In silico analysis of the wild-type and mutant-type of BRCA2 gene.

BACKGROUND: The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure-function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). METHODS: A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient's whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein-protein docking (HADDOCK) algorithm and protein-ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. RESULTS: Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. CONCLUSION: Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

The different responses of AOA and AOB communities to irrigation systems in the semi-arid region of Northeast China.

Ammonia oxidation is the rate-limiting step in nitrification and the key step in the nitrogen (N) cycle. Most soil nutrients and biological indicators are extremely sensitive to irrigation systems, from the perspective of improving soil fertility and soil ecological environment, the evaluation of different irrigation systems and suitability of selection, promote crop production and soil quality, study the influence of the soil microenvironment contribute to accurate evaluation of irrigation farmland soil health. Based on the amoA gene, the abundance and community diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) and their responses to soil physicochemical factors and enzyme activities were studied in semi-arid areas of Northeast China. The study consisted of three irrigation systems: flood irrigation (FP), shallow buried drip irrigation (DI), and mulched drip irrigation (MF). The results showed that DI and MF significantly increased the contents of alkaline hydrolyzed nitrogen (AN), nitrate nitrogen (NO3--N), soil moisture, and the activities of ammonia monooxygenase (AMO) and hydroxylamine oxidase (HAO). Compared with FP, DI significantly increased the abundance of soil AOA and AOB, while MF significantly increased the abundance of soil AOB. Irrigation systems significantly affected the community composition of ammonia-oxidizing microorganisms (AOM). Also, AN and soil moisture had the greatest influence on the community composition of AOA and AOB, respectively. The AOB community had better stability and stress resistance. Moreover, the symbiotic network of AOB in the three irrigation systems was more complex than that of AOA. Compared with FP, the AOA community under treatment DI had higher complexity and stability, maintaining the versatility and sustainability of the ecosystem, while the AOB community under treatment MF had higher transfer efficiency in terms of matter and energy. In conclusion, DI and MF were more conducive to the propagation of soil AOM in the semi-arid area of Northeast China, which can provide a scientific basis for rational irrigation and N regulation from the perspective of microbiology.

Light-Sheet Microscopic Imaging of Whole-Mouse Vascular Network with Fluorescent Microsphere Perfusion.

Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 µm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.

Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Patient perceptions and preferences of minimally invasive treatment modalities in varicose veins: a cross-sectional survey.

Purpose: Minimally invasive therapies (MIT) have gained popularity due to their capacity to reduce trauma, enhance aesthetic outcomes, and shorten recovery periods. This article explores patients' perceptions and preferences regarding MIT for varicose veins (VVs) while analyzing associated influencing factors to provide a better understanding. Patients and methods: A cross-sectional survey at Zhejiang Rongjun Hospital was performed from January 2022 to June 2023, involving 305 participants with VVs. The questionnaire assessed patient demographics, VVs severity, prior treatment experiences, and treatment preferences. Statistical analyses, including chi-square and Kruskal-Wallis tests, were conducted to explore the correlations between patient characteristics, treatment preferences, and factors influencing these choices. Results: Nearly half of the participants (44.3%) lacked information on any surgical options, whereas a slight majority (55.7%) possessed familiarity with at least one treatment modality, and only 9.8% knew of all six treatment methods presented. Patient surveys discerned that the majority (68.5%) declared an inadequate grasp of treatment methodologies to articulate a treatment preference. Among the 96 patients who made a treatment choice, 24.0% opted for traditional surgery, while 76.0% chose MIT and a higher preference for MIT among male patients compared to female patients (p = 0.006). The patients preferred treatment options for VVs significantly affected by vascular surgeon recommendations and the number of follow-up visits (r = 0.129, p = 0.024; r = 0.122, p = 0.033). Conclusion: The study highlights limited awareness of MIT among Chinese patients with VVs. The insights emphasize the influential role of vascular surgeons' recommendations and suggest a growing predilection for less invasive treatments due to their advantages in recovery and aesthetics. Provider-patient communication, including education about available treatments and shared decision-making, is essential to align treatment plans with patient expectations and improve outcomes.

Intervention of exogenous VEGF protect brain microvascular endothelial cells from hypoxia-induced injury by regulating PLCγ/RAS/ERK and PI3K/AKT pathways.

Ischemic stroke rapidly increases the expression level of vascular endothelial growth factor (VEGF), which promotes neovascularization during hypoxia. However, the effect and mechanism of VEGF intervention on cerebrovascular formation remain unclear. Therefore, our research discussed the protective effect of exogenous VEGF on cells in hypoxia environment in cerebral microvascular endothelial cells, simulating ischemic stroke in hypoxic environment. Firstly, we detected the proliferation and apoptosis of cerebral microvascular endothelial cells under hypoxia environment, as well the expression levels of VEGF-E, vascular endothelial growth factor re-ceptor-2 (VEGFR-2), BCL2, PRKCE and PINK1. Moreover, immunofluorescence and western blotting were used to verify the regulation of exogenous VEGF-E on VEGFR-2 expression in hypoxic or normal oxygen environment. Lastly, we manipulated the concentration of VEGF-E in the culture medium to investigate its impact on phospholipase Cγ1 (PLCγ1)/extracellular signaling regulatory protein kinase (ERK) -1/2 and protein kinase B (AKT) pathways. Additionally, we employed a PLCγ1 inhibitor (U73122) to investigate its impact on proliferation and PLCγ1/ERK pathways. The results show that hypoxia inhibited the proliferation of cerebral microvascular endothelial cells, promoted cell apoptosis, significantly up-regulated the expression of VEGF-E, VEGFR-2, PRKCE and PINK1, but down-regulated the expression of BCL2. Interference from exogenous VEGF-E activated PLCγ1/ERK-1/2 and AKT pathways, promoting cell proliferation and inhibiting apoptosis of hypoxic brain microvascular endothelial cells. In summary, exogenous VEGF-E prevents hypoxia-induced damage to cerebral microvascular endothelial cells by activating the PLCγ1/ERK and AKT pathways. This action inhibits the apoptosis pathway in hypoxic cerebral microvascular endothelial cells, thereby safeguarding the blood-brain barrier and the nervous system.

Itaconate protects ferroptotic neurons by alkylating GPx4 post stroke.

Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.

Hybrid feature selection in a machine learning predictive model for perioperative myocardial injury in noncoronary cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Perioperative myocardial injury (PMI) is associated with increased mobility and mortality after noncoronary cardiac surgery. However, limited studies have developed a predictive model for PMI. Therefore, we used hybrid feature selection (FS) methods to establish a predictive model for PMI in noncoronary cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This was a single-center retrospective study conducted at the Fuwai Hospital in China. Patients aged 18-70 years who underwent elective noncoronary surgery with CPB at our institution from December 2018 to April 2021 were enrolled. The primary outcome was PMI, defined as the postoperative cardiac troponin I (cTnI) levels exceeding 220 times of upper reference limit (URL). Statistical analyses were conducted by Python (Python Software Foundation, version 3.9.7 and integrated development environment Jupyter Notebook 1.1.0) and SPSS software version 26.0 (IBM Corp., Armonk, New York, USA). RESULTS: A total of 1130 patients were eventually eligible for this study. The incidence of PMI was 20.3% (229/1130) in the overall patients, 20.6% (163/791) in the training dataset, and 19.5% (66/339) in the testing dataset. The logistic regression model performed the best AUC of 0.6893 (95 CI%: 0.6371-0.7382) by the traditional selection method, and the random forest model performed the best AUC of 0.6937 (95 CI%: 0.6416-0.7423) by the union of Wrapper and Embedded method, and the CatBoost model performed the best AUC of 0.6828 (95 CI%: 0.6304-0.7320) by the union of Embedded and forward logistic regression technique, and the Naïve Bayes model achieved the best AUC with 0.7254 (95 CI%: 0.6746-0.7723) by forwarding logistic regression method. Moreover, the decision tree, KNeighborsClassifier, and support vector machine models performed the worse AUC in all selection forms. Furthermore, the SHapley Additive exPlanations plot showed that prolonged CPB, aortic clamp time, and preoperative low platelets count were strongly related to the PMI risk. CONCLUSIONS: In total, four category feature selection methods were utilized, comprising five individual selection techniques and 15 combined methods. Notably, the combination of logistic regression and embedded methods demonstrated outstanding performance in predicting PMI risk. We also concluded that the machine learning model, including random forest, catboost, and Naive Bayes, were suitable candidates for establishing PMI predictive model. Nevertheless, additional investigation and validation are imperative for substantiating these finding.

Mass Spectrometry-Based Proteomics Analysis Unveils PTPRS Inhibits Proliferation and Inflammatory Response of Keratinocytes in Psoriasis.

In this study, we used data-independent acquisition-mass spectrometry (DIA-MS) to analyze the serum proteome in psoriasis vulgaris (PsO). The serum proteomes of seven healthy controls and eight patients with PsO were analyzed using DIA-MS. Weighted gene co-expression network analysis was used to identify differentially expressed proteins (DEPs) that were closely related to PsO. Hub proteins of PsO were also identified. The Proteomics Drug Atlas 2023 was used to predict candidate hub protein drugs. To confirm the expression of the candidate factor, protein tyrosine phosphatase receptor S (PTPRS), in psoriatic lesions and the psoriatic keratinocyte model, immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blotting were performed. A total of 129 DEPs were found to be closely related to PsO. The hub proteins for PsO were PVRL1, FGFR1, PTPRS, CDH2, CDH1, MCAM, and THY1. Five candidate hub protein drugs were identified: encorafenib, leupeptin, fedratinib, UNC 0631, and SCH 530348. PTPRS was identified as a common pharmacological target for these five drugs. PTPRS knockdown in keratinocytes promoted the proliferation and expression of IL-1α, IL-1ß, IL-23A, TNF-α, MMP9, CXCL8, and S100A9. PTPRS expression was decreased in PsO, and PTPRS negatively regulated PsO. PTPRS may be involved in PsO pathogenesis through the inhibition of keratinocyte proliferation and inflammatory responses and is a potential treatment target for PsO.

Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS: We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS: Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS: Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 µm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

Observation of dichotomic field-tunable electronic structure in twisted monolayer-bilayer graphene.

Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

Congenital chloride diarrhoea in a Chinese infant with a compound heterozygous SLC26A3 mutation.

INTRODUCTION: Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations. CASE PRESENTATION: A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency. CONCLUSIONS: CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

Investigation on the Nanopore Heterogeneity in Coals and its Influence on Methane Adsorption: A Multifractal Theory Study.

Coalbed methane (CBM) reservoirs constitute a distinct class of dense organic rocks characterized by extremely low porosity and permeability. Conducting an in-depth investigation into pore heterogeneity assumes paramount importance for the exploration and development of CBM. This study focuses on the multifractal analysis of the pores with diameters below 300 nm in six coal samples sourced from the Junggar Basin and the Qinshui Basin in China. The analysis is based on a series of experiments involving CO2 adsorption, low-temperature N2 adsorption/desorption, and CH4 isothermal adsorption. This work delves into the influence of pore heterogeneity on gas adsorption capacity by linking the structural parameters to CH4 adsorption properties. The results indicate that both the micropores, as assessed through CO2 adsorption, and mesopores to macropores, measured via N2 adsorption, exhibit multifractal behavior. In contrast to micropores, the mesopores and macropores display stronger heterogeneity and lower connectivity. Generally, uniform and well-connected nanopores are anticipated to positively contribute to gas adsorption. However, there is a positive correlation between the Langmuir volume and the heterogeneity degree of micropores. This phenomenon is ascribed to the fact that the greater surface complexity in micropores involves a larger specific surface area and a higher abundance of adsorption sites. This research contributes to a more profound and precise comprehension of the heterogeneous pore structure within CBM reservoirs, thereby establishing a theoretical foundation for the sustainable exploitation of CBM.

Effective treatment of corticosteroid-induced facial erythema using fractional radiofrequency microneedling.

OBJECTIVES: To investigate the efficacy of Fractional Radiofrequency Microneedling (FRM) in treating corticosteroid-induced facial erythema. METHODS: A retrospective study was conducted involving eight patients diagnosed as corticosteroid-induced facial erythema. Each patient underwent a single session of FRM. Evaluative measures included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), assessment of telangiectasia severity, procedure-associated pain (10-point scale), patient satisfaction (3-point scale) and secondary outcomes. RESULTS: The study found a 75% success rate and 100% effectiveness rate in alleviating erythema symptoms. CEA and PSA scores decreased by 67.7% and 78.1%, respectively. No cases of erythema rebound were recorded during the 3-month follow-up period. CONCLUSIONS: FRM demonstrated effectiveness and safety in treating facial erythema, offering promising advancement in dermatologic therapeutics.

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering.

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.