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Limiting climate change to 1.5°C and achieving net-zero emissions would entail substantial carbon dioxide removal (CDR) from the atmosphere by the mid-century, but how much CDR is needed at country level over time is unclear. The purpose of this paper is to provide a detailed description of when and how much CDR is required at country level in order to achieve 1.5°C and how much CDR countries can carry out domestically. We allocate global CDR pathways among 170 countries according to 6 equity principles and assess these allocations with respect to countries biophysical and geophysical capacity to deploy CDR. Allocating global CDR to countries based on these principles suggests that CDR will, on average, represent ∼4% of nations total emissions in 2030, rising to ∼17% in 2040. Moreover, equitable allocations of CDR, in many cases, exceed implied land and carbon storage capacities. We estimate ∼15% of countries (25) would have insufficient land to contribute an equitable share of global CDR, and ∼40% of countries (71) would have insufficient geological storage capacity. Unless more diverse CDR technologies are developed, the mismatch between CDR liabilities and land-based CDR capacities will lead to global demand for six GtCO2 carbon credits from 2020 to 2050. This demonstrates an imperative demand for international carbon trading of CDR.

Objective To evaluate the influencing factors of fear of disease progression and examine its impact on quality-of-life in non-dialysis patients with chronic kidney disease （CKD） in stages 3-5. Methods From June 2022 to May 2023, 130 non-dialysis CKD patients in stages 3-5 were examined by Fear of Progression Questionnaire-Short Form （FoP-Q-SF） and Mos 36-item short-form health survey （SF-36）. General demographics and clinical related parameters were recorded. Degree of FoP, its influencing factors and correlation with quality-of-life were explored. Results Average score of FoP-Q-SF was （32.84 ± 6.13） and 43.84% of them fulfilled the dysfunctional fear of progression criterion （score≥34）. Multiple stepwise linear regression analysis indicated that age （t = −2.024）, education level （t = −2.690）, emotional state （t = 6.808）, disease stage （t = 2.134） and abnormal calcium & phosphorus metabolism （t = −2.099） were the influencing factors for fear of disease progression （P＜0.05）. Quality-of-life scores of CKD patients were lower than those of Chinese normative scores and quality-of-life was lower. In patients with FoP-Q-SF score equal or greater than 34 points, scores of each dimension of SF-36 scale were significantly lower than those with FoP-Q-SF score ＜34 points （P＜0.05）. A significant negative correlation existed between FoP and quality-of-life in non-dialysis CKD patients in stages 3-5. Conclusion In patients with non-dialysis CKD, fear of disease progression seriously affects their quality-of-life. It is correlated with age, education level, emotional state, disease stage and abnormal calcium & phosphorus metabolism. Physicians should devote greater efforts to health education and social supports.

The substitutional structure of cyclotriphosphazene derivatives significantly influences their flame-retardant effectiveness. A cyclotriphosphazene derivative with triazole group, referred to as hexa(1,2,4-triazol-3-ylamine) cyclotriphosphazene (HATA), was utilized to improve the flame retardancy of epoxy resin (EP). Differential scanning calorimetry, thermogravimetric analysis, and dynamic mechanical analysis were employed to characterize the thermal properties of EP/HATA thermosets. HATA facilitated the curing of EP due to its triazole and secondary amine structure. EP/HATA thermosets exhibited improved char-forming ability and storage modulus, attributed to the rigid cyclophosphonitrile structure of HATA. As a result of incorporating 5% HATA with 0.73 wt% phosphorus, EP passed UL-94 V-0 level. Subsequent analysis using a cone calorimeter revealed obvious reductions in the peak heat release rate, fire growth rate, and total smoke production of EP with the addition of HATA. Simultaneously, there was a significant enhancement in the char yield of EP during combustion, indicating notable improvements in fire safety. Additional investigations, including X-ray photoelectron spectroscopy, scanning electron microscopy, TG-FTIR, and pyrolysis gas chromatography/mass spectrometry, were employed to analyze the char residue and gaseous volatiles. HATA promoted the formation of a dense, continuous, and intumescent char layer containing cyclophosphonitrile structure in EP. Moreover, the decomposition of HATA released a notable quantity of nitrogen-containing volatiles, effectively mitigating flammable gases originating from the EP matrix in gaseous phase. A biphasic flame-retardant mode of action was proposed, underscoring cooperative flame-retardant effects arising from the interaction between triazole substituents and cyclophosphonitrile structure in HATA molecular for EP.

Abstract Introduction Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials. Methods This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics. Results In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104. Conclusion This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.

Due to concerns about carbon leakage and sectoral competitiveness, the European Union (EU) proposed implementing the carbon border adjustment mechanism (CBAM). The effectiveness and potential negative consequences of CBAM have aroused extensive discussion. From the perspective of the economy-wide analysis, this study uses a global computable general equilibrium model to explore the rationality of CBAM from the aspects of socioeconomic impact and the effects of promoting climate mitigation. Furthermore, the potential alternative mechanism of CBAM is proposed. The results show that CBAM can reduce the EU's gross domestic product (GDP) loss; however, the GDP loss in all other regions increases. Moreover, CBAM raises household welfare losses in most regions, including the EU. Second, although CBAM can reduce the marginal abatement cost in eight regions, it comes at the cost of greater economic losses. Furthermore, the economic and household welfare cost of raising emissions reduction targets in regions like the USA and Japan is substantially higher than the impact of passively accepting the CBAM; therefore, CBAM's ability to drive ambitious emission reduction initiatives may be limited. Finally, for the potential alternative mechanism, from the perspective of reducing economic cost and household welfare losses, the EU could implement domestic tax cuts in the short-term and promote global unified carbon pricing in the long-term.

Abstract Background Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. Methods We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. Results We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. Conclusions This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future. Graphical Abstract

In order to realize the few shot font generation, local component method usually ignores the role of component location information on text generation, resulting in the deviation of the overall structure layout of the generated text. In order to capture component location information effectively, a method of few shot font generation by integrating component position information features (CPI-Font) is proposed. The proposed CPI-Font model takes MX-Font as the basic framework to design a new global location information extractor. The global position information is extracted with coordinate attention, and different importance of each component in the global position information is paid attention to by multi-component attention, so as to capture the global position relation features of local components in the whole glyphs and avoid the deviation of the generated glyphs structure. Using 39 publicly constructed fonts as Chinese character datasets, a large number of experiments are carried out with the current mainstream models. Experimental results show that the proposed model achieves 0.112 in LPIPS value, 88.5 in FID value, and 83.1% and 70.4% in content and style accuracy, respectively. The model is superior to other algorithms in three evaluation indices. The results show that the CPI-Font model can capture the location information of components effectively and has a relatively advanced performance of the few shot font generation.

Abstract Introduction Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed ‘BARI itch-dominant’ patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. Methods BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. Results BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%–40.3%), highest in the head and neck, mean EASI region scores of 15.7–24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4–2.3, out of 3), especially for erythema. Conclusion BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population.

In the present study, the complete mitochondrial genome (mitogenome) of the Papilio macilentus (Lepidoptera: Papilionoidea: Papilionidae) was sequenced by next-generation sequencing method. The mitochondrial genome is a circular DNA molecule of 15,264 bp in size with 80.7% AT content, including 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and a long non-coding region (Control region). All protein-coding genes are initiated by ATN codons, and terminated with TAA, TAG, or single T. All tRNAs can be folded into common clover leaf secondary structure, except trn-S1. Phylogenetic analyses based on 13 protein-coding genes and 2 rRNA genes using maximum likelihood and Bayesian inference confirmed that P. macilentus and Papilio memnon are clustered into a clade, and revealed the relationships between Papilionini, Troidini, Teinopaippini and Leptocircini.

Abstract Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Abstract Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33–104.96% for the maximum plasma concentration (Cmax), 97.21–102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0–t), and 97.22–102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0–∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28–110.69% for the minimal BIS value (BISmin), 99.23–101.17% for the area under the BIS time curve from time 0–60 min after administration (BISAUC0–60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00–125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance. Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

Abstract Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

Abstract Background The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. Methods This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8–10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students’ body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. Discussion The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. Trial registration Clinicaltrials.gov NCT05482191. Registered on July 2022.

Abstract Background The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes. Methods In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR

Abstract Background Alopecia areata (AA) is an autoimmune hair loss disorder associated with high rates of emotional and psychosocial distress. Baricitinib, an oral selective Janus kinase (JAK) 1 and JAK 2 inhibitor, was superior to placebo with respect to hair regrowth in two phase 3 trials involving 1200 adults with severe AA (≥50% of scalp hair loss). Objectives This analysis investigated the evolution of health‐related quality of life (HRQoL) and symptoms of anxiety and depression after treatment with baricitinib in severe AA. Methods Patients were randomized to placebo, baricitinib 2‐mg, or baricitinib 4‐mg. Improvements in HRQoL and psychological burden were measured using Skindex‐16 AA and Hospital Anxiety and Depression Scales (HADS‐A and HADS‐D), respectively. Changes from baseline through Week 36 were analyzed using analysis of covariance with modified last observation carried forward for missing data. Proportion of patients with baseline HADS score ≥8 that shifted to

BackgroundAbout 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV.MethodsIn this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed.ResultsTotally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV.ConclusionsHigh HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

Magnetic induction hyperthermia (MIH), is a technique that has developed rapidly in recent years in the field of tumor thermotherapy. It implants a magnetic heating medium (millimeter-sized heat seeds, micron-sized magnetic particles and nanometer-sized magnetic fluids, etc.) inside the tumor. The material heats up under the induction of an external alternating magnetic field (100–500 kHz), which causes a high temperature zone to rapidly form in the local biological tissues and induces apoptosis in tumor cells. Magnetic induction hyperthermia has the advantages of high safety, strong targeting, repeatable treatment, and the size of the incision during treatment is negligible compared to surgical resection, and is currently used in clinical treatment. However, the millimeter-scale heat seed heating that is typically used in treatments can result in uneven temperatures within the tissue. Common MIH heating devices are bulky and complex in design, and are not easy for medical staff to get their hands on, which are issues that limit the diffusion of MIH. In this view, this paper will discuss the basic theoretical research on MIH and the progress of MIH-related technologies, with a focus on the latest research and development results and research hotspots of nanoscale ferromagnetic media and magnetic heat therapy devices, as well as the validation results and therapeutic efficacy of the new MIH technology on animal experiments and clinical trials. In this paper, it is found that induction heating using magnetic nanoparticles improves the uniformity of the temperature field, and the magneto-thermal properties of nanoscale ferromagnetic materials are significantly improved. The heating device was miniaturized to simplify the operation steps, while the focusing of the magnetic field was locally enhanced. However, there are fewer studies on the biotoxicity aspects of nanomedicines, and the localized alternating magnetic field uniformity used for heating and the safety of the alternating magnetic field after irradiation of the human body have not been sufficiently discussed. Ultimately, the purpose of this paper is to advance research related to magnetic induction thermotherapy that can be applied in clinical treatment.

IntroductionWe previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models.MethodsATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson’s disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish.ResultsCells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson’s disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio.ConclusionThis study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

With the improvement of national health awareness and the popularization of a series of screening methods, the number of patients with early colorectal cancer is gradually increasing, and accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determining the optimal therapeutic solutions. Whether patients with T1 colorectal cancer undergoing endoscopic resection require additional surgery and regional lymph node dissection is inconclusive in current guidelines. However, we can be sure that in early colorectal cancer without lymph node metastasis, endoscopic resection alone does not affect the prognosis, and it greatly improves the quality of life and reduces the incidence of surgical complications while preserving organ integrity. Therefore, it is vital to discriminate patients without lymph node metastasis in T1 colorectal cancer, and this requires accurate predictors. This paper briefly explains the significance and shortcomings of traditional pathological factors, then extends and states the new pathological factors, clinical test factors, molecular biomarkers, and the risk assessment models of lymph node metastasis based on artificial intelligence.

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.05) accompanied by γH2AX positivity in >95 % tumor cells in tumor core and >85 % in the invasive foci as well as ∼30 % apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species accumulation, were detected together with the enrichment of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies.

Background Colletotrichum species are among the most common pathogens in agriculture and forestry, and their control is urgently needed. Methods In this study, a total of 68 strains of biocontrol bacteria were isolated and identified from Photinia × fraseri rhizosphere soil. Results The isolates were identified as Brevibacillus brevis by 16S rRNA. The inhibitory effect of TR-4 on Colletotrichum was confirmed by an in vitro antagonistic experiment. The inhibitory effect of TR-4 was 98% at a concentration of 10 µl/ml bacterial solution, protection of the plant and inhibition of C. siamense was evident. Moreover, the secretion of cellulase and chitosan enzymes in the TR-4 fermentation liquid cultured for three days was 9.07 mol/L and 2.15 µl/mol, respectively. Scanning electron microscopy and transmission electron microscopy confirmed that TR-4 destroyed the cell wall of C. siamense, resulting in leakage of the cell contents, thus weakening the pathogenicity of the bacteria.

IntroductionPathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China.MethodsThrough a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020.ResultsBased on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes.DiscussionThis systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.

ObjectiveTo investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted.MethodsStudents in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression.ResultsOf the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one’s education.ConclusionsSuicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Lasers operating around 2-µm have been extensively researched for various applications, such as LiDAR, remote sensing, optical communication, and medicine. One of the approaches to generate 2-µm emission is to employ an optical parametric oscillator pumped by 1-µm laser; however, improving the 2-µm laser conversion efficiency of optical parametric oscillators is still a challenge. In this study, we exploit the high nonlinear coefficient of the KTP crystal at the 2-µm band to realize a high-efficiency optical parametric oscillator. The OPO is driven by a laser diode (LD) side-pumped, electro-optic Q-modulated Nd:YAG laser. The cavity was designed and optimized based on mode matching to increase the peak power density of the pump laser. Different powers were obtained for different pump laser focusing conditions, and the maximum power was obtained when the KTP crystal was placed in front of the pump laser focus. The output characteristics of the KTP at different phase-matching angles were also investigated. An output power of 2.44 W and an output pulse width of 9.04 ns were obtained at 2154.4 nm with an optical-to-optical conversion efficiency of 23.39% and a slope efficiency of 36.09%.