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AIM: To compare the clinical effect of small incision lenticule extraction(SMILE)and implantable collamer lens(ICL)implantation on efficacy, safety and visual quality in patients with high myopia complicated with low astigmatism.METHODS: Retrospective study. A total of 80 cases(159 eyes)of high myopia and low astigmatism treated in the hospital from January 2021 to January 2022 were included, and they were divided into 46 cases(91 eyes)in SMILE group and 34 cases(68 eyes)in ICL implantation group by means of different surgical methods. The spherical equivalent, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), higher order aberrations of cornea and optical quality index, effectiveness and safety index were compared between the two groups before surgery and at 3 and 6 mo after surgery, and the surgical complications were counted.RESULTS: The spherical equivalent, UCVA and BCVA of both groups were all improved at 6 mo postoperatively(all P0.05). The root mean square values of total higher order aberration, spherical aberration, coma, vertical coma and horizontal coma in the SMILE group were higher than those in the ICL implantation group, and Strehl ratio(SR)in the ICL implantation group was higher than that in the SMILE group at 3 and 6 mo after surgery(all P

Abstract Objective The aim of this study is to evaluate the findings of existing systematic reviews (SRs) and provide scientific evidence on the efficacy and safety of whole-body vibration (WBV) in improving bone mineral density (BMD) in postmenopausal women, to provide recommendations and guidance for future high-quality clinical research and SRs. Methods We conducted searches in six databases (SinoMed, CNKI, Cochrane Library, Embase, PubMed, Web of Science) from the inception of the databases until July 31, 2023. The language was limited to Chinese or English. The methodological quality, risk of bias, and evidence grade of outcomes were evaluated using AMSTAR-2, ROBIS, and GRADE, respectively. Additionally, the degree of overlap in randomized controlled trials (RCTs) among the SRs was calculated using corrected covered area (CCA). Furthermore, we performed quantitative synthesis or descriptive analysis of the relevant data. All relevant operations were independently conducted by two individuals. Results A total of 15 SRs were included in the analysis, out of which three were qualitative descriptions and 12 were meta-analyses. According to AMSTAR-2, only two SRs were rated as low or moderate, while the remaining 13 SRs were rated as critically low quality. The ROBIS assessment indicated that seven SRs had a low risk of bias, while 8 SRs had a high risk of bias. The overall findings suggest that WBV does not have a significant advantage in improving BMD in postmenopausal women. Furthermore, the CCA results revealed a high overlap in RCTs across five outcomes among the 15 SRs. Only five SRs reported specific adverse reactions/events experienced by participants after WBV interventions, and none of the SRs reported any severe adverse events. Conclusion The existing evidence cannot establish definitive advantages of WBV in improving BMD in postmenopausal women. Therefore, we do not recommend the use of WBV for improving BMD in postmenopausal women. However, WBV may have potential value in maintaining BMD in postmenopausal women, further research is needed to confirm these findings.

Abstract Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-β secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.

Abstract This study aimed to develop a deep learning model to predict the risk stratification of all-cause death for older people with disability, providing guidance for long-term care plans. Based on the government-led long-term care insurance program in a pilot city of China from 2017 and followed up to 2021, the study included 42,353 disabled adults aged over 65, with 25,071 assigned to the training set and 17,282 to the validation set. The administrative data (including baseline characteristics, underlying medical conditions, and all-cause mortality) were collected to develop a deep learning model by least absolute shrinkage and selection operator. After a median follow-up time of 14 months, 17,565 (41.5%) deaths were recorded. Thirty predictors were identified and included in the final models for disability-related deaths. Physical disability (mobility, incontinence, feeding), adverse events (pressure ulcers and falls from bed), and cancer were related to poor prognosis. A total of 10,127, 25,140 and 7086 individuals were classified into low-, medium-, and high-risk groups, with actual risk probabilities of death of 9.5%, 45.8%, and 85.5%, respectively. This deep learning model could facilitate the prevention of risk factors and provide guidance for long-term care model planning based on risk stratification.

Ginsenoside Rd, one of the major components entering into the circulation from ginseng, is beneficial to health; however, its role and mechanism in improving T2DM require further exploration. In the current study, we explored the hypoglycemic effects of Rd in diabetic db/db mice and examined the underlying mechanisms. The results disclosed that after Rd treatment for four weeks, hyperglycemia, insulin resistance, and pyruvate intolerance were improved; moreover, hepatic steatosis was ameliorated. Additionally, Rd increased the phosphorylated Akt ratio in insulin-regulated peripheral tissues and decreased hepatic gluconeogenic gene expression. In vitro experimental results demonstrated that Rd decreased cellular glucose output from insulin-resistant mouse and human hepatocytes. Rd reduced gluconeogenic gene expression through inhibiting Foxo1 transcriptional activity. Taken together, our results suggest that Rd mitigates hyperglycemia in db/db mice by enhancing insulin sensitivity and diminishing hepatic gluconeogenesis, thus providing a theoretical principle for applying ginseng and ginsenoside Rd on curing T2DM.

Abstract Background Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. Methods This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. Results The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index

Abstract Background Toxoplasma gondii (T. gondii) is capable of infecting nearly all warm-blooded animals and approximately 30% of the global population. Though most infections are subclinical in immunocompetent individuals, congenital contraction can lead to severe consequences such as spontaneous abortion, stillbirth, and a range of cranio-cerebral and/or ocular abnormalities. Previous studies reported that T. gondii-infected pregnancy mice unveiled a deficit in both the amount and suppressive functions of regulatory T (Treg) cells, accompanied with reduced levels of forkhead box p3 (Foxp3). Recently, accumulative studies have demonstrated that microRNAs (miRNAs) are, to some extent, relevant to T. gondii infection. However, the link between alterations in miRNAs and downregulation of Foxp3 triggered by T. gondii has been only sporadically studied. Methods Quantitative reverse transcription polymerase chain reaction (RT-qPCR), protein blotting and immunofluorescence were employed to evaluate the impact of T. gondii infection and antigens on miRNA transcription and Foxp3 expression. Dual-luciferase reporter gene assays were performed to examine the fluorescence activity in EL4 cells, which were transfected with recombinant plasmids containing full-length/truncated/mutant microRNA-142a-3p (miR-142a) promoter sequence or wild type/mutant of Foxp3 3’ untranslated region (3’ UTR). Results We found a pronounced increase in miR-142a transcription, concurrent with a decrease in Foxp3 expression in T. gondii-infected mouse placental tissue. Similarly, comparable findings have been experimentally confirmed through the treatment of EL4 cells with T. gondii antigens (TgAg) in vitro. Simultaneously, miR-142a mimics attenuated Foxp3 expression, whereas its inhibitors markedly augmented Foxp3 expression. miR-142a promoter activity was elevated upon the stimulation of T. gondii antigens, which mitigated co-transfection of mutant miR-142a promoter lacking P53 target sites. miR-142a mimics deceased the fluorescence activity of Foxp3 3’ untranslated region (3’ UTR), but it did not affect the fluorescence activity upon the co-transfection of mutant Foxp3 3’ UTR lacking miR-142a target site. Conclusion In both in vivo and in vitro studies, a negative correlation was discovered between Foxp3 expression and miR-142a transcription. TgAg enhanced miR-142a promoter activity to facilitate miR-142a transcription through a P53-dependent mechanism. Furthermore, miR-142a directly targeted Foxp3 3’ UTR, resulting in the downregulation of Foxp3 expression. Therefore, harnessing miR-142a may be a possible therapeutic approach for adverse pregnancy caused by immune imbalances, particularly those induced by T. gondii infection.

Abstract Background Toxoplasma gondii, an obligate intracellular parasitic protozoa, infects approximately 30% of the global population. Contracting T. gondii at the primary infection of the mother can result in neonatal microcephaly, chorioretinitis, hydrocephalus, or mortality. Our previous study indicated that pregnant mice infected with T. gondii displayed a decrease in both the number and the suppressive ability of regulatory T cells, accompanied by the reduced Forkhead box P3 (Foxp3). Numerous studies have proved that microRNAs (miRNAs) are implicated in T. gondii infection, but there is meager evidence on the relationship between alterations of miRNAs and downregulation of Foxp3 induced by T. gondii. Methods Quantitative reverse transcription polymerase chain reaction was utilized to detect the transcriptions of miRNAs and Foxp3. Protein blotting and immunofluorescence were used to detect the expressions of Foxp3 and related transcription factors. The structure of mouse placenta was observed by hematoxylin and eosin (HE) staining. To examine the activity of miR-7b promoter and whether miR-7b-5p targets Sp1 to suppress Foxp3 expression, we constructed recombinant plasmids containing the full-length/truncated/mutant miR-7b promoter sequence or wildtype/mutant of Sp1 3' untranslated region (3' UTR) to detect the fluorescence activity in EL4 cells. Results In T. gondii-infected mice, miR-7b transcription was significantly elevated, while Foxp3 expression was decreased in the placenta. In vitro, miR-7b mimics downregulated Foxp3 expression, whereas its inhibitors significantly upregulated Foxp3 expression. miR-7b promoter activity was elevated upon the stimulation of T. gondii antigens, which was mitigated by co-transfection of mutant miR-7b promoter lacking peroxisome proliferator-activated receptor γ (PPARγ) target sites. Additionally, miR-7b mimics diminished Sp1 expression, while miR-7b inhibitors elevated its expression. miR-7b mimics deceased the fluorescence activity of Sp1 3' untranslated region (3' UTR), but it failed to impact the fluorescence activity upon the co-transfection of mutant Sp1 3' UTR lacking miR-7b target site. Conclusions T. gondii infection and antigens promote miR-7b transcription but inhibit Foxp3 protein and gene levels. T. gondii antigens promote miR-7b promoter activity by a PPARγ-dependent mechanism. miR-7b directly binds to Sp1 3' UTR to repress Sp1 expression. Understanding the regulatory functions by which T. gondii-induced miR-7b suppresses Foxp3 expression can provide new perspectives for the possible therapeutic avenue of T. gondii-induced adverse pregnancy outcomes. Graphical Abstract

AIM: To explore the clinical effect of small incision lenticule extraction(SMILE)on the treatment of myopic anisometropia.METHODS: Clinical data of 76 patients(146 eyes)with myopic anisometropia who received SMILE or femtosecond assisted laser in situ keratomileusis(FS-LASIK)in our hospital from January 2021 to December 2022 were retrospectively analyzed. The patients were divided into SMILE group(39 cases, 77 eyes)and FS-LASIK group(37 cases, 69 eyes)according to surgical methods. Uncorrected visual acuity(UCVA), diopter, anisometropia, corneal aberration and occurrence of postoperative complications were compared between the two groups at 1 wk, 1 and 3 mo after surgery.RESULTS: The UCVA of the two groups was improved after surgery compared with that before surgery, and the coma, trefoil, spherical aberration and total higher-order aberration were significantly increased compared to those before surgery(P

High blood sugar is the main feature of diabetes. In order to effectively regulate blood glucose levels, in this study, we used Gracilaria as raw material and found that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) were beneficial for decreasing fasting blood glucose, improving insulin resistance, enhancing the function of islet β-cells, and regulating the abnormal increase of TC, TG, LDL-c caused by hyperglycemia in diabetic mice. Moreover, 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) affected the gut microbiota structure of diabetic mice, decreased the Firmicutes/Bacteroidetes ratio, increased the abundance of Lactobacillus and Collinsella etc. and reduced the abundance of Helicobacter and Oscillibacter etc. In addition, the content of acetic acid and butyric acid in metabolites of short-chain fatty acids had increased, which had the effect of regulating blood glucose level. The results have showed that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) are potential marine foods for maintaining blood sugar health.

BackgroundDonepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy.MethodsWe retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age.ResultsOf the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment.ConclusionOur study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 μm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1–2.1 μm) and stage 3 (3.3–4.7 μm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder characterized by deficits in motor skills, with gross and fine motor dysfunction being the main symptom. This condition greatly impairs children’s daily life, learning, and social interaction. Symptoms typically appear during preschool or school age, and if left untreated, they can persist into adulthood. Thus, early assessment and intervention are crucial to improve the prognosis. This study aims to review the existing literature on DCD, providing a comprehensive overview of the assessment for children with DCD in terms of body functions and structures, activities and participation, and environmental factors within the framework of the International Classification of Functioning, Disability, and Health - Children and Youth (ICF-CY). Additionally, specific rehabilitation interventions will be described, offering valuable insights for the clinical assessment and intervention of children with DCD.

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have enabled breakthroughs in the clinical treatment of patients with HCC, but the overall response rate to ICIs in HCC patients is still low, and no validated biomarker is available to guide clinical decision making. Here, we demonstrated that the long non-coding RNA Lnc-CCNH-8 is highly expressed in HCC and correlates with poor prognosis. Functionally, elevated Lnc-CCNH-8 inactivated co-cultured T cells in vitro and compromised antitumor immunity in an immunocompetent mouse model. Mechanistically, up-regulated Lnc-CCNH-8 can sponge microRNA (miR)-217 to regulate the expression of PD-L1. In addition, Lnc-CCNH-8 can also stabilize PD-L1 through miR-3173/PKP3 axis. Furthermore, mice bearing tumors with high Lnc-CCNH-8 expression had significant therapeutic sensitivity to anti-PD-L1 monoclonal antibody treatment. More important, HCC patients with high levels of plasma exosomal Lnc-CCNH-8 had a better therapeutic response to ICIs. Taken together, our results reveal the function of Lnc-CCNH-8 in inducing immune escape from CD8+ T-cell-mediated killing by up-regulating PD-L1 in a miR-217/miR-3173-dependent manner, which also reveals a novel mechanism of PD-L1 regulation in HCC, and exosomal Lnc-CCNH-8 can serve as a predictive marker for immunotherapy response in HCC.

This research investigated the bond properties at high temperatures and with hybrid fiber addition between basalt fiber reinforced polymer (BFRP) bars and hybrid fiber-reinforced concrete (HFRC). The tensile strength and appearance morphology of BFRP bars were analyzed. Used scanning electron microscopy (SEM) to examine the microscopic morphology and used the bond-slip constitutive model to fit the bond-slip curves. When BFRP bars after exposed to 300 °C, their tensile strength dropped by 42%. With the increasing temperature, the bond strength and stiffness of normal concrete (NC) specimens decreased by 27.3 % and 67.5 %, respectively, while HFRC specimens decreased by 20.8 % and 55 %, respectively. Hybrid fibers increased the bond strength and stiffness of HFRC specimens by 27.1 % and 49.1 %, respectively. The best fitting models were the Malvar model and the Continuous Curve model.

ObjectiveThis study aimed to analyze the current state of research on preoperative anxiety in children through CiteSpace, VOSviewer, and the identification of hot spots and frontiers.MethodRelevant data were retrieved from the Web of Science Core Collection using the search terms children and preoperative anxiety. Data were analyzed using VOSviewer (version 1.6.18), CiteSpace (5.7. R5) software, and Scimago Graphica.ResultsA total of 622 articles were published between 2007 and 2022, with an increasing trend over time. Kain, Zeev N. (13; 2.09%) and Dalhousie University (15; 2.41%) were the most influential authors and most prolific institutions, respectively. The United States (121; 19.45%) was the country with the most publications. Pediatric anesthesia (55; 8.84%) had the most publications. High-frequency keywords were categorized into three themes, including nonpharmacologic interventions for preoperative anxiety in children, preoperative medications, and risk factors for anxiety; of these, “predictor” (38; 2016) and “sedative premedication” (20; 2016) were the most studied keywords over the past 6 years. “Distraction” (67; 2019) and “dexmedetomidine” (65; 2019) have been the main areas of interest in recent years.ConclusionResearch on preoperative anxiety in children has been the focus of increasing attention over the past fifteen years, with the majority of publications from high-income countries. This review provides a useful perspective for understanding research trends, hot topics, and research gaps in this expanding field.

Cuproptosis provides a new therapeutic strategy for cancer treatment and is thought to have broad clinical application prospects. Nevertheless, some oncological clinical trials have yet to demonstrate favorable outcomes, highlighting the need for further research into the molecular mechanisms underlying cuproptosis in tumors. Cuproptosis primarily hinges on the intracellular accumulation of copper, with lipid metabolism exerting a profound influence on its course. The interaction between copper metabolism and lipid metabolism is closely related to cuproptosis. Copper imbalance can affect mitochondrial respiration and lipid metabolism changes, while lipid accumulation can promote copper uptake and absorption, and inhibit cuproptosis induced by copper. Anomalies in lipid metabolism can disrupt copper homeostasis within cells, potentially triggering cuproptosis. The interaction between cuproptosis and lipid metabolism regulates the occurrence, development, metastasis, chemotherapy drug resistance, and tumor immunity of cancer. Cuproptosis is a promising new target for cancer treatment. However, the influence of lipid metabolism and other factors should be taken into consideration. This review provides a brief overview of the characteristics of the interaction between cuproptosis and lipid metabolism in cancer and analyses potential strategies of applying cuproptosis for cancer treatment.

Abstract The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is an emerging player in RNA modification landscape and responsible for the deposition of m6A in a few transcripts. AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development including hepatocellular carcinoma (HCC). Nevertheless, it remains unclear whether METTL16 mediated m6A modification of lncRNAs can regulate AURKA activation in cancer progression. Here we aimed to investigate the functional links between lncRNAs and the m6A modification in AURKA signaling and HCC progression. Here we show that LncRNA TIALD (transcript that induced AURKA Lysosomal degradation) was down-regulated in HCC tissues by METTL16 mediated m6A methylation to facilitate its RNA degradation, and correlates with poor prognosis. Functional assays reveal that TIALD inhibits HCC metastasis both in vitro and in vivo. Mechanistically, TIALD directly interacts with AURKA and facilitate its degradation through the lysosomal pathway to inhibited EMT and metastasis of HCC. AURKA’s specific inhibitor alisertib exerts effective therapeutic effect on liver cancer with low TIALD expression, which might provide a new insight into HCC therapy. Our study uncovers a negative functional loop of METTL16-TIALD-AURKA axis, and identifies a new mechanism for METTL16 mediated m6A-induced decay of TIALD on AURKA signaling in HCC progression, which may provide potential prognostic and therapeutic targets for HCC.

Abstract Background Migraine is a neurological disease characterized by moderate to severe headache and various neurological symptoms. It is often cause mood and anxiety disorders that can seriously affect quality of life. Acupuncture has been claimed to have a role in treating neuropsychiatric disorders and is becoming increasingly popular. However, it remains unclear whether current evidence is sufficient to support acupuncture in improving mental health in migraine patients. Objectives This systematic review and meta-analysis aimed to investigate the effect of acupuncture on the management of pain and mood disorders in patients with migraine. Methods We searched PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI) and Wan Fang Data Knowledge Service Platform for reports, conferences and academic papers published before January 1, 2022. Randomized controlled trials (RCTs) including acupuncture, sham acupuncture and medication for migraine were included. Stata 16.0 software and Cochrane RoB2.0 were used for data processing and migration risk analysis. Result Thirteen randomized controlled trials containing 1766 migraine patients were included in the present study, the results showed that compared with sham acupuncture and medication, acupuncture seemed to have advantage in improving SAS (WMD: -5.64;95% CI: -10.89, -0.39; p = 0.035) and SDS (WMD: -4.65; 95% CI: -9.25, -0.05; p = 0.048) in migraine patients. And it seems to be more effective in improving MH (SMD: 0.77; 95% CI: 0.19, 1.35; p = 0.009), VAS (SMD: -1.06; 95% CI: -1.73, -0.4; p = 0.002;) and MSQ (WMD: 4.76; 95% CI: 2.36, 7.15; p

Climate change significantly affects the quality characteristics of cereals. Climate factors such as accumulated temperature, daily temperature difference, rainfall and gas concentration and ratio affect the growing environment of cereals to varying degrees, leading to the changes of physiological and biochemical metabolic pathways of plants, and changes the traits of plants, which could have a series of effects on the quality of cereals. This paper summarized the research progress of different climatic factors affecting on the appearance quality, cooking quality, nutritional quality and eating quality of cereals. Many studies showed that climate factors had different effects on the color luster, particle size, grain integrity, water absorption, swelling rate, iodine blue value, solid content, microscopic changes of grain morphology, volatile components, protein, fat, starch and trace nutrients in grains. There are single and compound effects of various climatic factors on the quality of cereals, but the regulation mechanism of the compound interaction of various climatic factors still needs to be further studied.

Hot air drying is the key link of bulk grain and agricultural product processing. Because of the adjustment of national environmental protection and energy utilization policies in the new era, it is required to research and develop the energy saving technology of hot air drying for agricultural product. The current research is mostly limited to practical work tracking and empirical design, and there are also numerical calculations by heat and mass transfer theory. However these approaches have some limitations. Physical simulation is an effective potential method. In the process of studying the condensation increasing efficiency and energy saving technology, this paper has developed a test system which can simulate the actual hot air drying recycling energy. It has multi-parameter adjustable, graphical display drying state, energy consumption monitoring and other functions, and it can also provide effective means to study energy saving technology of hot air drying of agricultural product. The corn drying test for this system showed that energy recycling energy-saving drying could save energy 32%~56% when compared with ordinary open hot air drying.

Research on process parameter optimization and process intelligent control is an important element in the design and development of grain drying equipment. Existing methods mostly use simulation, device experiments or field experiments to obtain data, which have large differences with the actual drying results or the experimental process is time-consuming and vulnerable to interference. In this study, with reference to the process and structure of large continuous grain drying production equipment, a continuous grain drying simulation experimental system was developed and designed, including grain feeding equipment, dryer main body, grain discharge equipment, waste heat recovery, condensing device, hot air equipment and measurement and control system, which can simulate the grain drying operation process. This system can also optimize the drying process parameters, and carry out indoor grain drying quality change law, energy consumption law and production efficiency. The system can be used as the first-line staff post. The system could be used as the pre-service training for the workers on the production line, the experimental teaching of related majors in universities and colleges and the experimental research system of scientific research institutions.

Living convenience in public service facilities has attracted significant attention as a crucial indicator of urban development and quality improvement. However, the performance of plot patterns—a fundamental unit for precise control when measuring urban quality—influencing living convenience requires in-depth exploration. This study integrates multiple urban datasets with quantitative urban morphology methods to investigate the impact of various plot pattern features on living convenience. Specifically, we investigate the Inner Ring area of Shanghai as an empirical case. The assessment considers the diverse effects of facilities at different distances, accounting for the life radiuses of both older individuals and the general population. Additionally, the analysis of plot patterns includes planar and three-dimensional aspects, controlling key variables such as road network accessibility and centrality. The results indicate that, for small-scale plots, shape has a strong impact, while, for large-scale plots, the division and construction intensity within a block has a stronger influence. Furthermore, plots of different area types have different recommended construction intensities. Notably, for large-scale blocks, it is advisable to maintain a building density of around 0.3. In short, this study contributes to human-centered planning by providing targeted recommendations to address the existing deficiencies in plot morphology regulation and control from the perspective of quantitative urban morphology.

Low temperature is a limiting factor affecting plant growth and development. Casuarina equisetifolia, a typical tropical and subtropical tree important for the ecological restoration of coastal beaches, is sensitive to cold stress. By comparing cold tolerance between C. equisetifolia and Arabidopsis, we investigated the molecular basis underlying the cold sensitivity of C. equisetifolia. Transcriptomic analysis showed that the number of cold-induced genes in C. equisetifolia was significantly less than that in Arabidopsis, and notably, the response of cold-induced genes was also delayed in C. equisetifolia. Among the cold-induced genes, C-repeat binding factors (CBFs), the major transcription factors in cold acclimation in Arabidopsis, showed a delayed cold-induced expression in C. equisetifolia, despite that C. equisetifolia CBFs could restore the low temperature-sensitive phenotype of Arabidopsis cbfs triple mutants. Interestingly, some key cold-responsive genes (e.g., COR15A and COR15B) targeted by Arabidopsis CBF were absent in the C. equisetifolia genome and many cold-responsive genes in C. equisetifolia lacked the DRE element (i.e., CBF binding cis-element). Moreover, like in C. equisetifolia, many COR genes in other tropical/subtropical plants lacked the DRE element or were directly missing. These two factors could be the underlying reasons for the low-temperature sensitivity of C. equisetifolia and other tropical/subtropical plants.

The question of the use of fashionable words as markers that contribute to the identification of social characteristics of various subjects of speech is considered. The material for the study was the texts of microblogs of the Weibo Internet platform dedicated to China. We study the use of 10 fashion words of 2021, identified by the National Center for Monitoring and Research of Language Resources. Their functioning on the Weibo Internet site is analyzed. It has been established that the majority of Weibo users belong to the younger generation. The relevance of the study is due to the desire of Chinese society to build a strong welfare state, in which a significant role is given to young people. The novelty of the work lies in the fact that earlier the analysis of fashionable words of the Chinese language in the Internet discourse as a means of characterizing the younger generation was not carried out. It is shown that fashionable words on Weibo in most cases are used in positive contexts, which can be considered as “achieving a stable development of the country”, since all microblogs are dedicated to China. The author comes to the conclusion that the topics of blogs and the nature of the use of fashionable words in youth accounts testify to the confidence of Chinese youth in their future and the future of the country.

Abstract Background Insulin resistance precedes metabolic syndrome which increases the risk of type 2 diabetes and cardiovascular disease. However, there is a lack of safe and long-lasting methods for the prevention and treatment of insulin resistance. Gut microbiota dysbiosis can lead to insulin resistance and associated glucose and lipid metabolic dysfunction. Thus, the role of gut microbiota in metabolic diseases has garnered growing interest. Curcumin, the active ingredient of tropical plant Curcuma longa, has excellent prospects for the prevention and treatment of metabolic diseases. However, due to the extremely low bioavailability of curcumin, the mechanisms by which curcumin increases insulin sensitivity remains to be elucidated. This study aimed to elucidate the role of gut microbiota in mediating the effects of curcumin on improving insulin sensitivity in high-fat diet (HFD)-fed mice. Methods Glucose, insulin, and pyruvate tolerance were tested and hepatic triglycerides (TGs) content was measured in HFD-fed mice treated with curcumin (100 mg kg−1 d−1, p.o.) or vehicle for 4 weeks and aforementioned mice after gut microbiota depletion via antibiotic treatment for 4 weeks. Fecal microbiota transplantation (FMT) was conducted in endogenous gut microbiota-depleted HFD-fed mice. Glucose and lipid metabolic phenotypes were also measured in recipient mice colonized microbiota from vehicle- or curcumin-treated HFD-fed mice. The mechanisms underlying the effects of curcumin on increasing insulin sensitivity were testified by Western blotting, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Results Curcumin ameliorated HFD-induced glucose intolerance, insulin resistance, pyruvate intolerance, and hepatic TGs accumulation, while these effects were mediated by gut microbiota. Curcumin induced insulin-stimulated Akt phosphorylation levels in insulin-regulated peripheral tissues. The inhibitory effects of curcumin on the expressions of genes involved in hepatic gluconeogenesis and de novo lipogenesis were dependent on gut microbiota. Meanwhile, curcumin upregulated the expression of fibroblast growth factor 15 (FGF15) through gut microbiota. Conclusions The effects of curcumin on promoting insulin sensitivity were dependent on gut microbiota in HFD-fed mice. Moreover, curcumin at least partly exerted its effects on increasing insulin sensitivity via FGF15 upregulation. This study provided new ideas on nutritional manipulations of gut microbiota for the treatment of metabolic diseases.

Abstract As a highly infectious epidemic in aquaculture, Pseudomonas plecoglossicida infection results in high mortality of teleosts and serious economic losses. Host–pathogen interactions shape the outcome of an infection, yet we still understand little about the molecular mechanism of these pathogen-mediated processes. Here, a P. plecoglossicida strain (NZBD9) and Epinephelus coioides were investigated as a model system to characterize pathogen-induced host metabolic remodeling over the course of infection. We present a non-targeted metabolomics profiling of E. coioides spleens from uninfected E. coioides and those infected with wild-type and clpV-RNA interference (RNAi) strains. The most significant changes of E. coioides upon infection were associated with amino acids, lysophospatidylcholines, and unsaturated fatty acids, involving disturbances in host nutritional utilization and immune responses. Dihydrosphingosine and fatty acid 16:2 were screened as potential biomarkers for assessing P. plecoglossicida infection. The silencing of the P. plecoglossicida clpV gene significantly recovered the lipid metabolism of infected E. coioides. This comprehensive metabolomics study provides novel insights into how P. plecoglossicida shape host metabolism to support their survival and replication and highlights the potential of the virulence gene clpV in the treatment of P. plecoglossicida infection in aquaculture.

Abstract Polycomb repressive complex 1 (PRC1) is an essential epigenetic regulator that mainly controls histone H2A Lys119 mono‐ubiquitination (H2AK119ub). B cell‐specific Moloney murine leukemia virus Integration site 1 (BMI1) and really interesting new gene 1B (RING1B) are PRC1 core components and play critical roles in the development of various cancers. However, therapeutic agents targeting PRC1 are very limited. In this study, MS147, the first degrader of PRC1 core components, BMI1 and RING1B, is discovered via a novel protein complex degradation strategy that utilizes the target protein's interacting partner protein (embryonic ectoderm development (EED)). MS147, which comprises an EED small‐molecule binder linked to a ligand of the E3 ligase von Hippel‐Lindau (VHL), degrades BMI1/RING1B in an EED‐, VHL‐, ubiquitination‐, and time‐dependent manner. MS147 preferentially degrades BMI1/RING1B over polycomb repressive complex 2 (PRC2) core components. Consequently, MS147 effectively reduces H2AK119ub, but not histone H3 Lys27 tri‐methylation (H3K27me3), which is catalyzed by PRC2. Furthermore, MS147 effectively inhibits the proliferation of cancer cell lines that are insensitive to PRC2 inhibitors/degraders. Overall, this study provides a novel BMI1/RING1B degrader, which is a useful chemical tool to further investigate the roles of PRC1 in cancer, and a novel protein complex degradation strategy, which can potentially expand the degradable human proteome.

Toxoplasma gondii (T. gondii), a ubiquitous and obligatory intracellular protozoa, not only alters peripheral immune status, but crosses the blood-brain barrier to trigger brain parenchymal injury and central neuroinflammation to establish latent cerebral infection in humans and other vertebrates. Recent findings underscore the strong correlation between alterations in the peripheral and central immune environment and mood disorders. Th17 and Th1 cells are important pro-inflammatory cells that can drive the pathology of mood disorders by promoting neuroinflammation. As opposed to Th17 and Th1, regulatory T cells have inhibitory inflammatory and neuroprotective functions that can ameliorate mood disorders. T. gondii induces neuroinflammation, which can be mediated by CD4+ T cells (such as Tregs, Th17, Th1, and Th2). Though the pathophysiology and treatment of mood disorder have been currently studied, emerging evidence points to unique role of CD4+ T cells in mood disorder, especially those caused by T. gondii infection. In this review, we explore some recent studies that extend our understanding of the relationship between mood disorders and T. gondii.

Abstract Background To evaluate the safety and efficacy of bilateral balloon pulmonary angioplasty (BPA) as compared with unilateral BPA for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Method We reviewed 210 consecutive BPA sessions for 92 CTEPH patients, including 124 unilateral BPA sessions and 86 bilateral BPA sessions. Radiation exposure, operation details, lesions characteristics and the occurrence of complications were compared between unilateral BPA and bilateral BPA. 131 BPA sessions with a hemodynamics follow-up were included for efficacy analysis, in which hemodynamics changes were compared. Logistic regression analysis was used to identify factors associated with the occurrence of complications. Result Bilateral BPA treated more lobes, arteries and lesions [3 (2, 4) vs. 2 (1, 3) lobes, p

Organized malicious shilling attackers influence the output of the collaborative filtering recommendation systems by inserting fake users into the rating matrix within the database. The existence of shilling attack poses a serious risk to the stability of the system. To counter this specific security threat, many attack detection methods are proposed. Some of the past methods suffer from two disadvantages, the first being that they only analyze the rating matrix from a single perspective of user rating values and ignore other perspectives. Another is that some methods only use a single classifier to handle the classification of malicious attackers. Considering the above disadvantages, this paper proposes a gradient boosting method (named XGB-SAD) to achieve attack detection by combining double-view and gradient boosting. We first analyze the rating matrix with a double-view of time and item, which in turn defines the TPUS collection. Then our method uses eXtreme Gradient Boosting to perform heuristic iterative optimization of the model's objective function and uses the idea of ensemble learning to integrate multiple sets of base classifiers into strong classifier. The integrated strong classifiers are used to complete the detection of malicious attackers. Finally, we perform several experiments and the results demonstrate that XGB-SAD outperforms the comparison methods in terms of small-scale attack detection and overall detection, which proves the performance of our method.

Abstract Aqueous zinc metal batteries are noted for their cost-effectiveness, safety and environmental friendliness. However, the water-induced notorious issues such as continuous electrolyte decomposition and uneven Zn electrochemical deposition remarkably restrict the development of the long-life zinc metal batteries. In this study, zwitterionic sulfobetaine is introduced to copolymerize with acrylamide in zinc perchlorate (Zn(ClO4)2) solution. The designed gel framework with hydrophilic and charged groups can firmly anchor water molecules and construct ion migration channels to accelerate ion transport. The in situ generated hybrid interface, which is composed of the organic functionalized outer layer and inorganic Cl− containing inner layer, can synergically lower the mass transfer overpotential, reduce water-related side reactions and lead to uniform Zn deposition. Such a novel electrolyte configuration enables Zn//Zn cells with an ultra-long cycling life of over 3000 h and a low polarization potential (~ 0.03 V) and Zn//Cu cells with high Coulombic efficiency of 99.18% for 1000 cycles. Full cells matched with MnO2 cathodes delivered laudable cycling stability and impressive shelving ability. Besides, the flexible quasi-solid-state batteries which are equipped with the anti-vandalism ability (such as cutting, hammering and soaking) can successfully power the LED simultaneously. Such a safe, processable and durable hydrogel promises significant application potential for long-life flexible electronic devices.

Abstract Background Particular matter 2.5 (PM2.5) is one of the most important air pollutant, and it is positively associated with the development of chronic obstructive pulmonary disease (COPD). However, the precise underlying mechanisms through which PM2.5 promotes the development of COPD remains largely unknown. Methods Mouse alveolar destruction were determined by histological analysis of lung tissues and lung function test. Alveolar type II cells (AT2) to alveolar type I cells (AT1) transition in PM2.5-induced COPD mouse model was confirmed via immunofluorescence staining and qPCR analysis. The differentially expressed genes in PM2.5-induced COPD mouse model were identified by RNA-sequencing of alveolar epithelial organoids and generated by bioinformatics analysis. Results In this study, we found that 6 months exposure of PM2.5 induced a significantly decreased pulmonary compliance and resulted in pulmonary emphysema in mice. We showed that PM2.5 exposure significantly reduced the AT2 to AT1 cell transition in vitro and in vivo. In addition, we found a reduced expression of the intermediate AT2-AT1 cell process marker claudin 4 (CLDN4) at day 4 of differentiation in mouse alveolar organoids treated with PM2.5, suggesting that PM2.5 exposure inhibited AT2 cells from entering the transdifferentiation process. RNA-sequencing of mouse alveolar organoids showed that several key signaling pathways that involved in the AT2 to AT1 cell transition were significantly altered including the Wnt signaling, MAPK signaling and signaling pathways regulating pluripotency of stem cells following PM2.5 exposure. Conclusions In summary, these data demonstrate a critical role of AT2 to AT1 cell transition in PM2.5-induced COPD mouse model and reveal the signaling pathways that potentially regulate AT2 to AT1 cell transition during this process. Our findings therefore advance the current knowledge of PM2.5-induced COPD and may lead to a novel therapeutic strategy to treat this disease.

PurposePyroptosis exerts an undesirable impact on the clinical outcome of breast cancer. Since any single gene is insufficient to be an appropriate marker for pyroptosis, our aim is to develop a pyroptosis-related gene (PRG) signature to predict the survival status and immunological landscape for breast cancer patients.MethodsThe information of breast cancer patients was retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the gene expressions of this signature in breast cancer. Its prognostic value was evaluated by univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, receiver operating characteristics (ROCs), univariate/multivariate analysis, and nomogram. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore its potential biological function in breast cancer. The potential correlation between this signature and tumor immunity was revealed based on single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms.ResultsA PRG signature containing GSDMC, GZMB, IL18, and TP63 was created in a TCGA training cohort and validated in two validation GEO cohorts GSE58812 and GSE37751. Compared with a human mammary epithelial cell line MCF-10A, the expression levels of GSDMC, GZMB and IL18 were upregulated, while TP63 was found with lower expression level in breast cancer cells SK-BR-3, BT-549, MCF-7, and MDA-MB-231 using RT-qPCR assay. Based on univariate and multivariate Cox models, ROC curve, nomogram as well as calibration curve, it was revealed that this signature with high-risk score could independently predict poor clinical outcomes in breast cancer. Enrichment analyses demonstrated that the involved mechanism was tightly linked to immune-related processes. SsGSEA, ESTIMATE and CIBERSORT algorithms further pointed out that the established model might exert an impact on immune cell abundance, immune cell types and immune-checkpoint markers. Furthermore, individuals with breast cancer responded differently to these therapeutic agents based on this signature.ConclusionsOur data suggested that this PRG signature with high risk was tightly associated with impaired immune function, possibly resulting in an unfavorable outcome for breast cancer patients.

Rice (Oryza sativa L.) is a globally important food source providing carbohydrates, amino acids, and dietary fiber for humans and livestock. The branched-chain amino acid (BCAA) level is a complex trait related to the nutrient quality of rice. However, the genetic mechanism underlying the BCAA (valine, leucine, and isoleucine) accumulation in rice grains remains largely unclear. In this study, the grain BCAA contents and 239,055 SNPs of a diverse panel containing 422 rice accessions were adopted to perform a genome-wide association study (GWAS) using a recently proposed 3VmrMLM model. A total of 357 BCAA-content-associated main-effect quantitative trait nucleotides (QTNs) were identified from 15 datasets (12 BCAA content datasets and 3 BLUP datasets of BCAA). Furthermore, the allelic variation of two novel candidate genes, LOC_Os01g52530 and LOC_Os06g15420, responsible for the isoleucine (Ile) content alteration were identified. To reveal the genetic basis of the potential interactions between the gene and environmental factor, 53 QTN-by-environment interactions (QEIs) were detected using the 3VmrMLM model. The LOC_Os03g24460, LOC_Os01g55590, and LOC_Os12g31820 were considered as the candidate genes potentially contributing to the valine (Val), leucine (Leu), and isoleucine (Ile) accumulations, respectively. Additionally, 10 QTN-by-QTN interactions (QQIs) were detected using the 3VmrMLM model, which were putative gene-by-gene interactions related to the Leu and Ile contents. Taken together, these findings suggest that the implementation of the 3VmrMLM model in a GWAS may provide new insights into the deeper understanding of BCAA accumulation in rice grains. The identified QTNs/QEIs/QQIs serve as potential targets for the genetic improvement of rice with high BCAA levels.

It well known that vehicle detection is an important component of the field of object detection. However, the environment of vehicle detection is particularly sophisticated in practical processes. It is comparatively difficult to detect vehicles of various scales in traffic scene images, because the vehicles partially obscured by green belts, roadblocks or other vehicles, as well as influence of some low illumination weather. In this paper, we present a model based on Faster R–CNN with NAS optimization and feature enrichment to realize the effective detection of multi-scale vehicle targets in traffic scenes. First, we proposed a Retinex-based image adaptive correction algorithm (RIAC) to enhance the traffic images in the dataset to reduce the influence of shadow and illumination, and improve the image quality. Second, in order to improve the feature expression of the backbone network, we conducted Neural Architecture Search (NAS) on the backbone network used for feature extraction of Faster R–CNN to generate the optimal cross-layer connection to extract multi-layer features more effectively. Third, we used the object Feature Enrichment that combines the multi-layer feature information and the context information of the last layer after cross-layer connection to enrich the information of vehicle targets, and improve the robustness of the model for challenging targets such as small scale and severe occlusion. In the implementation of the model, K-means clustering algorithm was used to select the suitable anchor size for our dataset to improve the convergence speed of the model. Our model has been trained and tested on the UN-DETRAC dataset, and the obtained results indicate that our method has art-of-state detection performance.

Background: At present, a number of systematic reviews (SRs) on Xuebijing injection (a patent in China) in the treatment of acute pancreatitis (AP) or severe acute pancreatitis (SAP) have been published. However, the quality of evidence is uneven and has not been comprehensively evaluated.Aim: We evaluated the efficacy of Xuebijing injection for AP/SAP through an overview of SR, and to provide a scientific basis for its effectiveness and safety.Methods: We searched Cochrane Library, Embase, PubMed, SinoMed, CNKI, Wanfang, and VIP comprehensively. The retrieval period from inception to 30 November 2021, and the two reviewers independently complete the literature retrieval, data extraction and evaluation. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) were used to evaluate the methodological quality and reporting quality of the SRs, respectively. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the quality grading of outcomes and the risk of bias in SRs was evaluated by ROBIS Tool. Finally, the RCTs involved in SRs were synthesized. Stata15.1 was used for quantitative analysis of total effectiveness rate, time until relief of abdominal pain, time until relief of abdominal distension, and serum amylase level.Results: Nine eligible SRs were included, including 92 RCTs and 6,837 participants. The quality of SRs was relatively good, and the manuscript structures were relatively complete. However, the methodological quality of SRs was low or critically low. RoB rated 5 SRs as low risk of bias and 4 SRs as high risk of bias. In GRADE, a total of 47 results were included in the 9 SRs, of which 5 results (10.64%) were moderate quality, 22 results (46.81%) were low quality, and 20 results (42.55%) were very low quality. The results of data synthesis showed that Xuebijing injection combined treatment increased the total effectiveness rate of AP patients (RR = 1.19, 95% CI 1.17–1.23, p < 0.0001), and there was no heterogeneity between studies (I2 = 0.0%, p = 0.589). Compared with the control group, Xuebijing injection group shortened the abdominal pain and distension relief time in AP patients (WMD = −1.69, 95% CI −1.88–−1.50, p < 0.0001; WMD = −1.48, 95% CI −1.74–−1.23, p < 0.0001), with high heterogeneity (I2 = 84.3%, p = 0.000; I2 = 72.2%, p = 0.000). Serum amylase level was also reduced (WMD = −2.06, 95% CI −2.47–−1.64, p < 0.0001), with significant heterogeneity (I2 = 71.6%, p = 0.000). A total of one SR reported adverse drug reaction (ADR), no ADRs were observed in the control group.Conclusion: Although the quality of the evidence is not high, it can still reflect the clinical value of Xuebijing injection as an analgesic and anti-inflammatory traditional Chinese medicine in the treatment of AP/SAP. Therefore, future clinical studies should focus on the long-term efficacy and adverse reactions of drugs.Systematic Review Registration: (website), identifier (registration number).

Abstract Background Studies on the management of functional tricuspid regurgitation (TR) during mitral valve operations have drawn inconsistent conclusions. This study was designed to compare the treatment strategy of concomitant tricuspid annuloplasty (TAP) against isolated mitral valve replacement (MVR) in rheumatic mitral valve disease patients, and to assess the effect of concomitant TAP on postoperative right ventricular (RV) remodeling and function. Methods One hundred-seventy patients with rheumatic mitral valve disease receiving MVR were categorized into TAP group (n = 124) and non-TAP group (n = 46). Clinical and echocardiographic data were collected preoperatively and at 1-year follow-up. Three-dimensional echocardiographic indices of RV geometry and function were analyzed. Results At baseline, concomitant TAP group had larger RV end-diastolic volume, more decreased RV ejection fraction and RV longitudinal strain than non-TAP group (all P

BackgroundAs a serious public health problem, dementia has placed a heavy burden on society and families. Evidence suggests that the use of music therapy as a non-pharmacological intervention has certain advantages with respect to reducing the behavioral and psychological symptoms of dementia (BPSD) and improving the cognition and mental status of dementia patients. However, research trends and hotspots regarding music therapy intervention for dementia analysis have not been systematically studied via bibliometric analysis.MethodsWe searched the Web of Science Core Collection (WoSCC) for texts published between January 1, 2010, and October 31, 2021, and visualized country, institution, journal, keyword co-occurrence, keyword emergence and keyword clustering.ResultsA total of 217 articles from the WoSCC database were analyzed. In this research field, the annual number of publications has generally shown a slowly increasing trend, and the United States has the most publications and the most frequent cooperation among countries. University College London (UCL) has the most extensive influence among research institutions. Among articles, those published in the JOURNAL OF ALZHEIMER'S DISEASE were the most numerous, with 20 such articles being published, accounting for 9.22% (20/217) of the total. Comprehensive analysis of five clusters via biclustering shows that the research hotspots in this field during the past 11 years have mainly focused on the autobiographical memory, cognitive function, mental state and BPSD of dementia patients.ConclusionThis study conducted a bibliometric and visual analysis of relevant studies concerning music therapy intervention for dementia patients. Psychological problems faced by dementia patients and the topics of quality of life, individualized music therapy, the mental state of caregivers and other related topics may be important research directions in the future. Therefore, the question of how to develop standardized research protocols and identify unified efficacy evaluation indicators should be a focus of and difficulty for future research.

In recent years, inferring phylogenies has attracted lots of attention in both academic community and various application fields. Phylogenetic inference usually consists of a couple of evolutionary relationships, which can be represented as a phylogenetic tree. The phylogenetic reconstruction problem can be defined as an optimization problem, targeting at finding the most eligible tree among all possible topologies according to a selected criterion. Since the combinatorial number of possible topologies exceeds tolerance, various heuristic and metaheuristic methods have been proposed to find approximate solutions according to the selected criterion. However, different criterions are based on different principle and conflict with each other basically. In this line, scholars has proposed multi-objective evolutionary algorithm (MOEA) based on diverse criteria. Nevertheless, MOEA has suffered unbearable time consumption due to its inherent drawbacks of computational complexity and convergence. By studying the independence between the sub-populations in each time-consuming step of MOEA, the steps without global information can be designed to be executed in parallel, which can fundamentally address computational problems. Effective parallel algorithms designed with the characteristics of modern multicore clusters can solve such problems. In this sense, we propose a parallelized multi-objective evolutionary algorithm (MOEA-MC) by deploying on Spark, which added consensus into evolutionary algorithm to improve the quality of convergence and used membrane structure to keep equal solutions under different weights. In order to assess the performance achieved by the proposal, we have performed comparison among different methods on three real-world datasets separately. The results have certified that the solutions derived from MOEA-MC are superior to traditional methods in all studied datasets. And parallelized MOEA-MC can get dominant position and optimal Pareto-frontier simultaneously within minimal runtime.

Chronic constrictive pericarditis (CCP) is one of the common causes of cardiogenic cirrhosis; it is rare for a patient to have both CCP and recurrent black stool, so we consider that CCP causes cardiogenic cirrhosis. Cardiogenic cirrhosis caused portal hypertension which then resulted in gastrointestinal bleeding. Herein, we report a case of a 40-year-old Chinese woman suffering from CCP who had upper gastrointestinal bleed and had to undergo emergency surgery. Two years after the emergency surgery, multiple reexaminations showed significantly improved cardiac functions, hemoglobin, and WBC levels and gastrointestinal functions.

Background: Clinical evidence suggests that acupuncture is effective for relieving abdominal pain and distension in acute pancreatitis (AP). However, there is a lack of systematic reviews and meta-analyses that provide high-quality evidence of the efficacy and safety of acupuncture in this context.Aim: To assess the efficacy and safety of acupuncture for relieving abdominal pain and distension in AP.Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP, and China Biomedical Literature databases. Randomized controlled trials of acupuncture plus routine treatment (RT) vs. RT alone or RT plus sham/placebo acupuncture were included. Primary outcomes included total effectiveness rate, VAS scores for abdominal pain and distension, and time until relief of abdominal pain and distension. Secondary outcomes included time until recovery of bowel sound, time until first defecation, length of hospital stay, and APACHE II score.Results: Nineteen eligible original studies (n = 1,503) were included. The results showed that acupuncture in combination with RT had a significant advantage in terms of increasing the total effectiveness rate [risk ratio: 1.15; 95% confidence interval (CI): 1.06–1.24; P = 0.001]. Acupuncture also reduced the VAS score for abdominal pain [weighted mean difference (WMD): −1.45; 95% CI: −1.71 to −1.19; P < 0.0001] and the VAS score for abdominal distension (WMD: −0.71; 95% CI: −1.04 to −0.37; P < 0.0001) in patients with AP. Other results also showed the efficacy of acupuncture. One study reported adverse events after acupuncture.Conclusion: Acupuncture in combination with RT has a better effect than RT alone for relieving abdominal pain and distension in AP. More rigorous studies are needed to confirm this result.Systematic Review Registration: PROSPERO CRD42019147503 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=147503).

Background Spindle and kinetochore associated complex subunit 3 (SKA3) plays an important role in tumorigenesis and the progression of various tumors. But the relationship between SKA3 and early breast cancer remains unclear. The study aimed to explore the prognostic significance of SKA3 in breast cancer. Methods In the study, SKA3 expression was initially assessed using the Oncomine database and The Cancer Genome Atlas database (TCGA). Then, we presented validation results for RT-qPCR (quantitative reverse transcription PCR) and ELISA (enzyme-linked immunosorbent assay). The relationship between clinical characteristics and SKA3 expression was assessed by Chi-square test and Fisher’s exact test. Kaplan–Meier method and Cox regression analysis were conducted to evaluate the prognostic value of SKA3. Gene set enrichment analysis (GSEA) was performed to screen biological pathways using the TCGA dataset. Besides, single sample gene set enrichment analysis (ssGSEA) was utilized to identify immune infiltration cells about SKA3. Results SKA3 mRNA was expressed at high levels in breast cancer tissues compared with normal tissues. Chi-square test and Fisher’s exact test showed SKA3 expression was related to age, tumor (T) classification, node (N) classification, tumor-node-metastasis (TNM) stage, estrogen receptor (ER), progesterone receptor (PR), molecular subtype, and race. RT-qPCR results showed that SKA3 expression was overexpressed in ER, PR status, and molecular subtype in Chinese people. Kaplan–Meier curves implicated that high SKA3 expression was related to a poor prognosis in female early breast cancer patients. Cox regression models showed that high SKA3 expression could be used as an independent risk factor for female early breast cancer. Four signaling pathways were enriched in the high SKA3 expression group, including mTORC1 signaling pathway, MYC targets v1, mitotic spindle, estrogen response early. Besides, the SKA3 expression level was associate with infiltrating levels of activated CD4 T cells and eosinophils in breast cancer. Conclusion High SKA3 expression correlates with poor prognosis and immune infiltrates in breast cancer. SKA3 may become a biomarker for the prognosis of breast cancer.

Glioma is the most common primary intracranial tumor. Abnormal expression of CBX2 (ChromoBox2) is associated with tumorigenesis and tumor development. TCGA data in UALCAN showed that CBX2 was overexpressed in glioma tissue. To confirm the role of CBX2 in glioma, we regulated the level of CBX2 and conducted colony formation, Transwell, and CCK-8 assays to verify the effect of CBX2. The results showed that CBX2 knockdown reduced glioma cell proliferation and invasion and that the cells were less tumorigenic. CBX2 overexpression induced glioma cell proliferation and invasion and glioma stem cell self-renewal. The animal experiments showed that CBX2 knockdown inhibited glioma growth and improved survival time. CBX2 knockdown inhibited activation of the Akt/PI3K pathway. epidermal growth factor rescued the effects of CBX2. CBX2 could induce the growth and invasion of glioma cells via the Akt/PI3K pathway.

Mangostin, which has the function of anti-inflammatory, antioxidant, and anticancer, etc, is one of the main active ingredients of the hull of the mangosteen. The main objective of the study was to elucidate its anti-cancer function and possible mechanism. α-Mangostin was separated and structurally confirmed. MTT method was used to check the effect of mangostin on breast cancer cell proliferation. Then the effect of α-Mangostin on the transcriptional activity of RXRα was tested by dual-luciferase reporter gene assay. And Western blot (WB) was used to detect the expression of apoptosis-related proteins or cell cycle-associated proteins after treatment. Also, this study was to observe the effects of α-Mangostin on the invasion of breast cancer cell line MDA-MB-231. α-Mangostin regulates the downstream effectors of the PI3K/AKT signaling pathway by degrading RXRα/tRXRα. α-Mangostin can trigger PARP cleavage and induce apoptosis, which may be related to the induction of upregulated BAX expression and downregulation of BAD and cleaved caspase-3 expression in MDA-MB-231 cells through blockade of AKT signaling. The experiments verify that α-Mangostin have evident inhibition effects of invasion and metastasis of MDA-MB-231 cells. Cyclin D1 was involved in the anticancer effects of α-Mangostin on the cell cycle in MDA-MB-231 cells. α-Mangostin induces apoptosis, suppresses the migration and invasion of breast cancer cells through the PI3K/AKT signaling pathway by targeting RXRα, and cyclin D1 has involved in this process.

During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.

C18H20ON4F12P2, triclinic, P1̄ (no. 2), a = 9.393(8) Å, b = 10.894(10) Å, c = 13.716(12) Å, α = 107.741(14)°, β = 100.379(15)°, γ = 92.869(14)°, V = 1306.7(19) Å3, Z = 2, Rgt(F) = 0.0916, wRref(F2) = 0.1970, T = 296(2) K.

Herein we report a novel palladium-catalyzed reaction that results in phenanthrene derivatives using aryl iodides, ortho-bromobenzoyl chlorides and norbornadiene in one pot. This dramatic transformation undergoes ortho-C–H activation, decarbonylation and subsequent a retro-Diels–Alder process. Pleasantly, this protocol has a wider substrate range, shorter reaction times and higher yields of products than previously reported methods.

Coconut is a tropical fruit whose flesh has high flavor quality and nutritional value; however, the differences between coconut varieties are still unclear. Here, volatiles and non-volatiles were profiled at three ripening stages by HS-SPME/GC-MS and UHPLC-MS/MS in two coconut varieties (Hainan Tall, HT and Green Dwarf, GD). Four metabolite classes of volatiles were associated with good aroma including hydrocarbons, benzenoids, alcohols and esters, and these volatiles were generally higher in GD, especially at 7 and 9 months of coconut growth. Pathway-based metabolomics revealed that flavonols and their derivatives were significantly enriched in HT, and some of these metabolites were key determinants of HT flesh bitterness, including kaempferol 7-O-glucoside, a known bitter metabolite. Despite the overall accumulation of amino acids, including L-alanine, L-serine and L-methionine in GD, comparative metabolomics revealed that HT flesh provides a higher content of vitamins than GD. This study sheds light on the metabolic pathways and key metabolites differentiating the flesh flavor quality and nutritional value among coconut varieties, and reveals the possible mechanisms of flavor formation and regulation in coconut fruits.