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Abstract Under the target of ‘emission peak and carbon neutrality’, electricity distribution networks will massively access low‐carbon technologies, which will result in problems such as insufficient hosting capacity, unbalanced electricity loads, degraded power quality etc. The low‐voltage flexible distribution network (LVFDN), which interconnects its low‐voltage service transformers using flexible power electronic devices (flexible interconnected devices [FIDs]) is considered an effective means to deal with the challenges above. The total supply capability (TSC) of LVFDN is proposed. Firstly, the typical structures of LVFDN and their operation modes are proposed. Then, the TSC model of LVFDN, which formulates flexible power flow control and multi‐level (medium‐voltage feeder and low‐voltage flexible interconnection) load transfer is proposed. Due to the non‐linear non‐convex characteristics of the proposed TSC model, a new algorithm based on the ‘branch and bound algorithm’ is also provided. In the case study, the TSC of an actual electricity distribution network is calculated and tested by the N‐1 verification method. Finally, the variations of TSC with different capacities of the low‐voltage FID are analysed. Suggestions for the planning and operation of LVFDN are also given. A theoretical basis for the application of flexible interconnection technology in low‐voltage electricity distribution networks is provided.

Abstract Background Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. Results In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. Conclusions These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Abstract The global energy budget is pivotal to understanding planetary evolution and climate behaviors. Assessing the energy budget of giant planets, particularly those with large seasonal cycles, however, remains a challenge without long-term observations. Evolution models of Saturn cannot explain its estimated Bond albedo and internal heat flux, mainly because previous estimates were based on limited observations. Here, we analyze the long-term observations recorded by the Cassini spacecraft and find notably higher Bond albedo (0.41 ± 0.02) and internal heat flux (2.84 ± 0.20 Wm−2) values than previous estimates. Furthermore, Saturn’s global energy budget is not in a steady state and exhibits significant dynamical imbalances. The global radiant energy deficit at the top of the atmosphere, indicative of the planetary cooling of Saturn, reveals remarkable seasonal fluctuations with a magnitude of 16.0 ± 4.2%. Further analysis of the energy budget of the upper atmosphere including the internal heat suggests seasonal energy imbalances at both global and hemispheric scales, contributing to the development of giant convective storms on Saturn. Similar seasonal variabilities of planetary cooling and energy imbalance exist in other giant planets within and beyond the Solar System, a prospect currently overlooked in existing evolutional and atmospheric models.

High-energy density dielectrics for electrostatic capacitors are in urgent demand for advanced electronics and electrical power systems. Poly(vinylidene fluoride) (PVDF) based nanocomposites have attracted remarkable attention by intrinsic high polarization, flexibility, low density, and outstanding processability. However, it is still challenging to achieve significant improvement in energy density due to the common contradictions between electric polarization and breakdown strength. Here, we proposed a novel facile strategy that simultaneously achieves the construction of in-plane oriented BaTiO3 nanowires and crystallization modulation of PVDF matrix via an in-situ uniaxial stretch process. The polar phase transition and enhanced Young's modulus facilitate the synergetic improvement of electric polarization and voltage endurance capability for PVDF matrix. Additionally, the aligned distribution of nanowires could reduce the contact probability of nanowire tips, thus alleviating electric field concentration and hindering the conductive path. Finally, a record high energy density of 38.3 ​J/cm3 and 40.9 ​J/cm3 are achieved for single layer and optimized sandwich-structured nanocomposite, respectively. This work provides a unique structural design and universal method for dielectric nanocomposites with ultrahigh energy density, which presents a promising prospect of practical application for modern energy storage systems.

Endoscopic retrograde appendicitis therapy (ERAT) is a novel and minimally invasive technological alternative for the management of acute or chronic appendicitis. Through endoscopic appendiceal intubation, obstructions such as appendiceal feces and parasites within the appendiceal lumen can be effectively eliminated, leading to patient recovery. Additionally, in cases where the orifices are swollen or complicated appendicitis is present, a stent may be inserted following appendiceal flushing. Due to the utilization of endoscopy for accessing the orifices of the appendix in order to alleviate appendiceal obstruction, patients were able to avoid undergoing appendectomy and experienced a reduced likelihood of recurrence when compared to antibiotic therapy. Additionally, the ERAT provided alternative options for individuals with appendicitis and comorbidities. Recent advancements in techniques, such as the “mother–baby” endoscopic system and the use of microbubble contrast agents, have expanded the range of indications and the eligible patient populations. The objective of this review is to present a comprehensive overview of the development, procedural aspects, therapeutic principles, treatment efficacy, therapeutic applications, and potential complications associated with ERAT.

Abstract Background The specific pathogenesis of UC is still unclear, but it has been clear that defects in intestinal barrier function play an important role in it. There is a temporary lack of specific drugs for clinical treatment. Astragaloside IV (AS-IV) is one of the main active ingredients extracted from Astragalus root and is a common Chinese herbal medicine for the treatment of gastrointestinal diseases. This study aimed to determine whether AS-IV has therapeutic value for DSS or LPS-induced intestinal epithelial barrier dysfunction in vivo and in vitro and its potential molecular mechanisms. Methods The intestinal tissues from UC patients and colitis mice were collected, intestinal inflammation was observed by colonoscopy, and mucosal barrier function was measured by immunofluorescence staining. PI3K/AKT signaling pathway activator YS-49 and inhibitor LY-29 were administered to colitic mice to uncover the effect of this pathway on gut mucosal barrier modulation. Then, network pharmacology was used to screen Astragaloside IV (AS-IV), a core active component of the traditional Chinese medicine Astragalus membranaceus. The potential of AS-IV for intestinal barrier function repairment and UC treatment through blockade of the PI3K/AKT pathway was further confirmed by histopathological staining, FITC-dextran, transmission electron microscopy, ELISA, immunofluorescence, qRT-PCR, and western blotting. Finally, 16 S rRNA sequencing was performed to uncover whether AS-IV can ameliorate UC by regulating gut microbiota homeostasis. Results Mucosal barrier function was significantly damaged in UC patients and murine colitis, and the activated PI3K/AKT signaling pathway was extensively involved. Both in vivo and vitro showed that the AS-IV-treated group significantly relieved inflammation and improved intestinal epithelial permeability by inhibiting the activation of the PI3K/AKT signaling pathway. In addition, microbiome data found that gut microbiota participates in AS-IV–mediated intestinal barrier recovery as well. Conclusions Our study highlights that AS-IV exerts a protective effect on the integrality of the mucosal barrier in UC based on the PI3K/AKT pathway, and AS-IV may serve as a novel AKT inhibitor to provide a potential therapy for UC. Graphical abstract

Abstract Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Abstract Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Abstract Background Video-assisted laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. While robotic surgery offering some specific advantages such as better three-dimensional (3D) stereoscopic vision, hand-eye consistency, and flexibility and stability with the endowrist is expected to be shorter in learning curve than that of LHM for surgeons who are proficient in LHM. The aim of this study was to describe a single surgeon’s experience related to the transition from video-assisted laparoscopic to robotic Heller myotomy with Dor fundoplication. Methods We conducted a retrospective observational study based on the recorded data of the first 66 Heller myotomy performed with laparoscopic Heller myotomy with Dor fundoplication (LHMD, 26 cases) and with the robotic Heller myotomy with Dor fundoplication (RHMD, 40 cases) by the same surgeon in Department of Thoracic Surgery of The First Affiliated Hospital of Nanchang University in China. The operation time and intraoperative blood loss were analyzed using the cumulative sum (CUSUM) method. Corresponding statistical tests were used to compare outcomes of both serials of cases. Results The median operation time was shorter in the RHMD group compared to the LHMD group (130 [IQR 123–141] minutes vs. 163 [IQR 153–169]) minutes, p

In recent years, intensive tunnel construction has induced a large number of karst collapses in the Gele Mountain area. However, the distribution, scale, cause and evolution of karst collapses have not been systematically summarized. By means of data collation, drilling data analysis, monitoring data interpretation and other working methods, this study systematically analyzes the development law and formation conditions of karst collapse in the Gelle Mountain region, conducts in-depth discussion of the cave-causing mechanism and evolution process, and comes to the following conclusions. Multiple groups of karst collapse are developed in the wide karst depression, trough or dense area of tectonic fissure covered by Quaternary silty clay in the tunnel site. The multi-stage rock cave and fracture system provide a good spatial development condition for the formation of karst collapse, and the cave-inducing force mainly comes from the change of groundwater dynamic condition caused by tunnel construction. The main mechanism of karst collapse is that tunnel construction changes the local groundwater environment, and the collapse of collapsible geological structures is induced by multi-effect caving in the reconstruction process. The development and evolution of karst collapse includes three stages: incubation, formation and stability. In the incubation period the water-rich karst fissure and cave system are initially exposed during tunnel construction. Space for soil migration and collapse is formed in the surface fissure and cave zone, and the local deformation and fall of overburden occur. In the formation period water diversion and discharge measures are usually adopted in tunnel construction and operation, and karst collapse is eventually formed under the action of multi-effect collapse. In the stable period, after tunnel operation to a certain stage, groundwater environment gradually tends to a new dynamic equilibrium, the existing karst collapse gradually becomes stable, collapse group no longer expands outward. The results can be used as reference for karst collapse monitoring and warning, ecological restoration and tunnel planning.

Abstract The application of the security region methodology in a practical distribution system with large scale normally requires large computer memory and high computation time. To overcome this problem, this article proposes a decoupling and dimension reduction method, which can significantly accelerate the calculation of distribution system security region (DSSR) and is important for the application of the DSSR theory in large‐scale distribution systems. First, the definition of DSSR dimension reflecting the size of solution space and the time complexity is proposed. And the solution algorithm for DSSR dimension is also given. Second, a decoupling and dimension reduction method suitable for the analysis of DSSR is proposed. Following the method, an incidence matrix can be obtained from the DSSR expressions, which can be further divided into multiple block matrices. According to the feeder combinations of the block matrices, the distribution system can be decoupled into multiple sub‐networks for more efficient analysis. Finally, a 10kV distribution network is used in case study to validate the proposed method. The results for a time‐consuming calculation, that is, TSC curve calculation, show that the proposed method can reduce the computation time significantly, making the time‐consuming calculation suitable for the analysis of large‐scale cases.

Abstract Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029–1.219) and weighted median (OR = 1.112, 95% CI 1.000–1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025–1.248) and weighted median (OR = 1.151, 95% CI 1.020–1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996–1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.

Summary: Background: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored. Methods: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments. Findings: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1high CD25high CD62Llow CD127low) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor. Interpretation: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications. Funding: Found in acknowledgements.

Abstract Over the tropical Indo‐Pacific, we explore the variations of Solar‐Induced Fluorescence (SIF), CO2, and precipitation during El Niño Southern Oscillation (ENSO) events verse other times. Based on various data sets, we analyze the time series of deseasonalized precipitation, vertical velocity, SIF, and CO2 across the Indo‐Pacific region. Our analysis reveals that there is less precipitation, more sinking air, lower SIF, and higher carbon dioxide over the Indo‐Pacific region during the El Niño events compared to other times. We also explore the spatial patterns of different variables to gain a deeper understanding of their relationships. The spatial analysis suggests that less precipitation resulting from predominant sinking air not only leads to lower SIF values by reducing photosynthetic activities but also triggers more biomass burning, which contribute to an increase in atmospheric CO2 levels across most areas of the Indo‐Pacific region. The comparative study between observational analyses and numerical simulation by the NOAA CarbonTracker model indicates that the model can simulate the increase of atmospheric column CO2 during the El Niño event, although there are some difficulties in capturing the correct spatial pattern. The results of this study can significantly enhance our understanding of the spatial‐temporal variabilities of atmospheric CO2 concentration and the observational characteristics can be used to enhance models. Furthermore, the complex interactions between ENSO and other variables revealed in this study improve our understanding of how ENSO influences the biosphere and carbon cycle.

Abstract Background The growth of rice is reduced by the slow decomposition of accumulated straw, which competes with rice for soil nitrogen nutrient. In recent year, straw-decomposing inoculants (SDIs) that can accelerate straw decomposition and ammonium nitrogen (N) fertilizer that can quickly generate available N is increasingly adopted in China. However, it is still unknown whether the N demand of straw decomposition and crop growth can be simultaneously met through the co-application of SDIs and ammonium N fertilizer. Results In this study, we investigated the effect of the co-application of SDIs and ammonium bicarbonate on decomposition rate of wheat straw, rice growth and rice yield over two consecutive years in rice-wheat rotation system. Compound fertilizer (A0) was used as control. The ratios of ammonium bicarbonate addition were 20% (A2), 30% (A3) and 40% (A4), respectively, without SDIs or with SDIs (IA2, IA3, IA4). Our results revealed that without SDIs, compared with A0, straw decomposition rate, rice growth and yield were improved under A2; However, under A3, rice yield was decreased due to the slow decomposition rate of straw and limited growth of rice during late growth stage. Combining SDIs and N fertilizer increased straw decomposition rate, rice growth rate and yield more than that of N fertilizer alone, especially under IA3. Compared with A0, straw decomposition rate, tiller number, aboveground biomass, leaf area index, root length, and nitrogen use efficiency were significantly increased by 16%, 8%, 27%, 12%, 17%, and 15% under IA3. Consequently, the average rice yield of IA3 was increased to 10,856 kg/ha, which was 13% and 9% higher, respectively, than of A0 and A2. Conclusion Our results indicated that ammonium bicarbonate application alone carried a risk of nutrient deficiency during late growth stage and yield decline. Therefore, the co-application of SDIs and 30% ammonium N fertilizer substitution can be a favorable practice to simultaneously accelerate straw decomposition and increase rice crop growth.

The central nervous system (CNS) is the most complex system in human body, and there is often a lack of effective treatment strategies for the disorders related with CNS. Natural compounds with multiple pharmacological activities may offer better options because they have broad cellular targets and potentially produce synergic and integrative effects. Bryostatin-1 is one of such promising compounds, a macrolide separated from marine invertebrates. Bryostatin-1 has been shown to produce various biological activities through binding with protein kinase C (PKC). In this review, we mainly summarize the pharmacological effects of bryostatin-1 in the treatment of multiple neurological diseases in preclinical studies and clinical trials. Bryostatin-1 is shown to have great therapeutic potential for Alzheimer’s disease, multiple sclerosis, fragile X syndrome, stroke, traumatic brain injury, and depression. It exhibits significant rescuing effects on the deficits of spatial learning, cognitive function, memory and other neurological functions caused by diseases, producing good neuroprotective effects. The promising neuropharmacological activities of bryostatin-1 suggest that it is a potential candidate for the treatment of related neurological disorders although there are still some issues needed to be addressed before its application in clinic.

Abstract Mid‐tropospheric Carbonyl sulfide (OCS) retrievals from the Tropospheric Emission Spectrometer (TES) are utilized to study OCS distributions during the dry/wet seasons over the Amazon rainforest. TES OCS retrievals reveal positive OCS anomalies (∼16 ppt) over the central and southern parts of the Amazon during August–October (dry season) compared to January–March (wet season). There is less OCS taken up by vegetation and soil and more OCS released from biomass burning during the dry season, which causes an increase in OCS concentrations. Strong sinking air during the dry season also helps to trap OCS and this contributes to positive OCS anomalies. MOZART‐4 model captures positive OCS anomalies over the central and southern regions of the Amazon and negative OCS anomalies over the northern part of the Amazon, which are similar to those from TES mid‐tropospheric OCS retrievals. Our studies can help us better understand OCS variations and photosynthetic activities.

BackgroundResearch on asthma control levels and quality of life is essential for children with asthma during their growth stage. Therefore, it is necessary to develop a questionnaire that can be used for monitoring and evaluating the disease control effectiveness and quality of life of children with asthma in China and to conduct a preliminary evaluation for its reliability, validity, and discriminative ability.MethodsThe questionnaire was created through a literature review and qualitative interviews for a targeted population. Based on the previous work, 30 caregivers of children with asthma and 5 experienced pediatricians reviewed and discussed a collection of items. Then, 72 items were screened and selected to form the draft questionnaire. After three rounds of investigation (with 240, 503, and 360 participants, respectively), the final questionnaire was established according to the evaluation results. The structure of the questionnaire was explored through confirmatory factor analysis. Exploratory factor analysis and variability analysis were applied based on the first two rounds of investigation. Reliability, construct validity, and discriminative ability were evaluated based on the third round of investigation.ResultsThe questionnaire contains 6 dimensions and 34 items, and the total cumulative variance contribution rate was 54.96%; Cronbach's α coefficient was 0.91; the split-half reliability coefficient was 0.75, and the test–retest reliability coefficient was 0.74. The children's age, gender, residence, asthma attack in the last three months, caregivers' education background, and monthly income per caregiver were correlated with patient-reported outcomes of children with asthma.ConclusionThe questionnaire appeared to have good reliability, construct validity, and discriminative ability in children with asthma in China.

Clinical cancer trials are designed to collect radiographic measurements of each patient’s baseline and residual tumor burden at regular intervals over the course of study. For solid tumors, the extent of reduction in tumor size following treatment is used as a measure of a drug’s antitumor activity. Statistical estimation of treatment efficacy routinely reduce the longitudinal assessment of tumor burden to a binary outcome describing the presence versus absence of an objective tumor response as defined by RECIST criteria. The objective response rate (ORR) is the predominate method for evaluating an experimental therapy in a single-arm trial. Additionally, ORR is routinely compared against a control therapy in phase III randomized controlled trials. The longitudinal assessments of tumor burden are seldom integrated into a formal statistical model, nor integrated into mediation analysis to characterize the relationships among treatment, residual tumor burden, and survival. This article presents a frameworkfor landmark mediation survival analyses devised to incorporate longitudinal assessment of tumor burden. R2 effect-size measures are developed to quantify the survival treatment mediation effects using longitudinal predictors. Analyses are demonstrated with applications to two colorectal cancer trials. Survival prediction is compared in the presence versus absence of longitudinal analysis. Simulation studies elucidate settings wherein patterns of tumor burden dynamics require longitudinal analysis.

Abstract Background The objective of this study was to develop a scale to assess eating behaviors of school-aged children (6–12 years old) in China. Methods To develop the scale, a literature review and qualitative interviews were conducted. The draft scale contained 115 items and went through three evaluations among three groups of caregivers (n = 140, 400, 700) selected from suburban and urban kindergartens in Xi’an, Hanzhong, and Yanan, China, from March 2017 to October 2018. The psychometric properties of the scale were assessed using exploratory, confirmatory factor analysis, and variability analysis. Results The final scale consisted of 46 items across eight dimensions including food fussiness, satiety responsiveness, food responsiveness, bad eating habits, susceptible diet, restrained eating, enjoyment of food, and junk food addiction. The total cumulative variance contribution rate was 52.16%. The scale and dimensions' Cronbach’s α coefficients, Guttman split-half reliability, and test- retest reliability were all above 0.65. The fitting indices for the confirmatory factor analysis were all close to 1. The scores for education of caregiver, family structure, and the body mass index of children were different among dimensions and groups, thus suggesting good discriminative utility. Conclusions All of the results indicated that the scale has good reliability and construct validity for evaluating the eating behaviors of school-aged children in China.

Pulmonary hemorrhage (PH) is a rare acute catastrophic event with high mortality among neonates, especially preterm infants. Primary treatments included pulmonary surfactant, high-frequency oscillatory ventilation, epinephrine, coagulopathy management, and intermittent positive pressure ventilation. However, there are still challenges in diagnosing and treating refractory or focal pulmonary hemorrhages. Ultra-slim bronchoscopy has been widely used in the field of critically ill children and is increasingly being done in neonates with critical respiratory disease in recent years. In this study, we report a case with refractory pulmonary hemorrhage in premature infants, which was finally diagnosed as localized hemorrhage in the upper left lobe and cured by ultra-slim bronchoscopy-guided topical hemostatic drug administration. Bronchoscopy is an optional, safe, and practicable technique for early diagnosis and direct injection therapy of neonatal PH in managing life-threatening PH.

T-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical studies. As IL-15 has been shown to strengthen the anti-tumor response, we have modified CD4 CAR to secrete an IL-15/IL-15sushi complex. These CD4-IL15/IL15sushi CAR T cells and NK92 cells efficiently eliminated CD4+ leukemic cell lines in co-culture assays. Additionally, CD4-IL15/IL15sushi CAR out-performed CD4 CAR in in vivo models, demonstrating a benefit to IL-15/IL-15sushi inclusion. In a Phase I clinical trial, CD4-IL15/IL15sushi CAR T cells were tested for safety in three patients with different T-cell lymphomas. Infusion of CD4-IL15/IL15sushi CAR T cells was well-tolerated by the patients without significant adverse effects and led to the remission of their lymphomas. Additionally, infusion led to the depletion of CD4+ Treg cells and expansion of CD3+CD8+ T cells and NK cells. These results suggest that CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are needed.

ObjectiveAs monotherapy is insufficient for some patients, the existing fixed-dose combination (FDC) requires two or more daily administrations with declining adherence. The present study compared the efficacy and safety of netarsudil/latanoprost FDC with monotherapy of its individual components in patients with glaucoma.MethodsA systematic literature search was performed for studies comparing netarsudil/latanoprost fixed-dose combination (FDC) vs. monotherapy in patients with glaucoma. The primary endpoints included intraocular pressure (IOP), intraocular pressure reduction percentage (IOPR%) and adverse events (AEs).ResultsThree randomized controlled trial studies (RCTs) involving 1,692 patients (FDC: 556, netarsudil: 577, latanoprost: 559) were included in this meta-analysis. FDC was more effective than netarsudil, with significantly lower diurnal IOP over three time points (8:00 a.m., 10:00 a.m., 4:00 p.m.), mean diurnal IOP (MD = −2.36 [−3.08, −1.63], P < 0.00001) and higher IOPR% (MD = 9.60 [7.86, 11.33], P < 0.00001). When comparing FDC with latanoprost, both mean diurnal IOP (MD = −1.64 [−2.05, −1.23], P < 0.00001) and diurnal IOP across 3 time points were significantly lower with FDC than with latanoprost, while FDC induced significantly higher IOPR% (MD = 6.09 [4.40, 7.77], P < 0.00001). Incidence of total AEs was similar between netarsudil and FDC, but higher with FDC than with latanoprost.ConclusionNetarsudil/latanoprost FDC appears to be superior to netarsudil or latanoprost alone, with better ocular hypotensive effects. However, there are concerns that netarsudil/latanoprost FDC was associated with a significantly higher incidence of AEs specifically compared with latanoprost.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311956.

Abstract Functional gastrointestinal disorders (FGIDs) are common among the aircrew due to their arduous working environment. This study investigated the prevalence of FGIDs in Chinese male pilots and assessed the effects of trigger factors on the FGIDs. A cross-sectional study including 212 male pilots was performed in a Chinese large civil airline company. FGIDs were diagnosed according to the Rome IV diagnostic criteria. The psychological performance, dietary pattern, sleep situation, and physical activity of the respondents were assessed. Logistic regression analysis and structural equation modeling were used to explore the association between these trigger factors and FGIDs. FGIDs were observed in 83 (39.22%) respondents, of which 31 (37.35%) had overlap syndromes. Age, flight level, flight time, high-salt food pattern, anxiety, and sleep performance were found to be associated with FGIDs (all P

Abstract Background The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). Methods We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. Results In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P

Background: Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid (SXOL), have been recommended to alleviate dyspeptic symptoms. However, evidence of their safety and efficacy remains limited to date. AIM: To assess whether 2 weeks of therapy with SXOL was non-inferior to domperidone syrup in children with FD.Methods: In this randomized, double-blind, double-simulated, non-inferiority, multi-center clinical trial, we recruited children (3–14 years) with FD according to the Rome IV criteria from 17 tertiary medical centers across China. Patients were randomly allocated (1:1) to receive SXOL or domperidone syrup for 2 weeks. We compared the participants’ clinical scores from both groups based on the severity and frequency of dyspepsia symptoms according to Rome IV criteria (0, 1, 2, and 4 weeks after randomization). The primary endpoint was the total response rate, which was defined as the proportion of patients with a decrease of 30% or more in the FD symptoms clinical score from baseline, at the end of the 2-weeks treatment. A non-inferiority margin of -10% was set. Secondary endpoints and adverse events were assessed. This trial is registered with www.Chictr.org.cn, number ChiCTR1900022654.Results: Between February 2019 and March 2021, a total of 373 patients were assessed for eligibility, and 356 patients were enrolled and randomized. The clinical response rate at week two was similar for SXOL [118 (83.10%) of 142] and domperidone [128 (81.01%) of 158]; difference 2.09; 95% CI −6.74 to 10.71, thereby establishing non-inferiority. The total FD symptom scores were significantly improved in the two groups at 1-, 2-, and 4-weeks follow-up periods (p < 0.005). The decrease in symptom score compared with the baseline were similar between these two groups. Over the total study period, 10 patients experienced at least one treatment-related adverse event [six (3.37%)] in the SXOL group, four [(2.25%) in the domperidone group], although no serious adverse event was noted.Conclusion: Treatment with SXOL effectively improves dyspeptic symptoms and is well tolerated. In addition, it is not inferior to domperidone syrup and leads to sustained improvement in Chinese children with FD.

Objective. To investigate the efficacy of subhypothermia in the treatment of neonatal hypoxic-ischemic encephalopathy (HIE) combined with myocardial damage. Methods. 136 children with HIE and myocardial damage admitted to our hospital from October 2019 to October 2021 were included in the study and were divided into study group and control group of 68 cases each according to the random number table method. The control group was given conventional treatment, and the study group was treated with subhypothermia therapy on top of the control group. Comparing the effects of treatment between the two groups. The serum levels of S-100β protein, Tau protein, neuron-specific enolase (NSE), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (ɑ-HBDH), myoglobin (Myo), cardiac trophic factor-1 (CT-1), cardiac troponin I (cTnI), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), interleukin-1β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-ɑ (TNF-ɑ) were measured in both groups before and after treatment, respectively. Results. The total effective rate was higher in the study group (88.24%) than in the control group (72.06%) (P

Abstract Previous studies suggested that the Amazon, the largest rainforest on Earth, changes from a CO2 sink to a CO2 source during the dry/fire season. However, the biospheric contributions to atmospheric CO2 are not well understood during the two main seasons, the dry/fire season and the wet season. In this article, we utilize Orbiting Carbon Observatory 2 (OCO‐2) Solar‐Induced Fluorescence (SIF) to explore photosynthetic activity during the different seasons. The spatiotemporal variability of OCO‐2 SIF, OCO‐2 CO2, precipitation, and burned area are investigated over the Amazon from September 2014 to December 2019. Averaging over the entire Amazon region, we found a positive temporal correlation (0.94) between OCO‐2 SIF and Global Precipitation Climatology Project precipitation and a negative temporal correlation (−0.64) between OCO‐2 SIF and OCO‐2 CO2, consistent with the fact that precipitation enhances photosynthesis, which results in higher values for SIF and rate of removal of CO2 from the atmosphere above the Amazon region. We also observed seasonality in the spatial variability of these variables within the Amazon region. During the dry/fire (August–October) season, low SIF values, low precipitation, high vapor pressure deficit (VPD), large burned areas, and high atmospheric CO2 are mainly found over the southern Amazon region. In contrast, during the wet season (January–March), high SIF values, high precipitation, low VPD, smaller burned areas, and low CO2 are found over both the central and southern Amazon regions. The seasonal difference in SIF suggests that photosynthetic activity is reduced during the dry/fire season relative to the wet season as a result of low precipitation and high VPD, especially over the southern Amazon region, which will contribute to more CO2 in the atmosphere during the dry/fire season.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.

Abstract The interannual variability of tropical carbon monoxide from the Microwave Limb Sounder over 2004–2018 period is dominated by the quasi‐biennial oscillation (QBO). We simulate the carbon monoxide variability over this period using the 2‐D Caltech/JPL chemistry‐transport model. The chemistry‐transport model includes the photochemical sources and sinks and transport driven by a stream function and eddy diffusivity derived from the assimilated winds of National Centers for Environmental Prediction Reanalysis 2. The results show good agreement between model and Microwave Limb Sounder observations. We also investigate the anomalous period 2015–2016, when the QBO winds deviated significantly from their climatological values. The model simulations could capture the QBO features in agreement with observations for the anomalous period.

Abstract Background Congenital chloride diarrhea (CCD) in a newborn is a rare autosomal recessive disorder with life-threatening complications, requiring early diagnostics and treatment to prevent severe dehydration and infant mortality. SLC26A3 rs386833481 (c.392C>G; p.P131R) gene polymorphism is an important genetic determinant of CCD. Here, we report the influence of the non-synonymous SLC26A3 variant rs386833481 gene polymorphism on the function of the epithelial barrier and the potential mechanisms of these effects. Results We found that P131R-SLC26A3 increased dysfunction of the epithelial barrier compared with wild type SLC26A3 in human colonic Caco-2 and mouse colonic CMT-93 cells. When P131R-SLC26A3 was subsequently reverted to wild type, the epithelial barrier function was restored similar to wild type cells. Further study demonstrated that variant P131R-SLC26A3 disrupts function of epithelial barrier through two distinct molecular mechanisms: (a) decreasing SLC26A3 expression through a ubiquitination pathway and (b) disrupting a key interaction with its partner ZO-1/CFTR, thereby increasing the epithelial permeability. Conclusion Our study provides an important insight of SLC26A3 SNPs in the regulation of the epithelial permeability and indicates that SLC26A3 rs386833481 is likely a causative mutation in the dysfunction of epithelial barrier of CCD, and correction of this SNP or increasing SLC26A3 function could be therapeutically beneficial for chronic diarrhea diseases.

Cigar tobacco is an important economic crop that is widely grown around the world. In recent years, varietal identification has become a frequent problem in germplasm preservation collections, which causes considerable inconvenience and uncertainty in the cataloging and preservation of cigar germplasm resources, in the selection of parental lines for breeding, and in the promotion and use of high quality varieties. Therefore, the use of DNA fingerprints to achieve rapid and accurate identification of varieties can play an important role in germplasm identification and property rights disputes. In this study, we used genotyping-by-sequencing (GBS) on 113 cigar tobacco accessions to develop SNP markers. After filtering, 580,942 high-quality SNPs were obtained. We used the 580,942 SNPs to perform principal component analysis (PCA), population structure analysis, and neighbor joining (NJ) cluster analysis on the 113 cigar tobacco accessions. The results showed that the accessions were not completely classified based on their geographical origins, and the genetic backgrounds of these cigar resources are complex and diverse. We further selected from these high-quality SNPs to obtained 163 SNP sites, 133 of which were successfully converted into KASP markers. Finally, 47 core KASP markers and 24 candidate core markers were developed. Using the core markers, we performed variety identification and fingerprinting in 216 cigar germplasm accessions. The results of SNP fingerprinting, 2D barcoding, and genetic analysis of cigar tobacco germplasm in this study provide a scientific basis for screening and identifying high-quality cigar tobacco germplasm, mining important genes, and broadening the basis of cigar tobacco genetics and subsequent breeding work at the molecular level.

Objective: To evaluate the health-related quality of life (HRQoL) status and explore its associated factors in pediatric medical staff during the COVID-19 epidemic so as to provide fundamental evidence for clinicians and administrators to formulate targeted intervention measures to improve the HRQoL and mental health status in pediatric medical staff during this, and future pandemics.Methods: A cross-sectional study was conducted to investigate the HRQoL of pediatric medical staff. Univariable and multivariable logistic regression were used to analyze the associated factors.Results: A total of 2,997 participants were recruited. Females scored worse than males in terms of emotional functioning (OR = 1.6, 95% CI: 1.2–2.1) and cognitive functioning (OR = 1.4, 95% CI: 1.1–1.8). The respondents aged 30–39 and 40–49 years scored worse in nearly all domains of HRQoL compared health care professionals under 30 years old. Respondents with high education had lower scores in physical functioning (OR = 1.3, 95% CI: 1.0–1.7) and emotional functioning (OR = 1.5, 95% CI: 1.2–1.9). Compared with doctors, nurses had higher scores in all domains except for summary score and worry. The respondents whose working places had not set up pediatric fever clinics and isolated observation areas independently had lower scores in all domains except for worry. The respondents who had ever treated patients with COVID-19 had lower scores in all domains.Conclusion: During the COVID-19 outbreak, the HRQoL of pediatric medical staff decreased. The factors associated with HRQoL can be used to develop intervention to improve HRQoL in pediatric medical staff.

The long-term Lorenz energy cycle of Earth’s global remains poorly explored. Here, the authors use three independent meteorological data sets from the modern satellite era (1979–2013) to examine the temporal characteristics of such a cycle.

Pneumonia poses a significant global morbidity and mortality burden on children. Etiological diagnosis and matched anti-microbial therapy are particularly important for very severe pneumonia. Although great advances have been achieved in diagnostic approaches, it remains challenging to identify pathogens in unexplained pneumonia (UP) cases. In this study, we applied next-generation sequencing (NGS) technology and a metagenomic approach to detect and characterize respiratory bactiera in an UP case in infant. Stenotrophomonas maltophilia was the only bacterial pathogen detected in blood. Metagenomic sequencing also provided bacteria genomic sequences, which could be used to evaluate the role of this pathogen in the disease. This NGS method has the potential to improve the identification of causative organisms in patients with pneumonia and the delivery of appropriate, pathogen-directed antibiotic therapy.

Hirschsprung disease (HSCR) is a common developmental disorder of the enteric nervous system (ENS). However, the disease mechanisms have not been fully elucidated. To better understand the etiology of HSCR, the role and mechanism of HSCR associated PTPRR (protein tyrosine phosphatase receptor-type R) in the multipotency of ENS progenitors and ENS development were explored. In the present study, the downregulated PTPRR expression in HSCR was reflected by microarray and validated by real-time PCR analyses. Moreover, PTPRR protein was mainly expressed in the cytoplasmic area of primary cultured ENS progenitors (Enteric neural crest cells, ENCCs) and significantly decreased after differentiation induction, which implies the anti-differentiation role in ENCCs. Further study employed an adenovirus transfection system. After genetic modulation, the ENCCs maintained undifferentiated patterns even in GDNF (Glial cell-line derived neurotrophic factor)-mediated directional differentiation, as well as significantly increased EdU positive immunofluorescence in the PTPRR overexpressing group while the development of the ENS was stunted in the PTPRR knockdown fetal gut. Moreover, the expression of ERK1/2 activated by GDNF was significantly decreased as reflected by western-blot or immunofluorescence analyses after genetic modulation in the PTPRR overexpressing group, which suggests the potential mechanism in regulating the MAPK/ERK1/2 pathway. Taken together, These data support the idea that PTPRR may ensure a certain number of neural precursor cells by inhibiting ENCC overt differentiation and maintaining ENCC proliferation, which is considered to be the multipotency of ENCCs, and eventually participate in the development of the ENS, and establish PTPRR protein as negative regulator of MAPK/ERK1/2 signaling cascades in neuronal differentiation and demonstrate their involvement in the pathophysiology of HSCR.

Type VI protein secretion systems (T6SSs) have been identified in many plant-associated bacteria. However, despite the fact that effector proteins may modulate host responses or interbacterial competition, only a few have been functionally dissected in detail. We dissected the T6SS in Azoarcus olearius strain BH72, a nitrogen-fixing model endophyte of grasses. The genome harbors two gene clusters encoding putative T6SSs, tss-1 and tss-2, of which only T6SS-2 shared genetic organization and functional homology with the H1-T6SS of Pseudomonas aeruginosa. While tss-2 genes were constitutively expressed, tss-1 genes were strongly up-regulated under conditions of nitrogen fixation. A comparative analysis of the wild type and mutants lacking either functional tss-1 or tss-2 allowed to differentiate the functions of both secretion systems. Abundance of Hcp in the culture supernatant as an indication for T6SS activity revealed that only T6SS-2 was active, either under aerobic or nitrogen-fixing conditions. Our data show that T6SS-2 but not T6SS-1 is post-translationally regulated by phosphorylation mediated by TagE/TagG (PpkA/PppA), and by the phosphorylation-independent inhibitory protein TagF, similar to published work in Pseudomonas. Therefore, T6SS-1 appears to be post-translationally regulated by yet unknown mechanisms. Thus, both T6SS systems appear to perform different functions in Azoarcus, one of them specifically adapted to the nitrogen-fixing lifestyle.

The Notch pathway plays critical roles in the development and functional modulation of myeloid cells. Previous studies have demonstrated that Notch activation promotes M1 polarization and phagocytosis of macrophages; however, the downstream molecular mechanisms mediating Notch signal remain elusive. In an attempt to identify Notch downstream targets in bone marrow-derived macrophages (BMDMs) using mass spectrometry, the signal regulatory protein α (SIRPα) appeared to respond to knockout of recombination signal-binding protein Jk (RBP-J), the critical transcription factor of Notch pathway, in macrophages. In this study, we validated that Notch activation could repress SIRPα expression likely via the Hes family co-repressors. SIRPα promoted macrophage M2 polarization, which was dependent on the interaction with CD47 and mediated by intracellular signaling through SHP-1. We provided evidence that Notch signal regulated macrophage polarization at least partially through SIRPα. Interestingly, Notch signal regulated macrophage phagocytosis of tumor cells through SIRPα but in a SHP-1-independent way. To access the translational value of our findings, we expressed the extracellular domains of the mouse SIRPα (mSIRPαext) to block the interaction between CD47 and SIRPα. We demonstrated that the soluble mSIRPαext polypeptides could promote M1 polarization and increase phagocytosis of tumor cells by macrophages. Taken together, our results provided new insights into the molecular mechanisms of notch-mediated macrophage polarization and further validated SIRPα as a target for tumor therapy through modulating macrophage polarization and phagocytosis.