depth, our meta-analysis aimed to evaluate the changes in vascular endothelial and plaque-related indicators following treatment with TZDs in diabetic patients with coronary atherosclerosis. According to our meta-analysis, TZDs showed an inhibiting effect on plaque progression and a protective effect on the vascular endothelium in patients with diabetes and coronary atherosclerosis. Interestingly, these effects may not depend on the regulation of inflammation and lipid metabolism. By this token, TZDs may develop a potential protective effect on myocardial infarction.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021231663].

This paper proposes an optimistic value iteration for steady-state mean–variance optimization in infinite-horizon discounted Markov decision processes (MDPs). The involved variance metric concerns reward variability in the long run, and future deviations are discounted to their present values. This mean–variance optimality criterion is time-inconsistent since its reward function depends on the mean, which renders traditional dynamic programming methods inapplicable. A family of policy/value iteration algorithms can be developed under a bilevel optimization algorithm framework, but there are still several problems to solve for a reinforcement learning (RL) extension. One problem is that in the value iteration, the inner optimization should achieve a near-optimal solution to ensure convergence before the outer update, which is required in every outer iteration. However, in an RL scenario, it is impractical to determine when the inner optimization should be stopped. To deal with this problem, we propose an optimistic value iteration, where the outer updates can be merged into the inner optimization with a learning rate. We prove the algorithm convergence and conduct a numerical experiment on portfolio management to validate the proposed algorithm.

BackgroundFusarium species are opportunistic causative agents of superficial and disseminated human infections. Fast and accurate identification and targeted antifungal therapy give help to improve the patients’ prognosis.ObjectivesThis study aimed to evaluate the effectiveness of matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) for Fusarium identification, and investigate the epidemiology and antifungal susceptibility profiles of clinical Fusarium isolates in Southern China.MethodsThere were 95 clinical Fusarium isolates identified by DNA sequencing of translation elongation factor 1-alpha (TEF1α) and MALDI-TOF MS, respectively. Antifungal susceptibility testing of isolates was performed by broth microdilution according to the CLSI approved standard M38-A3 document.ResultsSeven species complexes (SC) with 17 Fusarium species were identified. The most prevalent SC was the F. solani SC (70.5%, 67/95), followed by the F. fujikuroi SC (16.8%, 16/95). F. keratoplasticum within the F. solani SC was the most prevalent species (32.6%, 31/95). There were 91.6% (87/95) of isolates identified by MALDI-TOF MS at the SC level. In most of species, amphotericin B and voriconazole showed lower MICs compared to itraconazole and terbinafine. The F. solani SC showed higher MICs to these antifungal agents compared to the other SCs. There were 10.5% (10/95) of strains with high MICs for amphotericin B (≥8 μg/ml), terbinafine (≥32 μg/ml) and itraconazole (≥32 μg/ml) simultaneously, mostly focusing on F. keratoplasticum (9/10).ConclusionMALDI-TOF MS exhibited good performance on the identification of Fusarium strains at the SC level. The F. solani SC was the most prevalent clinical SC in Southern China. The MICs varied significantly among different species or SCs to different antifungal agents.

Abstract Background Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. Methods A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. Results WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. Conclusions The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.