Search

Realizing efficient immobilization of lithium polysulfides (LiPSs) as well as reversible catalytic conversion between LiPSs and the insoluble Li2S is vital to restrain the shuttle effect, which requires highly reactive catalysts for high-performance Li-S batteries. Here, three-dimensional ordered porous Mo-based metal phosphides (3DOP Mo3P/Mo) with heterogeneous structures were fabricated and utilized as separator-modified coatings for Li-S batteries to catalyze the conversion of LiPSs. The adsorption, catalytic and electrochemical performance of the corresponding cells were compared among 3DOP Mo3P/Mo and 3DOP Mo, by kinetic and electrochemical performance measurements. It was found that the cell with 3DOP Mo3P/Mo modified separator deliver better electrochemical performance, with a high specific capacity of 469.66 mAh g−1 after 500 cycles at a high current density of 1°C. This work provides an idea and a guideline for the design of the separator modification for high-performance Li-S batteries.

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

General anesthesia can impact a patient’s memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.

Rock types with similar lithological components and pore structures form the basic units of porous limestone reservoirs; this influences the reservoir evaluation efficiency and water injection development. As the main oil and gas pay zone in central Iraq, the Cretaceous Khasib Formation reservoirs are influenced by deposition, dissolution, and cementation. There is strong vertical heterogeneity in the most important zone of the Kh2 layer, with diverse rock types and complex pore structures. Based on core observation and casting thin-section identification, the Kh2 layer in the study area was divided into eight lithofacies types as argillaceous bioclastic wackestone, planktic foraminiferium wackestone, lamellar bioclastic wackestone, intraclastic–bioclastic packstone, patchy green algae packstone, green algae and pelletoid packstone, benthic foraminiferium–bioclastic packstone, and intraclastic grainstone. Along with the reservoir void space types of the lithofacies, capillary pressure curves are used to quantitatively analyze the throat and pore features of the different lithofacies. From the porosity–permeability cross-plot characteristics and distribution of pore types, 14 petrophysical facies are obtained. Finally, based on the differences between the lithofacies and petrophysical facies, the Kh2 member is divided into 13 rock types with different geological origins and petrophysical characteristics. Among these, the rock type RT1-8-14 has the best and rock type RT1-1-1 has the worst physical properties among the reservoir rock types. This study provides an optimization method for carbonate reservoir evaluation and is expected to be beneficial for efficient development of similar carbonate reservoirs.

ObjectivesTo assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.MethodsSystematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria.ResultsA total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P

BackgroundThe safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious.AimsThis study evaluates DAPT’s effectiveness and safety for these patients.MethodsThis review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4.ResultsAnalysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46–0.59, p

It has been widely accepted that China is one of the biggest natural gas consumers. Related to the imports of LNG, China stands in a very uncomfortable situation. Most domestic gas reservoirs fall within deep water drive gas reservoirs inordinately, which has entered the production depletion stage. Accurate estimation of SEC recoverable reserves of deep water drive gas reservoirs is of great significance for gas consumption planning and peak shaving. The existing calculation methods of recoverable reserves mainly consist of static methods and dynamic methods. In the early stage of exploration and development, the volumetric method has often been utilized to calculate the recoverable reserves. With the continuous development of gas reservoirs, the main methods for evaluation are dynamic methods, including the successive subtraction of production method, water drive curve method, prediction model method, attenuation curve method, improved virtual curve method, and material balance method for deep gas reservoirs.

PurposeThis research investigated the impact of the COVID-19 pandemic on the mental well-being and sleep quality of students in higher vocational colleges in Sichuan, China, identifying key factors influencing their psychological health during this period.MethodsBetween January and February 2022, a comprehensive survey was conducted among students from several higher vocational colleges in Sichuan, utilizing a randomized selection approach to involve 3,300 participants. Data were collected through direct interviews executed by skilled interviewers.ResultsOut of 3,049 valid responses, a significant number reported experiencing symptoms of poor mental health, anxiety, depression, and insomnia, with prevalence rates of 21.2%, 9.7%, 14.1%, and 81.9%, respectively. Factors contributing positively to mental health and sleep included a higher family economic status, reduced stress from the pandemic, and decreased online activity. Conversely, lack of physical activity post-pandemic, disruptions to education and employment, and deteriorating relationships emerged as negative influencers. Interestingly, a lack of pre-pandemic mental health knowledge acted as a protective factor against insomnia.ConclusionThe ongoing management of COVID-19 has notably influenced the psychological and sleep health of vocational college students, driven by economic, emotional, lifestyle, and educational factors. The findings underscore the necessity for targeted interventions to address these challenges effectively.

Some Brucella spp. are important pathogens. According to the latest prokaryotic taxonomy, the Brucella genus consists of facultative intracellular parasitic Brucella species and extracellular opportunistic or environmental Brucella species. Intracellular Brucella species include classical and nonclassical types, with different species generally exhibiting host preferences. Some classical intracellular Brucella species can cause zoonotic brucellosis, including B. melitensis, B. abortus, B. suis, and B. canis. Extracellular Brucella species comprise opportunistic or environmental species which belonged formerly to the genus Ochrobactrum and thus nowadays renamed as for example Brucella intermedia or Brucella anthropi, which are the most frequent opportunistic human pathogens within the recently expanded genus Brucella. The cause of the diverse phenotypic characteristics of different Brucella species is still unclear. To further investigate the genetic evolutionary characteristics of the Brucella genus and elucidate the relationship between its genomic composition and prediction of phenotypic traits, we collected the genomic data of Brucella from the NCBI Genome database and conducted a comparative genomics study. We found that classical and nonclassical intracellular Brucella species and extracellular Brucella species exhibited differences in phylogenetic relationships, horizontal gene transfer and distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes, showing the close relationship between the genetic variations and prediction of phenotypic traits of different Brucella species. Furthermore, we found significant differences in horizontal gene transfer and the distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes between the two chromosomes of Brucella, indicating that the two chromosomes had distinct dynamics and plasticity and played different roles in the survival and evolution of Brucella. These findings provide new directions for exploring the genetic evolutionary characteristics of the Brucella genus and could offer new clues to elucidate the factors influencing the phenotypic diversity of the Brucella genus.

ObjectiveInflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke.MethodsPatients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C 1.1, which indicated a positive remodeling.ResultsOut of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13–3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08–6.77, P = 0.034).ConclusionsIn patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

TetR-family transcriptional regulators are widely distributed among bacteria and involved in various cellular processes such as multidrug and inhibitor resistance. Zymomonas mobilis is a industrial bacterium for lignocellulosic ethanol production. Although TetR-family regulators and their associated RND-family efflux pumps in Z. mobilis have been identified to be differentially expressed under various inhibitors and stressful conditions, there are no systematic investigation yet. In this study, bioinformatic analyses indicated that there are three TetR-family transcriptional regulators (ZMO0281, ZMO0963, ZMO1547) and two RND-family efflux pumps (ZMO0282-0285, ZMO0964-0966) adjacent to corresponding TetR-family regulators of ZMO0281 and ZMO0963 in Z. mobilis. Genetics studies were then carried out with various mutants of TetR-family regulators constructed, and ZMO0281 was characterized to be related to acetate tolerance. Combining transcriptomics and dual-reporter gene system, this study demonstrated that three TetR-family regulators repressed their adjacent genes specifically. Moreover, TetR-family regulator ZMO0281 might also be involved in other cellular processes in the presence of acetate. In addition, the upregulation of RND-family efflux pumps due to ZMO0281 deletion might lead to an energy imbalance and decreased cell growth in Z. mobilis under acetate stress. The systematic investigation of all three TetR-family regulators and their roles on a major lignocellulosic inhibitor acetate tolerance in Z. mobilis thus not only unravels the molecular mechanisms of TetR-family regulators and their potential cross-talks on regulating RND-family efflux pumps and other genes in Z. mobilis, but also provides guidance on understanding the roles of multiple regulators of same family in Z. mobilis and other microorganisms for efficient lignocellulosic biochemical production.

BackgroundSince abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.MethodsArticles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.ResultsOver the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.ConclusionThe study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.

IntroductionThe role of systolic blood pressure (SBP) variability in the pathogenesis of cerebral amyloid angiopathy (CAA) as an underlying cause of intracerebral hemorrhage (ICH) is unknown. We studied SBP variability before ICH according to CAA severity at autopsy.MethodsWe collected office (primary care or hospital clinic) BP readings during 10 years before first-ever ICH onset in adults who died and had brain research autopsy in the Lothian IntraCerebral Hemorrhage, Pathology, Imaging, and Neurological Outcome (LINCHPIN), prospective, population-based, inception cohort study. A neuropathologist assessed CAA severity using a histopathological rating scale, masked to BP readings. Functional principal component analysis was used to model SBP levels by time before ICH, and logistic regression models assessed associations of SBP variability indices with CAA severity (moderate-severe vs. absent-mild) adjusted for age, gender, and mean SBP.ResultsAmong 72 adults (median age 81 [interquartile range 76–86], 56% female, median number of SBP readings 11 [3–19]), patients with moderate-severe CAA had similar mean SBP (143 vs. 145 mmHg, P = 0.588) but lower SBP variability (SBP standard deviation [SD] 14 vs. 17 mmHg, P = 0.033) compared with patients with absent-mild CAA, and their SBP trajectories seemed to differ over 10 years before ICH. The odds of moderate-severe CAA were higher with lower maximum SBP (adjusted OR per 10 mmHg lower: 1.53, 95% confidence interval [CI] 1.09–2.15; P = 0.015) and lower SBP range (1.29 [1.03–1.61]; P = 0.028), but not SBP SD (1.95 [0.87–4.38]; P = 0.11).DiscussionCompared with absent-mild autopsy-verified CAA, moderate-severe CAA is associated with lower maximum and range of pre-morbid SBP.

BackgroundImmune agents targeting Programmed cell death-1 (PD-1) are a new type of cancer treatment drugs. By inhibiting the interaction between PD-1 and PD-L1, the ability of the immune system to attack tumor cells is enhanced. These immune preparations have shown significant efficacy in the treatment of various malignant tumors. However, like other drugs, immune preparations targeting PD-1 may also cause side effects, including arthralgia. Therefore, we conduct a meta-analysis to assess whether immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients will lead to arthralgia adverse events.MethodsWe conducted a comprehensive search across multiple databases, including PubMed, Medline (Ovid), Web of Science, Cochrane, Embase, Scopus, CKNI, Wang fang, VIP database, Sino Med, and Clinical Trails, to identify relevant studies. The search encompassed articles published up until June 20th, 2023. The primary outcome is adverse events about arthralgia and secondary outcomes are any other related with arthralgia. Data extraction was carried out by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was employed to assess the included studies. The systematic review and meta-analysis were conducted using RevMan 5.3 software.Results12 studies are included in the meta-analysis. All included studies were determined to have a low risk of random sequence generation bias. The meta-analysis result showed that arthralgia RR = 1.11, 95% CI [0.88, 1.40], I2 = 56%, back pain RR = 1.86, 95% CI [1.07, 3.26], I2 = 84%, myalgia RR = 0.49, 95% CI [0.27, 0.88], I2 = 86% and muscular pain RR = 1.97, 95% CI [1.40, 2.77], I2 = 23%.ConclusionThe use of targeted inhibitors may lead to an increased incidence of back pain, while potentially reducing the occurrence of myalgia. On the other hand, immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients may not cause arthralgia and muscular pain.

Multi-scroll attractors have attracted attention because of their more complex topological structures and artificially controllable attractor structures. This paper proposes a new nonvolatile magnetic-controlled memristor and uses it to simulate the effect of membrane flux changes caused by neuronal exposure to electromagnetic radiation. A series of complex chaotic phenomena are found by plotting phase diagrams, bifurcation diagrams, attractor domains and 01 tests, including multi-scroll chaotic attractors controlled by memristors, symmetric bifurcation behavior, coexistence phenomena enhanced by initial offset. The mechanisms behind them are explained through equilibrium point analysis. A dual memristive HNN (MHNN) coupling synchronization model is proposed to simulate the synchronization between regions within the human brain. The Lyapunov function of the error is constructed to prove that this coupling synchronization scheme is ultimately bounded. The feasibility of this synchronization scheme is verified by establishing a Simulink model and conducting simulation experiments.

Waterfowl, such as ducks, are natural hosts for avian influenza viruses (AIVs) and act as a bridge for transmitting the virus to humans or susceptible chickens. Since 2013, chickens and ducks have been threatened by waterfowl-origin H5N6 subtype AIVs in China. Therefore, it is necessary to investigate the genetic evolution, transmission, and pathogenicity of these viruses. In this study, we determined the genetic characteristics, transmission, and pathogenicity of waterfowl-origin H5N6 viruses in southern China. The hemagglutinin (HA) genes of H5N6 viruses were classified into the MIX-like branch of clade 2.3.4.4h. The neuraminidase (NA) genes belonged to the Eurasian lineage. The PB1 genes were classified into MIX-like and VN 2014-like branches. The remaining five genes were clustered into the MIX-like branch. Therefore, these viruses belonged to different genotypes. The cleavage site of the HA proteins of these viruses was RERRRKR/G, a molecular characteristic of the H5 highly pathogenic AIV. The NA stalk of all H5N6 viruses contained 11 amino acid deletions at residues 58–68. All viruses contained 627E and 701D in the PB2 proteins, which were molecular characteristics of typical bird AIVs. Furthermore, this study showed that Q135 and S23 viruses could replicate systematically in chickens and ducks. They did not cause death in ducks but induced mild clinical signs in them. All the infected chickens showed severe clinical signs and died. These viruses were shed from the digestive and respiratory tracts and transmitted horizontally in chickens and ducks. Our results provide valuable information for preventing H5N6 avian influenza outbreaks.

BackgroundThe coexistence of Crohn's disease (CD) and acute appendicitis (AA) is rare. In this situation, therapeutic experience is lacking and the strategy is paradoxical and intractable. Appendectomy is the gold standard for the treatment of AA whereas a nonsurgical approach is recommended for CD.Case summaryA 17-year-old boy was hospitalized for right lower abdominal pain with fever of 3 days. He had the CD for 8 years. Two years ago, he underwent surgery for anal fistula with the complication of CD. His temperature was elevated at 38.3°C at admission. On physical examination, there was McBurney tenderness with mild rebound tenderness. Abdominal ultrasonography showed that the appendix was notably enlarged and dilated at 6.34 cm long and 2.76 cm wide. These findings were suggestive of uncomplicated AA in this patient with active CD. Endoscopic retrograde appendicitis therapy (ERAT) was performed. The patient had complete pain relief immediately after the procedure without tenderness in the right lower abdomen. During 18 mo follow-up, he had no more attacks in his right lower abdomen.ConclusionERAT was effective and safe in a CD patient with coexisting AA. Such cases can avoid surgery and its-related complications.

The vulnerability of the oral cavity to SARS-CoV-2 infection is well-known, and cancer patients are at a higher risk of COVID-19, emphasizing the need to prioritize this patient population. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers associated with early metastasis and poor prognosis. It has been established that cancerous tissues express Cathepsin L (CTSL), a proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is essential to evaluate the correlation between disease outcomes and CTSL expression in cancer tissues and predict the susceptibility of cancer patients to SARS-CoV-2. In this study, we used transcriptomic and genomic data to profile CTSL expression in HNSCC and developed a CTSL signature that could reflect the response of HNSCC patients to chemotherapy and immunotherapy. Additionally, we investigated the relationship between CTSL expression and immune cell infiltration and established CTSL as a potential carcinogenic factor for HNSCC patients. These findings could aid in understanding the mechanisms underlying the increased susceptibility of HNSCC patients to SARS-CoV-2 and contribute to the development of therapy for both HNSCC and COVID-19.

Background: Gene editing tools using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related systems have revolutionized our understanding of cancer. The purpose of this study was to determine the distribution, collaboration, and direction of cancer research using CRISPR.Methods: Data from the Web of Science (WoS) Core Collection database were collected from 4,408 cancer publications related to CRISPR from 1 January 2013to 31 December 2022. The obtained data were analyzed using VOSviewer software for citation, co-citation, co-authorship, and co-occurrence analysis.Results: The number of annual publications has grown steadily over the past decade worldwide. The United States was shown, by far, to be the leading source of cancer publications, citations, and collaborations involving CRISPR than any other country, followed by China. Li Wei (Jilin University, China), and Harvard Medical School (Boston, MA, United States) were the author and institution with the most publications and active collaborations, respectively. The journal with the most contributions was Nature Communications (n = 147) and the journal with the most citations was Nature (n = 12,111). The research direction of oncogenic molecules, mechanisms, and cancer-related gene editing was indicated based on keyword analysis.Conclusion: The current study has provided a comprehensive overview of cancer research highlights and future trends of CRISPR, combined with a review of CRISPR applications in cancer to summarize and predict research directions and provide guidance to researchers.

ObjectiveThis study aimed to access hepatitis B virus (HBV) reactivation and its effect on survival in HBV-related hepatocarcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs).MethodsIn this single-center retrospective study, we enrolled 119 HBV-related unresectable advanced HCC patients receiving TACE combined with TKIs plus ICIs. Risk factors for HBV reactivation were analyzed by logistic regression. Kaplan-Meier method was applied to draw the survival curve, and log-rank test was used to compare survival between patients with and without HBV reactivation.ResultsA total of 12 patients (10.1%) encountered HBV reactivation in our study, of which only 4 patients received antiviral prophylaxis. The incidence of HBV reactivation was 1.8% (1/57) in patients with detectable baseline HBV DNA and 4.2% (4/95) in patients with antiviral prophylaxis respectively. Lack of prophylactic antiviral treatment (OR=0.047, 95%CI 0.008-0.273, P=0.001) and undetectable HBV DNA (OR=0.073, 95%CI 0.007-0.727, P=0.026) were independent risk factors for HBV reactivation. The median survival time (MST) for all patients was 22.4 months. No survival difference was observed in patients with or without HBV reactivation. (MST: undefined vs 22.4 months, log-rank test: P=0.614).ConclusionHBV reactivation could occur in HBV-related HCC patients who treated with TACE in combination with TKIs plus ICIs. Before and during the combination treatment, it is necessary to routinely monitor HBV DNA and to take effective prophylactic antiviral therapy.

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 (CLCN7) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies.

Recently, in order to reduce carbon emissions and meet climate change targets set by governments worldwide, which has led to the growth of renewable energy sources, such as wind, solar and hydropower energy, more and more ± 800 kV power lines have been built for more than 1500 km long-distance transmission, and the total and ionized field under it serve as important assessment indicators of an electromagnetic field. To calculate the total electric field and ionized field under UHVDC power lines, based on the upwind difference idea proposed by Takuma, the boundary condition and initial value selection are improved with the Kaptzov hypothesis as the boundary condition, and the difference between the surface field strength on the wire and the critical coronal voltage is used as the benchmark to estimate the initial value of charge density. By adopting the improved method, the calculation results of the total electric field and ionized field under the ± 800 kV power lines in typical high altitude regions suggest that the total electric field on the ground increases with the decrease in the wire’s height above ground, while the ion current density goes up with the reduction in the roughness coefficient of the wire; when the ± 800 kV power lines stipulated by national standards go through the residential areas, and the wire’s minimum height above ground is 21 m, total electric field and ionized field under the power lines are less than the limits set by national standards. Also, the calculation method proposed in this paper is suitable for the calculation of ground total electric field for future ± 1,200 kV power lines, which can provide reference for UHVDC power line designing and carbon emission target realization.

Short stature (OMIM: 165800) is a common pediatric disorder. Any abnormality in the cartilage formation of the growth plate can cause short stature. Aggrecan, encoded by ACAN, is an important component of the extracellular matrix. Mutations in ACAN have been reported to cause short stature. In the present study, we enrolled a Chinese family with short stature and advanced bone age across three generations. Whole-exome sequencing (WES) was performed on the proband to detect the candidate genes causing short stature in family. A novel heterozygous frameshift mutation (NM_013227.3:c.7230delT; NP_001356197.1: p. Phe2410Leufs*9) of the ACAN gene was confirmed to be a genetic lesion in this family. This variant, which was located in a functional site globular 3 (G3) domain of ACAN and predicted to be deleterious by informatics programs, was co-segregated with the affected family members by performing Sanger sequencing. Literatures review of growth hormone (GH) treatment outcome of all previously reported ACAN patients suggesting that the G3 domain of ACAN may be critical in the development of short stature and growth hormone treatment. These findings not only contribute to the genetic diagnosis and counseling of the family, but will also expand the mutation spectrum of ACAN.

IntroductionParameterizing the process of trees from the comfort zone to mortality during progressive drought is important for, but is not well represented in, vegetation models, given the lack of appropriate indices to gauge the response of trees to droughts. The objective of this study was to determine reliable and readily available tree drought stressindices and the thresholds at which droughts activate important physiological responses.MethodsWe analyzed the changes in the transpiration (T), stomatal conductance, xylem conductance, and leaf health status due to a decrease in soil water availability (SWA), predawn xylem water potential (ψpd), and midday xylem water potential (ψmd) in Robinia pseudoacacia seedlings during progressive drought.ResultsThe results showed that ψmd was a better indicator of drought stress than SWA and ψpd, because ψmd was more closely related to the physiological response (defoliation and xylem embolization) during severe drought and could be measured more conveniently. We derived the following five stress levels from the observed responses to decreasing ψmd: comfort zone (ψmd > -0.9 MPa), wherein transpiration and stomatal conductance are not limited by SWA; moderate drought stress (-0.9 to -1.75 MPa), wherein transpiration and stomatal conductance are limited by drought; high drought stress (-1.75 to -2.59 MPa), wherein transpiration decreases significantly (T< 10%) and stomata closes completely; severe drought stress (-2.59 to -4.02 MPa), wherein transpiration ceases (T< 0.1%) and leaf shedding orwilting is > 50%; and extreme drought stress (< -4.02 MPa), leading to tree mortality due to xylem hydraulic failure.DiscussionTo our knowledge, our scheme is the first to outline the quantitative thresholds for the downregulation of physiological processes in R. pseudoacacia during drought, therefore, can be used to synthesize valuable information for process-based vegetation models.

Freezing stress is one of the most detrimental environmental factors that can seriously impact the growth, development, and distribution of alfalfa (Medicago sativa L.). Exogenous salicylic acid (SA) has been revealed as a cost-effective method of improving defense against freezing stress due to its predominant role in biotic and abiotic stress resistance. However, how the molecular mechanisms of SA improve freezing stress resistance in alfalfa is still unclear. Therefore, in this study, we used leaf samples of alfalfa seedlings pretreatment with 200 μM and 0 μM SA, which were exposed to freezing stress (-10°C) for 0, 0.5, 1, and 2h and allowed to recover at normal temperature in a growth chamber for 2 days, after which we detect the changes in the phenotypical, physiological, hormone content, and performed a transcriptome analysis to explain SA influence alfalfa in freezing stress. The results demonstrated that exogenous SA could improve the accumulation of free SA in alfalfa leaves primarily through the phenylalanine ammonia-lyase pathway. Moreover, the results of transcriptome analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway-plant play a critical role in SA alleviating freezing stress. In addition, the weighted gene co-expression network analysis (WGCNA) found that MPK3, MPK9, WRKY22 (downstream target gene of MPK3), and TGACG-binding factor 1 (TGA1) are candidate hub genes involved in freezing stress defense, all of which are involved in the SA signaling pathway. Therefore, we conclude that SA could possibly induce MPK3 to regulate WRKY22 to participate in freezing stress to induced gene expression related to SA signaling pathway (NPR1-dependent pathway and NPR1-independent pathway), including the genes of non-expresser of pathogenesis-related gene 1 (NPR1), TGA1, pathogenesis-related 1 (PR1), superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), glutathione-S-transferase (GST), and heat shock protein (HSP). This enhanced the production of antioxidant enzymes such as SOD, POD, and APX, which increases the freezing stress tolerance of alfalfa plants.

Transverse aortic constriction (TAC) is a widely-used animal model for pressure overload-induced cardiac hypertrophy and heart failure (HF). The severity of TAC-induced adverse cardiac remodeling is correlated to the degree and duration of aorta constriction. Most studies of TAC are performed with a 27-gauge needle, which is easy to cause a tremendous left ventricular overload and leads to a rapid HF, but it is accompanied by higher mortality attributed to tighter aortic arch constriction. However, a few studies are focusing on the phenotypes of TAC applied with a 25-gauge needle, which produces a mild overload to induce cardiac remodeling and has low post-operation mortality. Furthermore, the specific timeline of HF induced by TAC applied with a 25-gauge needle in C57BL/6 J mice remains unclear. In this study, C57BL/6 J mice were randomly subjected to TAC with a 25-gauge needle or sham surgery. Echocardiography, gross morphology, and histopathology were applied to evaluate time-series phenotypes in the heart after 2, 4, 6, 8, and 12 weeks. The survival rate of mice after TAC was more than 98%. All mice subjected to TAC maintained compensated cardiac remodeling during the first two weeks and began to exhibit heart failure characteristics after 4 weeks upon TAC. At 8 weeks post-TAC, the mice showed severe cardiac dysfunction, hypertrophy, and cardiac fibrosis compared to sham mice. Moreover, the mice raised a severe dilated HF at 12 weeks. This study provides an optimized method of the mild overload TAC-induced cardiac remodeling from the compensatory period to decompensatory HF in C57BL/6 J mice.

The physical and mechanical behavior of alpine meadow in Tibetan Plateau is now attracting widespread attention. In this paper, a series of experiments were conducted to study the influence of roots on hydrothermal behavior of alpine meadow located at Nangqian district, in the east of Tibetan Plateau, China. Root biomass, physical properties and hydrothermal properties were measured at a soil depth of 0–25 cm. The results showed that the root biomass within the depth of 0–15 cm accounts for 86% of the total root biomass. With the increase of soil depth, the root biomass shows a decreasing trend. The hydraulic conductivities and thermal conductivities of alpine meadow soil increase with the decrease of root biomass. There are lower hydraulic conductivity and thermal conductivity of swallow soil (0–5 cm) than that of deep layer soil. For the bottom soil layer, swallow alpine meadow acts as a “cap” and plays a function of ecological barrier of reducing water infiltration and heat transfer. Under the background of global warming, this insight is helpful to understand the relationship between soil hydrothermal properties and natural disasters in Tibetan Plateau.

To assess the effectiveness of endoscopic retrograde appendicitis therapy (ERAT) as a new technique and method for chronic fecalith appendicitis complicated by active ulcerative colitis. A 46-year-old male patient was admitted with right iliac fossa pain, tenderness, and raised inflammatory markers. A computed tomography (CT) scan of his abdomen confirmed a dilated appendix, which is considered chronic fecalith appendicitis combined with active ulcerative colitis. He was treated with an endoscopic retrograde appendicitis therapy procedure. The patient recovered well after the ERAT procedure and was discharged from the hospital in two days. On follow-up one year later, there was no recurrence of pain in his abdomen. In conclusion, ERAT could be seen as a different approach and be favored as a safer and more effective option in treating UC patients with appendicitis, especially those who are later in the course of the disease. Because of the ERAT procedure, such cases can avoid surgery and surgery-related complications. More research and issues must be addressed to demonstrate the efficacy and effectiveness of ERAT in appendicitis combined with UC.

BackgroundThe treatment and prognostic factors of intravenous leiomyomatosis (IVL) remain lacking systematic evidence.MethodsA retrospective study was conducted on IVL patients from the Qilu Hospital of Shandong University, and IVL cases were published in PubMed, MEDLINE, Embase and Cochrane Library databases. Descriptive statistics were used for the basic characteristics of patients. The Cox proportional hazards regression analysis was used to assess the high-risk factors related to the progression-free survival (PFS). The comparison of survival curves was performed by Kaplan–Meier analysis.ResultsA total of 361 IVL patients were included in this study, 38 patients from Qilu Hospital of Shandong University, and 323 patients from the published literature. Age ≤45 years was observed in 173 (47.9%) patients. According to the clinical staging criteria, stage I/II was observed in 125 (34.6%) patients, and stage III/IV was observed in 221 (61.2%) patients. Dyspnea, orthopnea, and cough were observed in 108 (29.9%) patients. Completed tumor resection was observed in 216 (59.8%) patients, and uncompleted tumor resection was observed in 58 (16.1%) patients. Median follow-up period was 12 months (range 0–194 months), and 68 (18.8%) recurrences or deaths were identified. The adjusted multivariable Cox proportional hazard analysis showed age ≤45 years (vs. >45) (hazard ratio [HR] = 2.09, 95% confidence interval [CI] 1.15–3.80, p = 0.016), and uncompleted tumor resection (vs. completed tumor resection) (HR = 22.03, 95% CI 8.31–58.36, p

IntroductionPoplar is a tree species with important production and application value. The symbiotic relationship between poplar and arbuscular mycorrhizal fungi (AMF) has a key role in ecosystem functioning. However, there remain questions concerning the seasonal dynamics of the AMF community in poplar roots, the relationship between AMF and the soil environment, and its ecological function.MethodPoplar roots and rhizosphere soil were sampled at the end of April and the end of October. The responses of AMF communities to season, host age, and host species were investigated; the soil environmental factors driving community changes were analyzed.ResultsThe diversity and species composition of the AMF community were higher in autumn than in spring. Season, host age, host species, and soil environmental factors affected the formation of the symbiotic mycorrhizal system and the AMF community. Differences in the communities could be explained by soil pH, total nitrogen, total phosphorus, total potassium, available potassium, and glomalin content.DiscussionThe AMF community was sensitive to changes in soil physicochemical properties caused by seasonal dynamics, particularly total potassium. The change in the mycorrhizal symbiotic system was closely related to the growth and development of poplar trees.

BackgroundStudies of sex differences in the use and outcomes of endovascular treatment (EVT) for acute ischemic stroke report inconsistent resultsMethodsWe systematically searched PubMed and Embase databases for studies examining sex-specific utilization of EVT for acute ischemic stroke published before 31 December 2021. Estimates were compared by study type: randomized clinical trials (RCTs) and non-RCTs (hospital-based, registry-based or administrative data). Random effects odds ratios (ORs) were generated to quantify sex differences in EVT use. To estimate sex differences in functional outcome on the modified Rankin scale after EVT, the female:male ratio of ORs and 95% confidence intervals (CIs) were obtained from ordinal or binary analysis.Results6,396 studies were identified through database searching, of which 594 qualified for a full review. A total of 51 studies (36 non-RCT and 15 RCTs) reporting on sex-specific utilization of EVT were included, and of those 10 estimated the sex differences of EVT on functional outcomes. EVT use was similar in women and men both in non-RCTs (OR: 1.03, 95% CI: 0.96–1.11) and RCTs (1.02, 95% CI: 0.89–1.16), with consistent results across years of publication and regions of study, except that in Europe EVT treatment was higher in women than men (1.15, 95% CI: 1.13–1.16). No sex differences were found in the functional outcome by either ordinal and binary analyses (ORs 0.95, 95% CI: 0.68–1.32] and 0.90, 95% CI: 0.65–1.25, respectively).ConclusionsNo sex differences in EVT utilization or on functional outcomes were evident after acute ischemic stroke from large-vessel occlusion. Further research may be required to examine sex differences in long-term outcomes, social domains, and quality of life.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=226100, identifier: CRD42021226100.

Economic development and large amounts of industrial production have led to environmental deterioration. The assessment and prediction of water environment capacity (WEC) are crucial supports for water quality target management. Therefore, this study aims to improve WEC via changes in the industrial structure and to analyze the economic changes. For this purpose, the economic efficiency (EE), water use efficiency (WUE), and water treatment efficiency (WTE) are estimated by the EE–SBM (slack-based measure)–DEA (data envelopment analysis) model. Based on the proposed model, the industry is divided into three types: green enterprises, yellow enterprises, and red enterprises. Yellow enterprises and red enterprises are the major supervision subjects, and the spatial distribution of different environmental risks is identified. The WECs of the main canals are analyzed based on dynamic changes in the industrial structure by integrating the 0-D and MIKE11 models. The results showed that after adjusting the industrial structure, the maximum added values of the WEC of chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH3–N), and total phosphorus (TP) are 1,744.66 t/a, 536.14 t/a, 24.81 t/a, and 4.16 t/a, respectively. The results show that the canals (R40, R41, R20, R19, and R17) are overloaded with pollutants and indicate that TN is included as a water environment quality assessment target. Furthermore, after the optimization of the industrial structure, the loss of industrial output value is 174.44 million yuan, and the added value of the environmental economy is 232.12 million yuan. The findings provide important technical support for achieving industrial upgrading and sustainable development.

Coronavirus disease 2019 (COVID-19) was reported to be associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and patients present mostly with respiratory symptoms. There have been an increasing number of reports on oral manifestations, and some of these signs are informative in terms of identifying SARS-CoV-2 infection. The goal of present study was to review and synthesize the clinical characteristics and underlying mechanisms of COVID-19 oral manifestations, as well as to evaluate the factors influencing SARS-CoV-2 infectivity, in order to conduct further in-depth investigations and help clinicians diagnose COVID-19 patients exhibiting oral symptoms.

Zymomonas mobilis is a promising microorganism for industrial bioethanol production. However, ethanol produced during fermentation is toxic to Z. mobilis and affects its growth and bioethanol production. Although several reports demonstrated that the RNA-binding protein Hfq in Z. mobilis contributes to the tolerance against multiple lignocellulosic hydrolysate inhibitors, the role of Hfq on ethanol tolerance has not been investigated. In this study, hfq in Z. mobilis was either deleted or overexpressed and their effects on cell growth and ethanol tolerance were examined. Our results demonstrated that hfq overexpression improved ethanol tolerance of Z. mobilis, which is probably due to energy saving by downregulating flagellar biosynthesis and heat stress response proteins, as well as reducing the reactive oxygen species induced by ethanol stress via upregulating the sulfate assimilation and cysteine biosynthesis. To explore proteins potentially interacted with Hfq, the TEV protease mediated Yeast Endoplasmic Reticulum Sequestration Screening system (YESS) was established in Z. mobilis. YESS results suggested that Hfq may modulate the cytoplasmic heat shock response by interacting with the heat shock proteins DnaK and DnaJ to deal with the ethanol inhibition. This study thus not only revealed the underlying mechanism of enhanced ethanol tolerance by hfq overexpression, but also provided an alternative approach to investigate protein-protein interactions in Z. mobilis.

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is a lncRNA located at the DLK1-MEG3 site of human chromosome 14q32.3. The expression of MEG3 in various tumors is substantially lower than that in normal adjacent tissues, and deletion of MEG3 expression is involved in the occurrence of many tumors. The high expression of MEG3 could inhibit the occurrence and development of tumors through several mechanisms, which has become a research hotspot in recent years. As a member of tumor suppressor lncRNAs, MEG3 is expected to be a new target for tumor diagnosis and treatment. This review discusses the molecular mechanisms of MEG3 in different tumors and future challenges for the diagnosis and treatment of cancers through MEG3.

BackgroundFactors that may influence the recovery of patients with confirmed SARS-CoV-2 infection hospitalized in the Fangcang shelter were explored, and machine learning models were constructed to predict the duration of recovery during the Omicron BA. 2.2 pandemic.MethodsA retrospective study was conducted at Hongqiao National Exhibition and Convention Center Fangcang shelter (Shanghai, China) from April 9, 2022 to April 25, 2022. The demographics, clinical data, inoculation history, and recovery information of the 13,162 enrolled participants were collected. A multivariable logistic regression model was used to identify independent factors associated with 7-day recovery and 14-day recovery. Machine learning algorithms (DT, SVM, RF, DT/AdaBoost, AdaBoost, SMOTEENN/DT, SMOTEENN/SVM, SMOTEENN/RF, SMOTEENN+DT/AdaBoost, and SMOTEENN/AdaBoost) were used to build models for predicting 7-day and 14-day recovery.ResultsOf the 13,162 patients in the study, the median duration of recovery was 8 days (interquartile range IQR, 6–10 d), 41.31% recovered within 7 days, and 94.83% recovered within 14 days. Univariate analysis showed that the administrative region, age, cough medicine, comorbidities, diabetes, coronary artery disease (CAD), hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were associated with a duration of recovery within 7 days. Age, gender, vaccination dose, cough medicine, comorbidities, diabetes, CAD, hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were related to a duration of recovery within 14 days. In the multivariable analysis, the receipt of two doses of the vaccination vs. unvaccinated (OR = 1.118, 95% CI = 1.003–1.248; p = 0.045), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.114, 95% CI = 1.004–1.236; p = 0.043), diabetes (OR = 0.383, 95% CI = 0.194–0.749; p = 0.005), CAD (OR = 0.107, 95% CI = 0.016–0.421; p = 0.005), hypertension (OR = 0.371, 95% CI = 0.202–0.674; p = 0.001), and ratio of N/IC (OR = 3.686, 95% CI = 2.939–4.629; p < 0.001) were significantly and independently associated with a duration of recovery within 7 days. Gender (OR = 0.736, 95% CI = 0.63–0.861; p < 0.001), age (30–70) (OR = 0.738, 95% CI = 0.594–0.911; p < 0.001), age (>70) (OR = 0.38, 95% CI = 0292–0.494; p < 0.001), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.391, 95% CI = 1.12–1.719; p = 0.0033), cough medicine (OR = 1.509, 95% CI = 1.075–2.19; p = 0.023), and symptoms (OR = 1.619, 95% CI = 1.306–2.028; p < 0.001) were significantly and independently associated with a duration of recovery within 14 days. The SMOTEEN/RF algorithm performed best, with an accuracy of 90.32%, sensitivity of 92.22%, specificity of 88.31%, F1 score of 90.71%, and AUC of 89.75% for the 7-day recovery prediction; and an accuracy of 93.81%, sensitivity of 93.40%, specificity of 93.81%, F1 score of 93.42%, and AUC of 93.53% for the 14-day recovery prediction.ConclusionAge and vaccination dose were factors robustly associated with accelerated recovery both on day 7 and day 14 from the onset of disease during the Omicron BA. 2.2 wave. The results suggest that the SMOTEEN/RF-based model could be used to predict the probability of 7-day and 14-day recovery from the Omicron variant of SARS-CoV-2 infection for COVID-19 prevention and control policy in other regions or countries. This may also help to generate external validation for the model.

BackgroundA thoracogastric airway fistula (TGAF) is a rare and potentially fatal complication of esophagectomy for esophageal and cardia carcinomas. Isolation of the fistula and pulmonary separation is necessary during the surgical repair of a tracheal fistula. However, currently, the reported airway management techniques are not suitable for patients with a large TGAF. This case study presents an alternative technique for performing differential lung ventilation in a patient with a thoracogastric airway fistula.Case presentationA 70-year-old man was diagnosed with a thoracogastric airway fistula situated above the carina after esophagectomy, and a thoracoscope-assisted repair of the fistula and pectoralis major myocutaneous flap transplantation were scheduled. The patient could not tolerate one-lung ventilation and the complex intubating operation due to aspiration pneumonia and the size (3.5 cm × 1.7 cm) of the fistula. We, therefore, performed differential lung ventilation in which an extended 6.5#single-lumen endotracheal tube was inserted into the left main bronchus and a 9Fr bronchial blocker was placed in the right main bronchus by using the video-flexible intubation scope. The right lung was selectively inflated with jet ventilation, while positive pressure ventilation was maintained through the left endotracheal tube. The value of SPO2 remained above 95% throughout the operation.ConclusionFor patients with a large thoracogastric airway fistula, differential lung ventilation of a combination of positive pressure ventilation and jet ventilation is useful. Inserting an extended single-lumen endotracheal tube into the left main bronchus and a bronchial blocker into the right main bronchus could be another way of providing differential ventilation for patients with a large thoracogastric airway fistula.

Purpose: A systematic review and meta-analysis was conducted to combine the data available from clinical trials and evaluate the clinical efficacy and safety of tirzepatide in people with type 2 diabetes (T2D).Methods: We systematically searched the MEDLINE, Embase, Cochrane Library, and clinical trials registries (https://clinicaltrials.gov) up to 25 March 2022 for randomized controlled trials (RCTs) that compared tirzepatide with placebo or active hypoglycemic drugs in subjects with T2D. Heterogeneity was judged by the I2 value and Cochran’s Q test. The randomized effects model was adopted to calculate risk ratios and weighted mean differences (WMDs). The primary outcome was the change from baseline in HbA1c levels. Secondary efficacy endpoints were fasting serum glucose (FSG), change of body weight, blood pressure, fasting lipid profiles, and safety indexes.Results: Six trials comprising 6,579 subjects (4,410 in the tirzepatide group and 2,054 in the control group) fulfilled the pre-specified criteria and were included in the study. Tirzepatide treatment resulted in reducing HbA1c (WMD: -1.07%; 95% confidence intervals [CIs]: −1.44, −0.56), FSG (WMD, −21.50 mg/dl; 95% CI: −34.44, −8.56), body weight (WMD: −7.99 kg; 95% CI −11.36, −4.62), and blood pressure and ameliorated fasting lipid profiles, without increasing hypoglycemia, either as monotherapy or an add-on therapy. Tirzepatide increased the risk of gastrointestinal adverse events mainly in add-on therapy but not in terms of pancreatitis or cholelithiasis. Furthermore, tirzepatide presented a dose–response effect on the reduction in HbA1c and body weight and increase in nausea and vomiting.Conclusion: In patients with type 2 diabetes, tirzepatide shows superior blood glucose control and weight loss performance, without an increased risk of hypoglycemia.Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO), identifier (CRD42022319442).

During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine type diseases and transmissions has occurred. However, it is necessary to develop a less expensive, serotype-independent pneumococcal vaccine due to the emergence of nonvaccine-type pneumococcal diseases and the limited effect of vaccines on colonization. As next-generation vaccines, conserved proteins, such as neuraminidase A (NanA), elongation factor Tu (Tuf), and pneumolysin (Ply), are promising targets against pneumococcal infections. Here, we designed and constructed a novel fusion protein, NanAT1-TufT1-PlyD4, using the structural and functional domains of full-length NanA, Tuf and Ply proteins with suitable linkers based on bioinformatics analysis and molecular cloning technology. Then, we tested whether the protein protected against focal and lethal pneumococcal infections and examined its potential protective mechanisms. The fusion protein NanAT1-TufT1-PlyD4 consists of 627 amino acids, which exhibits a relatively high level of thermostability, high stability, solubility and a high antigenic index without allergenicity. The purified fusion protein was used to subcutaneously immunize C57BL/6 mice, and NanAT1-TufT1-PlyD4 induced a strong and significant humoral immune response. The anti-NanAT1-TufT1-PlyD4 specific IgG antibody assays increased after the first immunization and reached the highest value at the 35th day. The results from in vitro experiments showed that anti-NanAT1-TufT1-PlyD4 antisera could inhibit the adhesion of Streptococcus pneumoniae (S. pneumoniae) to A549 cells. In addition, immunization with NanAT1-TufT1-PlyD4 significantly reduced S. pneumoniae colonization in the lung and decreased the damage to the lung tissues induced by S. pneumoniae infection. After challenge with a lethal dose of serotype 3 (NC_WCSUH32403), a better protection effect was observed with NanAT1-TufT1-PlyD4-immunized mice than with the separate full-length proteins and the adjuvant control; the survival rate was 50%, which met the standard of the marketed vaccine. Moreover, we showed that the humoral immune response and the Th1, Th2 and Th17-cellular immune pathways are involved in the immune protection of NanAT1-TufT1-PlyD4 to the host. Collectively, our results support that the novel fusion protein NanAT1-TufT1-PlyD4 exhibits extensive immune stimulation and is effective against pneumococcal challenges, and these properties are partially attributed to humoral and cellular-mediated immune responses.

Respiratory syncytial virus (RSV) is a ubiquitous pathogen of viral bronchiolitis and pneumonia in children younger than 2 years of age, which is closely associated with recurrent wheezing and airway hyperresponsiveness (AHR). Alveolar macrophages (AMs) located on the surface of the alveoli cavity are the important innate immune barrier in the respiratory tract. AMs are recognized as recruited airspace macrophages (RecAMs) and resident airspace macrophages (RAMs) based on their origins and roaming traits. AMs are polarized in the case of RSV infection, forming two macrophage phenotypes termed as M1-like and M2-like macrophages. Both M1 macrophages and M2 macrophages are involved in the modulation of inflammatory responses, among which M1 macrophages are capable of pro-inflammatory responses and M2 macrophages are capable of anti-proinflammatory responses and repair damaged tissues in the acute and convalescent phases of RSV infection. Polarized AMs affect disease progression through the alteration of immune cell surface phenotypes as well as participate in the regulation of T lymphocyte differentiation and the type of inflammatory response, which are closely associated with long-term AHR. In recent years, some progress have been made in the regulatory mechanism of AM polarization caused by RSV infection, which participates in acute respiratory inflammatory response and mediating AHR in infants. Here we summarized the role of RSV-infection-mediated AM polarization associated with AHR in infants.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).Method: A total of 104 patients with primary HCC, admitted to People’s Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8 weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15 min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8 weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients.Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6 months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18 months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival.Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

ObjectiveTo evaluate the radiologic parameters of degenerative lumbar spondylolisthesis (DLS) and determine the radiographic risk factors for DLS by making comparisons with healthy control subjects.MethodsSeventy-five patients with L4/5 DLS (Meyerding grade I) and 53 healthy control subjects were analyzed. The L1-S1 disc height index (DHI), L4/5 facet joint angle (FJA), and relative cross-sectional area (RCSA) of paravertebral muscles were measured in both groups. The initial L4/5 DHI (iDHI) before the onset of DLS were estimated based on the L3/4 DHI of the DLS group and DHI of the control group. The sagittal parameters of DLS were also included in this study.ResultsThe DHI of L4/5 was lower in the DLS group than in the control group (P

Intestinal bowel disease (IBD) has always been tough to treat, therefore researchers are struggle to look for treatments that are safe, low cost, and effective. Food-derived peptides are thought to have anti-inflammatory and antioxidant properties, but they have not been studied in depth in the treatment of IBD. Based on this, we explored the effect of tilapia skin peptides (TSPs) on the remission of colitis in the present study. Colonic epithelial cell lines CT-26 and HT-29 were co-treated with lipopolysaccharide (LPS) and TSPs for 12 h. Cell viability was assessed by CCK8 assay. Dextran sulfate sodium (DSS)-induced colitis model was established and 100 mg/kg TSPs were oral administered at the same time as DSS intervention. Colonic mucosal barrier function was assessed by western blotting. The inflammatory responses were evaluated by quantitative real-time PCR along with ELISA, respectively. Apoptosis was investigated by TUNEL and flow cytometry. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to characterize peptides composition of TSPs. It was found that TSPs significantly inhibit LPS-induced inflammation and apoptosis in vitro without affecting cell viability. Moreover, the upregulation and activation of Caspase-3 and Caspase-8 were also reversed by TSPs. Subsequently, in vivo experiments demonstrated that TSPs can attenuate DSS induced colitis, manifested by a decrease in weight loss and colon shortening. The expression of ZO-1 and occluding were significantly increased, and the pro-inflammatory cytokines were down-regulated. Meanwhile, TSPs alleviated DSS-induced apoptosis and reduced the expressions of Caspase-3 and Caspase-8. Finally, we found that TSPs were composed of 51 short peptides, and 12 of them were predicted to have significant biological activity. Collectively, this study suggested that TSPs can alleviate colon damage caused by foreign stimuli via inhibiting inflammation and apoptosis which indicated that it has great potential value for the treatment of IBD.

Pneumocystis pneumonia (PCP) is an opportunity acquired infection, which is usually easy to occur in patients with AIDS, organ transplantation, and immunosuppressive drugs. The prevention and treatment must be necessary for PCP patients with immunocompromise. And the oxidants are currently a typical regimen, including sulfanilamide, dapsone, primaquine, etc. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked gene-disease that affects about 400 million people worldwide. The lack of G6PD in this population results in a decrease in intracellular glutathione synthesis and a weakening of the detoxification ability of the oxidants. As a result, oxidants can directly damage haemoglobin in red blood cells, inducing methemoglobin and hemolysis. When patients with G6PD deficiency have low immunity, they are prone to PCP infection, so choosing drugs that do not induce hemolysis is essential. There are no clear guidelines to recommend the drug choice of this kind of population at home and abroad. This paper aims to demonstrate the drug choice for PCP patients with G6PD deficiency through theoretical research combined with clinical cases.

Advanced adiabatic compressed air energy storage (AA-CAES) is a promising form of CAES technology, which can realize multi-energy cascade storage and supply. Given the characteristics of cooling, heating, and power (CHP) load demand of regionally integrated energy system (IES) and the overall need to control the total carbon emission, this study first establishes the AA-CAES multi-energy storage model; second, based on analyzing the multi-energy characteristics of AA-CAES, a ladder-type carbon trading mechanism is introduced; furthermore, aiming for minimal system operating costs and carbon trading costs, an optimal dispatch model of an integrated energy system with AA-CAES as the energy hub for coupling multiple energy forms is established. Finally, an empirical study was conducted based on the energy use scenario of a provincial and ministerial university in Qinghai Province. This study analyzes the impact of the operation of AA-CAES and the introduction of ladder-type carbon trading on the operating costs and carbon trading costs of IES. The simulation results show that the total operating cost of the proposed model is reduced by 23.9%, and carbon emission is decreased by 14.5% compared to the conventional IES. It proves the validity of coupling AA-CAES and stepped carbon trading mechanisms to facilitate low-carbon economy in IES.

BackgroundProstate cancer (PCa) is a serious threat to the health of elderly aged groups. It is very important to understand the occurrence and development of PCa for early diagnosis, treatment and metastasis control. This study aims to elucidate the international frontier research direction and literature distribution through bibliometric and visual analyses of PCa bone metastasis.MethodsData were obtained from the Web of Science core collection database, which collected 2,246 papers related to PCa bone metastasis from 1 January 2012 to 31 December 2021. The collected data were analyzed using the VOSviewer software for citation, co-authorship, co-citation, bibliometric coupling, and co-occurrence.ResultsOver the past decade, published papers have increased annually. The United States of America has published 890 papers with 29,161 citations, far more than any other country, and it has the most extensive collaboration with other countries. For example, 33 articles by Saad Fred were cited 2,721 times, and 91 articles from the University of Texas MD Anderson CANC CTR were cited 3,037 times, the most cited author and organization. Peng Xinsheng and Duke UNIV comprise the most active collaborative author and organization, respectively. The most co-cited journal was CANCER RES, with 3,195 citations. Studies of PCa bone metastasis can be divided into four categories: “basic research,” “auxiliary diagnosis and treatment,” “clinical trial,” and “prognosis.”ConclusionOur results provide a comprehensive overview of the research priorities and future directions of PCa bone metastasis, which can further accurately guide researchers in diagnosis, treatment, and personalized prevention.

In order to study the regulation of Fenugreek seed extract (FSE) on the immunity of broilers, and explore the appropriate amount of FSE in broilers' production, 1-day-old yellow feather broilers with a total of 420 birds were randomly allocated into seven treatments. Each treatment had six replicates, with 10 birds per replicate. The two control groups were the basic fodder group fed with basal diet and the bacitracin zinc group added 30 mg/kg bacitracin zinc to the basal diet. Experimental groups included five levels of FSE (50, 100, 200, 400, and 800 mg/kg FSE to the basal diet, respectively). The pre-test period was 7 days and the formal test lasted for 56 days. The results showed that the average daily gain (ADG) of 50 and 800 mg/kg FSE groups was significantly increased (P < 0.01), and the feed to gain ratio (F/G) of FSE groups was significantly decreased (P < 0.01) compared with the basic fodder and the bacitracin zinc groups. Compared with the basic fodder group, the serum total cholesterol (TC) content in the FSE groups was significantly decreased (P < 0.05), the serum low density lipoprotein cholesterol (LDL-C) content of 50, 100, and 800 mg/kg FSE groups was significantly lower than that of the basic fodder group (P < 0.05). Compared with the basic fodder and bacitracin zinc groups, the serum immunoglobulins (IgG, IgM, IgA) content of 100 and 200 mg/kg FSE groups were significantly increased (P < 0.05). Compared with the bacitracin zinc group, the serum interleukins (IL-1, IL-10) content of 400 mg/kg FSE group were significantly increased (P ≤ 0.05), and the serum interferon-γ (IFN-γ) content of 100 and 200 mg/kg FSE groups was significantly increased (P < 0.05). Compared with the basic fodder group, the lower doses (0–400 mg/kg) of FSE had no significant effect on the mRNA expression of toll-like receptors 4/ myeloid differentiation factor 88/ nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathways (P > 0.05). The 800 mg/kg FSE treatment group significantly increased the expression levels of nuclear factor-κB (NF-κB) mRNA in the spleen of broilers (P < 0.05). The zinc bacitracin group significantly increased the expression levels of myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) mRNA (P ≤ 0.05). The results showed that FSE could promote the secretion of immunoglobulins, regulate the body's cytokines, and have a positive effect on immunity in broilers. Furthermore, the recommended supplement of FSE is 100 mg/kg in the broiler diet.