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Objective: Immune tolerance and evasion play a critical role in virus‐driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD‐1) and its ligands, PD‐L1 and PD‐L2, in aggressive acquired immunodeficiency syndrome (AIDS)‐related non‐Hodgkin lymphoma (AR‐NHL) remain poorly understood, particularly in the Epstein–Barr virus (EBV)‐positive subset. Methods: We used in situ hybridization with EBV‐encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD‐1/PD‐L1/L2 pathway in a multi‐institutional cohort of 58 patients with AR‐NHL and compared EBV‐positive and EBV‐negative cases. Results: The prevalence of EBV+ in AR‐NHL was 56.9% and was associated with a marked increase in the expression of PD‐1/PD‐L1/PD‐L2 in malignant cells. Patients with AR‐NHLs who tested positive for both EBER and PD‐1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD‐L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD‐1 tissue‐expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD‐1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD‐L1 (r = 0.354, p = 0.014) expression. Conclusions: These data emphasize the importance of PD‐1‐mediated immune evasion in the complex landscape of immune oncology in AR‐NHL co‐infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup. [ABSTRACT FROM AUTHOR]

(Pb,La)(Zr,Sn,Ti)O3‐based antiferroelectric ceramics have excellent energy storage performance(more than 90% efficiency), which make them have great application advantages in the field of ceramic capacitors. However, the sintering temperature of (Pb,La)(Zr,Sn,Ti)O3‐based antiferroelectric ceramics is generally above 1250 °C, which limits application as a material for ceramic capacitors. Cu inner electrode has a low co‐firing temperature and high conductivity and a low cost price, making it more competitive in the field of ceramic capacitor inner electrode. Therefore, the first step is to reduce the sintering temperature of (Pb,La)(Zr,Sn,Ti)O3‐based ceramics to below 1000 °C(co‐firing temperature with Cu inner electrode), which is the key and difficult point. In this paper, Pb0.94La0.02Sr0.04(Zr0.45Sn0.47Ti0.08)0.995O3(PLSZST) antiferroelectric ceramics are doped with ZnO, which effectively reduce the sintering temperature. Among them, PLSZST‐1 wt% ZnO is sintered at an ultra‐low sintering temperature (TSintering = 940 °C), which is 330 °C lower than that of PLSZST(TSintering = 1270 °C) without doping ZnO. At the same time, PLSZST‐1 wt%ZnO obtain a recoverable energy density of 4.26J cm−3 and an energy efficiency of 95.5% at 230 kV cm−1. The pulse discharge energy density (Wdis = 3.92 J cm−3) and discharge time (t0.9 = 351 ns) are obtained at 220 kV cm−1, and the current density (CD = 1338A cm−2) and power density (PD = 134MW cm−3) are obtained at 200 kV cm−1. The results provide a possible material basis for Cu internal electrode ceramic capacitors. [ABSTRACT FROM AUTHOR]

Arsenic is a major pollutant in aquatic environments. Due to its high toxicity and poor biodegradability, arsenic has emerged as a significant challenge in the realm of water pollution management. In this study, bamboo shoot shells activated carbon modified with cerium nitrate hexahydrate (Ce‐BAC) is prepared, and its adsorption properties for As (V) and As (III) are investigated. The results indicate that the adsorption capacity of bamboo shoot shells activated carbon (BAC) for As (V) and As (III) is measured to be 3.718 mg/g and 3.527 mg/g, respectively, under the conditions of an activation temperature of 900 °C, activation time of 75 minutes, and pH=7. After modifying it with cerium nitrate hexahydrate, the greatest adsorption capacity of Ce‐BAC for As (V) increases to 16.5 mg/g, and for As (III) to 21.47 mg/g. Moreover, the adsorption process of As (V) and As (III) by BAC and Ce‐BAC in this study exhibits conformity to pseudo‐second order kinetics. These findings indicate that the adsorption performance of As (V) and As (III) by Ce‐BAC has been greatly improved. Therefore, Ce‐BAC exhibits a vast potential in adsorbing both As (V) and As (III), showcasing promising prospects. [ABSTRACT FROM AUTHOR]

Summary: Purple corn anthocyanins have rich nutritional value, but anthocyanins have low stability. The main objective of this study was to screen compounds from the common co‐pigments (polysaccharides, organic acids and colloids) that could improve the stability of anthocyanins and to investigate the effect of different co‐pigments on the stability of anthocyanins in purple corn during heat treatment. There were significant differences in copigmentation effects among different types of co‐pigments. The total anthocyanin retention rate of purple corn without co‐pigments was 15.02%. After copigmentation treatment with different compounds, among the polysaccharides, the total anthocyanin retention rates of 15% fructose and 15% glucose were 37.29% and 52.18% respectively. The copigmentation effects of monosaccharides were better than those of disaccharides, sugar alcohols and cyclodextrins. Among the organic acids, the six co‐pigments were all organic acids containing phenolic rings. The retention rates of anthocyanins were 71.47% and 68.21% for 0.06% tannic acid and 0.1% tartaric acid, respectively, indicating high copigmentation effects. The a* value of purple corn was significantly increased after these treatments, indicating that organic acids had stronger copigmentation effects than polysaccharides. In the colloids, the total anthocyanin retention rate of 2.0% pectin was 43.72%, while 0.5% guar gum had a retention rate of 9.82%. However, low concentrations of guar gum promoted the degradation of anthocyanins, indicating weak copigmentation effects for colloids. [ABSTRACT FROM AUTHOR]

Alternative polyadenylation (APA) generates different 3′‐untranslated regions (3′UTRs) to regulate gene expression and localization, and affects a variety of biological processes. Here, we characterized the 3′UTR dynamics during the oocyte‐to‐zygote transition by analysing our previously reported porcine single‐cell RNA‐seq (scRNA‐seq) datasets (in vitro matured metaphase II (MII) oocytes, in vitro fertilized zygotes (IVF1) and parthenogenetically activated 1‐cell embryos (PA1)). After IVF1 versus MII comparison, dynamic analyses of APA from RNA‐seq (DaPars) method identified 139 mRNAs with significantly different 3′UTRs (padj. ≤.05), mainly enriched in cell cycle, regulation of cyclin‐dependent protein kinase activity, histone modification, mRNA surveillance, and regulation of actin cytoskeleton. For PA1 versus MII comparison, 105 mRNAs with significantly different 3′UTRs (padj. ≤.05) were identified to be mainly enriched in intracellular transport, mitotic spindle organization, cell cycle, pyruvate metabolism and glycolysis/gluconeogenesis. Furthermore, there were 7 mRNAs with more significant 3′UTR differences (|△PDUI| ≥ 0.45 and |log2[PDUI ratio]| ≥ 0.59) respectively in IVF1 versus MII (Lrp2bp, Mtfr2, Nhlrc2, Psip1, Smu1, Ssr1 and Wtap) and PA1 versus MII (Asf1b, Dimt1, Nap1l1, Ncoa4, Nudt21, Pnn and Rpl15) comparisons. Integrative genomics viewer analysis further identified that 3′UTRs of Psip1, Smu1, Ssr1 and Wtap had more than 140 nt average length changes, whereas those of Dimt1, Nap1l1 and Rpl15 were shortened with more than 460 nt. Regulatory elements (PAS, CPE, microRNA binding sites and m6A sites) in 3′UTRs of different lengths were predicted. Our findings provide useful information to further investigate the molecular mechanism of 3′UTR in regulating the oocyte‐to‐zygote transition of pig embryos. [ABSTRACT FROM AUTHOR]

In this paper, two novel algorithms to find the Nash equilibrium solution of the non‐zero‐sum games for continuous‐time input‐affine nonlinear systems are presented. Based on integral reinforcement learning method, the integral‐exploration‐coupled Hamilton‐Jacobi (HJ) equations are derived, which does not contain any information of the system dynamics. Then, based on neural networks approximation, two different adaptive tuning law of weights are given to estimate the approximate solution of the coupled HJ equations. Both two algorithms can estimate the value function and the policy without knowing or identifying the system dynamics. The closed‐loop system stability and the convergence of weights are guaranteed based on Lyapunov analysis. Finally, the simulation results of a two‐player non‐zero‐sum game demonstrate the effectiveness of our algorithms. [ABSTRACT FROM AUTHOR]

Bromoacetophenones are important pharmaceutical intermediates in drug synthesis. In this work, through conditional screening, α‐bromoacetophenone and α,α‐dibromoacetophenone were selectively synthesized using sodium bromide as a bromine source and potassium persulfate as an oxidant. Herein, a novel, green, and selective bromide synthesis reaction was developed. [ABSTRACT FROM AUTHOR]

Background: Platelets are a key component of massive transfusion in treating actively bleeding patients. While optimized for prophylactic transfusions, the effectiveness of the current standard room temperature stored platelets (RPs) in treating actively bleeding patients is not clear. Cold‐stored platelets (CPs) have been shown to have superior hemostatic functions and the potential to extend shelf life. In this study, we explored the effect of using CPs versus RPs in an in vitro transfusion model based on the massive transfusion protocol. Study Design and Methods: RPs or CPs were combined with RBCs and plasma in a 1:1:1 volume ratio to make transfusion packages. Whole blood was collected and then either diluted to 20% hematocrit or mixed with tPA (8.8 μg/ml). By volume, 70% of transfusion package was mixed with 30% whole blood to simulate massive transfusions and analyzed by rotational thromboelastometry. Transfusion package supernatant was analyzed for PAI‐1 activity as well. Results: Both transfusion packages restored the clot characteristics of hemodiluted or hyperfibrinolytic whole blood. Specifically, only transfusion packages made with CPs significantly reduced the maximum clot lysis of hyperfibrinolytic whole blood. PAI‐1 activity in CPs transfusion packages were also significantly higher. Discussion: Transfusion packages containing cold‐stored platelets may be able to restore the blood hemostatic profile of bleeding patients. In addition, transfusion packages made from CPs may provide additional benefit of resisting hyperfibrinolysis in bleeding patients. In trauma where post‐transfusion platelet recovery is less of a concern, CPs are a viable option to restore hemostasis. [ABSTRACT FROM AUTHOR]

Objective: Mononuclear cell infiltration and type I interferon (IFN) system activation play an important role in primary Sjögren's syndrome (SS). We undertook this study to investigate the mechanism of poly(ADP‐ribose) polymerase family member 9 (PARP‐9) on mononuclear cell infiltration triggered by type I IFN. Methods: A proteomic study was conducted in peripheral blood mononuclear cells from patients with primary SS (n = 30) and healthy controls (n = 30) to determine differentially expressed proteins (DEPs) (P < 0.05; fold change >1.20). Labial salivary glands (LSGs) were isolated for hematoxylin and eosin staining and immunohistochemical analysis. CD19+ B cells were purified by magnetic cell sorting for immunofluorescence staining, lentivirus–PARP‐9 transfection, and IFNα treatment experiments. PARP‐9 small interfering RNA (siRNA) and DTX3L siRNA were delivered into female NOD/LtJ female mice to determine their effect. Results: The overexpression of PARP‐9 and CXCL10 as well as their colocalization was confirmed in primary SS. PARP‐9 levels in LSGs rose with increased Chisholm scores in patients with primary SS. PARP‐9 and DTX3L were present in the infiltrating mononuclear cells from salivary glands in female NOD/LtJ mouse models. Additionally, Ingenuity Pathway Analysis networks of DEPs demonstrated that PARP‐9, STAT1, and IFN‐induced protein with tetratricopeptide repeats 1 (IFIT‐1) participated in the IFN‐related pathway. Furthermore, PARP‐9 could up‐regulate the expression of IFIT1 and CXCL10 in B cells. Moreover, PARP‐9 and CXCL10 could be induced by IFNα in B cells. Conclusion: This study is the first to implicate PARP‐9 as a regulator of infiltration of mononuclear cells in primary SS progression and to reveal that PARP‐9 increases CXCL10 expression through up‐regulating IFIT‐1, which is mediated by the phosphorylation of STAT1. PARP‐9 might therefore be a novel therapeutic target for primary SS. [ABSTRACT FROM AUTHOR]

Relationships between xylem anatomical traits and cavitation resistance have always been a major content of plant hydraulics. To know how plants cope with drought, it is extremely important to acquire detailed knowledge about xylem anatomical traits and assess the cavitation resistance accurately. This study aims to increase our knowledge in the methods determining cavitation resistance and xylem anatomical traits. We selected a semi‐ring‐porous species, Hippophae rhamnoides L., and a diffuse‐porous species, Corylus heterophylla F., to clarify the reasons for the difference in cavitation resistance based on detailed xylem anatomical traits and reliable vulnerability curves (VCs). Both Cavitron and bench dehydration (BD) were used to construct VCs. Xylem anatomical traits, including pit membrane ultrastructure of these two species, were determined. The VCs obtained by the two different techniques were of different types for H. rhamnoides, its Cavitron VCs might be unreliable because of open‐vessel artifacts. On the basis of BD VCs, H. rhamnoides showed higher cavitation resistance than C. heterophylla, and this is attributed to its low vessel connectivity as well as non‐porous and thicker pit membranes. [ABSTRACT FROM AUTHOR]

Disk transparent ceramics with multilayer composite structure serves well as laser gain medium because of its excellent thermal and optical properties. For such a type of material, the preparation of corresponding outstanding slurry is the first yet most essential step, and it may determine the quality of both subsequent green tape and the sintered ceramics. In this work, the tape‐casting slurry with typically pseudoplastic behavior was carefully modulated in the mixture solvent of anhydrous ethanol and ethyl acetate, and its rheological property was systematically investigated using fine‐controlled rotary rheometer. The obtained result reveals 4wt.% fish oil to be the best dispersed agent. With the obtained slurry for tape‐casting followed by lamination and warm isostatic‐pressing, the multilayer ultrathin TCs was successfully fabricated via high‐temperature vacuum sintering technology. The obtained full‐dense microstructure with high optical quality may endow the studied ceramic with great potential for highly efficient solid‐state laser gain medium. [ABSTRACT FROM AUTHOR]

Human tissues are sophisticated ensembles of various distinct cell types encapsulated in the biomechanical cues of the extracellular matrix. It has been known matrix stiffness plays a pivot role in cellular events and tissue‐scale biological processes. Thus, materials that can mimic mechanical environments of tissues in vitro and possess wide, physiologically relevant elasticity are highly desirable. Hydrogels provide a good cell platform to mimic native cellular environment. However, the limited stiffness tunability, and hinders the efforts to reproduce the biomechanical microenvironment of many in vivo progresses. These problems have been addressed by the recently emerged great quantity of exquisitely designed smart hydrogels. Smart hydrogels that respond sensitively to external stimuli are good choices due to the convenience in regulating their mechanical properties. In this review, we summarize the latest progress in the development of stimuli‐responsive hydrogels as a cell carrier (platform for cell culture) which spans a wide range of stiffness. Different kinds of smart hydrogels corresponding to various stimuli, including pH, temperature, light, metal ions, and forces, are introduced and their stiffness modulation through physicochemical procedures are reported. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: It is known that an interruption of acoustic input in early life will result in abnormal development of the auditory system. Here, we further show that this negative impact actually spans beyond the auditory system to the hippocampus, a system critical for spatial memory. Methods: We induced a temporary conductive hearing loss (TCHL) in P14 rats by perforating the eardrum and allowing it to heal. The Morris water maze and Y‐maze tests were deployed to evaluate spatial memory of the rats. Electrophysiological recordings and anatomical analysis were made to evaluate functional and structural changes in the hippocampus following TCHL. Results: The rats with the TCHL had nearly normal hearing at P42, but had a decreased performance with the Morris water maze and Y‐maze tests compared with the control group. A functional deficit in the hippocampus of the rats with the TCHL was found as revealed by the depressed long‐term potentiation and the reduced NMDA receptor‐mediated postsynaptic current. A structural deficit in the hippocampus of those animals was also found as revealed the abnormal expression of the NMDA receptors, the decreased number of dendritic spines, the reduced postsynaptic density and the reduced level of neurogenesis. Conclusions: Our study demonstrates that even temporary auditory sensory deprivation in early life of rats results in abnormal development of the hippocampus and consequently impairs spatial memory in adulthood. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes, a common food borne bacterial pathogen, could survive in stress conditions applied in food production such as cold environments. Twenty-eight strains of L. monocytogenes under cold stress were subjected to MALDI-TOF MS analysis and compared with control strains under normal growth conditions. The resulting protein mass finger printings were visualized by phyloproteomic cluster and self-organized map (SOM). It was observed that after cold-stressed treatment, all strains exhibited change of mass finger printings. In most strains, the variations of the fingerprinting profiles were significant. The diversity in protein fingerprinting of L. monocytogenes after cold stress was also improved. The strain-level differentiation of the stressed L. monocytogenes would not only improve the understanding of bacterial responses to cold stress but also facilitate classification and detection of stressed bacteria in food industry. Practical applications Listeria monocytogenes that causes lethal listeriosis could survive in cold-stressed treatment and pose high risk to food safety. However, the entire picture of the physiology of stress response adaptation of this strain is still unknown. The protein fingerprinting analysis of the cold-stressed L. monocytogenes provided an entire picture of phenotypic stress response adaptation at strain level and helped to understand bacterial resistance to cold stress. Additionally, the study on the peptide fingerprints changes, covering 28 strains of L. monocytogenes from different sources would be particularly valuable for the strain-level differentiation and detection of stressed bacteria in food industry. [ABSTRACT FROM AUTHOR]

Objective: Soft tissue (ST) dehiscence with graft exposure is a frequent complication of vertical augmentation. Flap dehiscence is caused by failure to achieve tension-free primary wound closure and by the impairment of flap microcirculation due to surgical trauma. Soft tissue expansion (STE) increases ST quality and quantity prior to reconstructive surgery. We hypothesized that flap preconditioning using STE would reduce the incidence of ST complications after bone augmentation and that optimized ST healing would improve the outcome of bone regeneration. Materials and methods: Self-filling tissue expanders were implanted in mandibular bone defects in ten beagle dogs. After expansion, alloplastic scaffolds were placed for vertical bone augmentation in STE sites and in control sites without STE pre-treatment. ST flap microcirculation was analysed using laser Doppler flowmetry. The incidence of graft exposures was evaluated after 2 weeks. Bone formation was assessed after 2 months, using histomorphometry and immunohistochemistry. Results: Test sites showed significantly less impairment of perfusion and faster recovery of microcirculation after bone augmentation. Furthermore, no flap dehiscences occurred in STE sites. Bone regeneration was found in both groups; however, significantly greater formation of new bone was detected in test sites with preceding STE. Conclusions: Preconditioning using STE improved ST healing and bone formation after vertical augmentation. The combination of STE and the subsequent placement of alloplastic scaffolds may facilitate the reconstruction of severe bone defects. [ABSTRACT FROM AUTHOR]

Objectives We investigated the effect of soft tissue expansion ( STE) on vertical ridge augmentation with regard to the incidence of wound dehiscences and the impairment of microcirculation in dogs, and the applicability of laser Doppler flowmetry ( LDF) to explore the relation between microcirculation and wound healing. Material and methods Bone defects were created on both mandibular sides in ten beagle dogs by extraction of premolars and removal of bone. Six weeks later, self-filling tissue expanders were implanted in randomly assigned test sites. After 5 weeks of expansion, vertical augmentation was carried out in test and control sites using calvarial onlay grafts side by side with granular biphasic calcium phosphate covered with a resorbable polyethylene glycol membrane. Microcirculation was evaluated with laser Doppler flowmetry ( LDF). The incidence of wound dehiscences was evaluated after 2 weeks. The validity of LDF to predict dehiscences was evaluated by construction of receiver operating characteristic ( ROC) curves. Results After augmentation, test sites showed significantly better perfusion than control sites without preceding STE ( P = 0.012). Three days after surgery, perfusion was still significantly decreased in control sites ( P = 0.005), while microcirculation in test sites had returned to pre-surgical levels. After 2 weeks, healing in test sites was good, whereas eight dehiscences were found in control sites ( P = 0.002). ROC curves showed that microcirculation levels immediately after augmentation surgery significantly predicted subsequent wound dehiscences ( AUC = 0.799, CI 0.642-0.955, P = 0.006). Conclusions Laser Doppler flowmetry is suitable for evaluation of soft tissue microcirculation after ridge augmentation. STE reduced the impairment of microcirculation caused by vertical ridge augmentation and decreased the incidence of wound dehiscences in the investigated animal model. [ABSTRACT FROM AUTHOR]

The increasing frequency and intensity of heat waves caused significant damages to urban woody species, and the different leaf structures between evergreen and deciduous species may be closely related to leaf heat tolerance. However, whether the different leaf structural traits of evergreen and deciduous plants contribute to their different responses under heat waves is still unclear.During the record‐breaking and long‐lasting 2022 summer heat waves in China, we investigated the relationships between leaf thermal indices and leaf structural traits of 36 urban woody species in four cities along the Yangtze River.We found that all the four thermal indices were significantly but weakly related with leaf damage status. The critical temperature that causes the initial 15% damage to photosystem II (Tcrit) may serve as a sensitive measure of heat tolerance. Evergreen species suffered less leaf damage during the heat waves and exhibited higher leaf heat tolerance, thicker leaves than deciduous species. Tcrit was significantly correlated with leaf mass per area, leaf thickness and thickness of spongy tissue.Synthesis. Urban woody species with higher Tcrit, leaf mass per area and leaf thickness tend to be more tolerant to heat stress. This study provides insights for predicting leaf heat tolerance of urban woody plants in subtropical China and their physiological and ecological responses to severe heat waves. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of submucosal implantation of self-filling osmotic tissue expanders on mucosal microcirculation. Material and methods In ten beagle dogs, all premolars were extracted on both sides of the mandible. Tooth-supporting bone and excess soft tissue were removed to mimic a severely resorbed edentulous ridge. Six weeks later, tissue expanders with 0.7 ml final volume were implanted into a submucosal pouch at randomly selected test sites, while contralateral sites served as untreated controls. Microcirculation was assessed in perfusion units ( PU) before surgery, after local anaesthesia, directly after surgery, and after 1 and 3 days, using Laser Doppler flowmetry. Results Local anaesthesia caused a significant decrease of blood flow from baseline (zero) to −6.4 PU (median; Q1 −10.5; Q3 −0.9; P = 0.006); however, no additional significant decrease was recorded after completion of surgery. Blood flow showed significant increases to −3.6 PU (median; Q1 −11.3, Q3 2.1; P = 0.02) and −4.0 PU (median; Q1 −9.2, Q3 1.1; P = 0.013) after 1 and 3 days, respectively, when compared to the measurements obtained after application of local anaesthesia and completion of surgery. Blood flow had returned to unimpaired baseline levels 1 day after surgery ( P > 0.05). Conclusions Submucosal implantation of self-filling osmotic tissue expanders results in only momentary disturbance of microcirculation. The minor impairment of perfusion may explain the consistently good outcomes of submucosal implantation of these tissue expanders. [ABSTRACT FROM AUTHOR]

We propose a novel single-cell chemical proteomics (SCCP) strategy to profile low-abundance membrane proteins in single cells. In this approach, the membrane protein GB1 and its splicing variants were targeted on cultured cell lines and primary neurons using a specifically designed activity-based probe. The functionally labeled single cells were encapsulated in individual buffer droplets on a PDMS microwell array, and were further picked up one at a time and loaded into a capillary electrophoresis system for cell lysis, separation, and laser-induced fluorescence detection of the targeted proteins. The results revealed the expression of GB1 splicing variants in HEK and MEF cells, which was previously only suggested at the transcriptional level. We further applied this method to investigate single primary cells and observed significant heterogeneity among individual mouse cerebellar granule neurons. Interference experiments with GB1 antagonist and agonist validated this observation. [ABSTRACT FROM AUTHOR]

We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11‐q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure‐free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti‐seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly. [ABSTRACT FROM AUTHOR]

New Zircon U-Pb Dating of the Tuanliangzi Formation in South Lancangjiang Zone, Western Yunnan: Implications for the Tethyan Evolution of the Simao Block. [Extracted from the article]

Through evolutionary processes, helicoidal structures have been proven to exhibit exceptional load‐carrying capacity and impact resistance performance. To date, extensive experimental and numerical studies have been carried out on their impact behaviors, while few relevant analytical studies have been reported even though it is urgently needed for the preliminary assessment of structure design and optimization. In this work, based on the first shear deformation theory (FSDT) and the improved linearized Hertzian contact method, an analytical model for low velocity impact (LVI) performances of helicoidal laminates with arbitrary layups is developed. Therein, the post‐impact damage is taken into account according to continuum damage mechanics (CDM). Comparisons of load‐carrying capacity and energy‐absorbed performance between the proposed model prediction and the existing experimental data\numerical results have been made for verification. Besides, LVI behaviors of conventional laminates with unidirectional distribution andcross‐ply arrangement are discussed. Moreover, the role of rotation angle, impact velocity and the plate dimension on helicoidal laminates' LVI performances are analyzed quantitatively. There is evidence that helical layouts are better able to absorb energy and delay the in‐plane damage. Highlights: The LVI responses of bio‐inspired single‐helicoidal (SH) and double‐helicoidal (DH) composite laminate are studied.An effective model to predict the LVI responses considered the post‐impact damage is developed.A comparison of the LVI performance of single‐helicoidal structures with various lay‐up schemes is carried out.DH structure has better low velocity impact resistance than SH structure when the rotation angle shares the same. [ABSTRACT FROM AUTHOR]

ChinaMu is the largest sequence‐indexed Mutator (Mu) transposon insertional library in maize (Zea mays). In this study, we made significant improvements to the size and quality of the ChinaMu library. We developed a new Mu‐tag isolation method Mu‐Tn5‐seq (MuT‐seq). Compared to the previous method used by ChinaMu, MuT‐seq recovered 1/3 more germinal insertions, while requiring only about 1/14 of the sequencing volume and 1/5 of the experimental time. Using MuT‐seq, we identified 113,879 germinal insertions from 3,168 Mu‐active F1 families. We also assembled a high‐quality genome for the Mu‐active line Mu‐starter, which harbors the initial active MuDR element and was used as the pollen donor for the mutation population. Using the Mu‐starter genome, we recovered 33,662 (15.6%) additional germinal insertions in 3,244 (7.4%) genes in the Mu‐starter line. The Mu‐starter genome also improved the assignment of 117,689 (54.5%) germinal insertions. The newly upgraded ChinaMu dataset currently contains 215,889 high‐quality germinal insertions. These insertions cover 32,224 pan‐genes in the Mu‐starter and B73Ref5 genomes, including 23,006 (80.4%) core genes shared by the two genomes. As a test model, we investigated Mu insertions in the pentatricopeptide repeat (PPR) superfamily, discovering insertions for 92% (449/487) of PPR genes in ChinaMu, demonstrating the usefulness of ChinaMu as a functional genomics resource for maize. [ABSTRACT FROM AUTHOR]

The decline in female fertility as age advances is intricately linked to the diminished developmental potential of oocytes. Despite this challenge, the strategies available to enhance the quality of aged oocytes remain limited. Epigallocatechin‐3‐gallate (EGCG), characterised by its anti‐inflammatory, antioxidant and tissue protective properties, holds promise as a candidate for improving the quality of maternally aged oocytes. In this study, we explored the precise impact and underlying mechanisms of EGCG on aged oocytes. EGCG exhibited the capacity to enhance the quality of aged oocytes both in vitro and in vivo. Specifically, the application of EGCG in vitro resulted in noteworthy improvements, including an increased rate of first polar body extrusion, enhanced mitochondrial function, refined spindle morphology and a reduction in oxidative stress. These beneficial effects were further validated by the improved fertility observed among aged mice. In addition, our findings propose that EGCG might augment the expression of Arf6. This augmentation, in turn, contributes to the assembly of spindle‐associated F‐actin, which can contribute to mitigate the aneuploidy induced by the disruption of spindle F‐actin within aged oocytes. This work thus contributes not only to understanding the role of EGCG in bolstering oocyte health, but also underscores its potential as a therapeutic intervention to address fertility challenges associated with advanced age. [ABSTRACT FROM AUTHOR]

The repair of bone defects in diabetes remains a major challenge in the field of biomedicine because of the disturbance of bone immune homeostasis and the susceptibility of exposed wounds to bacterial infection. Clinically, immunoregulation by removing excessive reactive oxygen species (ROS) effectively promotes diabetic bone defect repair. However, aggressive ROS clearance can disrupt ROS homeostasis, making ROS‐mediated polarization of M2 macrophages in the process of tissue healing of diabetes be difficult. Herein, an ultrathin defective tungsten oxide (WOx) nanoribbon with high oxygen vacancies to simultaneously achieve moderate scavenging of ROS and high broad‐spectrum photothermal antibacterial activity to promote diabetic bone defect repair is reported. It is demonstrated that the moderate ROS clearance ability of WOx nanoribbons can remodel metabolic patterns for achieving 86.3% M2 macrophage induction in a high glucose microenvironment. This high induction efficiency combined with excellent photothermal antibacterial ability of WOx nanoribbons markedly alleviated the inflammatory reaction and efficiently facilitated the repair of bone defects infected with methicillin‐resistant Staphylococcus aureus (S. aureus) in C57BLKS/J (BKS)‐diabetic (BKS‐db) mice. [ABSTRACT FROM AUTHOR]

Near‐infrared (NIR) responsive smart drug delivery systems could provide efficient osteogenesis through the synergy of heat and drugs. However, such systems are hampered by an inability to allow supersensitive drug release through mild heat. Here superior osteogenesis is demonstrated using a biocompatible dexamethasone (Dex)‐loaded MXene‐poly(N‐isopropylacrylamide)‐co‐N‐(Hydroxymethyl) acrylamide hydrogel capable of the supersensitive release of Dex at ≈42 °C upon NIR irradiation. Furthermore, the hydrogel can significantly promote bone regeneration under NIR irradiation due to the synergistic anti‐apoptosis and osteogenic differentiation of bone‐derived mesenchymal stem cells induced by the mild heat and supersensitive release of Dex. The resulting osteogenesis efficiency of hydrogels surpass efficiencies previously reported for heat and drug stimulation and their combination. The synergistic osteogenesis strategy is characterized by near‐instantaneous, noninvasive, and precise treatment through temporal NIR irradiation. [ABSTRACT FROM AUTHOR]

Metal halide perovskites have witnessed great success in green, red, and near‐infrared light‐emitting diodes (LEDs), yet blue LEDs still lag behind. Reducing undesired energetic disorders – broad n‐phases and halide segregation – is considered as the most critical strategy to further improve the performances. Here, the study reports a newly designed and synthesized di‐ammonium ligand with rigid π‐conjugated rings and additional methyl groups to construct Dion–Jacobson (DJ) structure. Augmented coordination from the extra ammonium site and increased effective bulkiness from methyl groups lead to better distribution control over conventional mono‐ammonium ligands. This enhances the radiative recombination of blue emissions in the film with homogeneous energy landscape and improved surface morphology, as evidenced by a series of imaging and mapping techniques. As a result, it demonstrates DJ perovskite LEDs (PeLEDs) with peak external quantum efficiencies of ≈4% at 484 nm and ≈11% at 494 nm, which are among the top reported for pure DJ phase‐based PeLEDs in the corresponding wavelength regions. The results deepen the understanding of regulating energetic disorders in perovskite materials via molecular engineering. [ABSTRACT FROM AUTHOR]

The article reports on the research study on the first Discovery and Zircon U‐Pb Dating of the Early Ordovician Granitoids in the area of Lincang Batholith, Western Yunnan. Implications of Proto‐Tethyan Orogeny in Sanjiang Region, South West China are mentioned. From Petrological and geochronological data it could be concluded that Ordovician magmatism had occured in Lincang batholith.

The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age‐associated down‐regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF‐16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF‐16 translocates into the nucleus in aged wild‐type worms and activates the expression of hundreds of genes in response to age‐associated cellular stress. Most of the age‐dependent DAF‐16 targets are different from the canonical DAF‐16 targets downstream of insulin signaling. This and other evidence suggest that activation of DAF‐16 during aging is distinct from activation of DAF‐16 due to reduced signaling from DAF‐2. Further analysis showed that it is due in part to a loss of proteostasis during aging. We also found that without daf‐16, dramatic gene expression changes occur as early as on adult day 2, indicating that DAF‐16 acts to stabilize the transcriptome during normal aging. Our results thus reveal that normal aging is not simply a process in which the gene expression program descends into chaos due to loss of regulatory activities; rather, there is active transcriptional regulation during aging. [ABSTRACT FROM AUTHOR]

Herein, dual‐tunable structural colors generated from liquid‐infused, robust silsesquioxane aerogels due to the specific light scattering by the aerogel skeleton in liquids with matching refractive indices, are reported. The colors are tunable by changing the temperature and the composition of the liquid that roots from the coherence between the colors and the refractive index of the infused liquid. The finding provides new insights and tools for constructing structural colors and light management. It also opens applications of stimuli‐responsive smart windows, displays, and sensors. Taking advantage of the penetrable light of selected wavelength, the 3D structures of aerogel skeletons are reconstructed by an optical method, which provides a facile alternative approach to characterizing aerogel structure and will be instrumental to the understanding of the relationship between skeleton structure and mechanical property of porous 3D structures. [ABSTRACT FROM AUTHOR]

The ability to tune the resonant frequency of a self‐assembled ultrasonic metamaterial with mesoscale spatial resolution, after fabrication, by up to 250% is demonstrated. This tunability is achieved by the microlensing‐enabled modification of nanocontact features, wherein the metamaterial resonant elements "dig in" to the substrate. In addition to tunability exceeding prior MHz–GHz frequency ultrasonic metamaterial examples, the system presented herein can be tuned after assembly at a spatial resolution commensurate with the laser spot's diameter. It is posited that these aforementioned advantages will enable a new class of ultrasonic gradient index devices, such as ultrasonic elastic wave cloaks, that can be manufactured in a scalable manner and then rapidly tuned. Finally, it is expected that this large tunability at ultrasonic frequencies will have broader application to areas including optomechanics, acoustoplasmonics, quantum‐mechanical oscillators, and adhesion control. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P <.01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes. [ABSTRACT FROM AUTHOR]

Background: Optimization of risk stratification is important for facilitating prognoses and therapeutic decisions regarding diffuse large B‐cell lymphoma (DLBCL). However, a simple and applicable prognostic tool is lacking for individuals with human immunodeficiency virus (HIV)‐related DLBCL in the era of combined antiretroviral therapy (cART). Methods: This retrospective multicenter observational study included 147 HIV‐related DLBCL patients with histologically confirmed DLBCL from 2013 to 2020. The total group was divided into training (n = 78) and validation (n = 69) cohorts to derive the best prognostic score. Clinicopathological and characteristic biomarkers correlated with clinical outcomes were analyzed. Results: Age, Ann Arbor stage, lactate dehydrogenase (LDH) ratio, bulky disease, and red blood cell distribution width (RDW) ratio retained robust independent correlations with overall survival (OS) in multivariate analysis. A new and practical prognostic model was generated and externally validated, classifying patients into three categories with significantly different survival rates. Moreover, the new index outperformed the International Prognostic Index (IPI) score (area under the curve values of 0.94 vs. 0.81 in the training cohort and 0.85 vs. 0.74 in the validation cohort, C‐indices of 0.80 vs. 0.70 in the training cohort and 0.74 vs. 0.70 in the validation cohort, and integrated discrimination improvement values of 0.203 in the training cohort and 0.175 in the validation cohort) and was better at defining intermediate‐ and high‐risk groups. The calibration curves performed satisfactorily for predicting 3‐year OS in the training and validation cohorts. Conclusions: We developed and validated a simple and feasible prognostic model for patients with HIV‐related DLBCL that had more discriminative and predictive accuracy than the IPI score for risk stratification and individualized treatment in the cART era. [ABSTRACT FROM AUTHOR]

Total fertilization failure (TFF), which refers to fertilization failure in all mature oocytes, accounting for 5%–10% of in vitro fertilization (IVF) cycles and 1%–3% of intracytoplasmic sperm injection (ICSI) cycles in human. In this study, we recruited three unrelated primary infertile men with repeated cycles of TFF and performed whole‐exome sequencing to identify the potential pathogenic variants. We identified homozygous or compound‐heterozygous variants of paternal‐effect genes ACTL7A and PLCZ1 that followed a Mendelian recessive inheritance pattern. Novel homozygous nonsense variant in ACTL7A [c.C146G: p.S49*] was identified in case 1, who came from a consanguineous family. Ultrastructural observation of ACTL7A‐mutated spermatozoa by transmission electron microscopy (TEM) indicated that apparent increased thickness of perinuclear matrix and the acrosome was detached from the nuclear envelop. Besides, two novel compound‐heterozygous variants in PLCZ1 were identified in case 2 [c.1174+3A>C:p.?; c.A1274G:p.N425S] and case 3 [c.136‐1G>C:p.?; c.G1358A:p.G453D]. Mutated spermatozoa from case 2 with reduced expression of PLCZ1 showed apparent acrosome detachment by TEM analysis. And ICSI with assisted oocyte activation (ICSI‐AOA) treatment can partly rescue the TFF. Taken together, our findings revealed that novel biallelic variants in the paternal‐effect genes ACTL7A and PLCZ1 were associated with human TFF, which expanding the spectrum of genetic causes and facilitating the genetic diagnosis of male infertility with TFF. [ABSTRACT FROM AUTHOR]

In the coldest part of winter, water uptake is blocked by the frozen soil and frozen stems known as 'frost drought' causing severe embolisms in woody plants. Frost drought in stems was simulated in a centrifuge by a synergy between freeze–thaw cycles and the different tensions induced by changing the rotation speed. Frost fatigue was defined as a reduction of embolism resistance after a freeze–thaw cycle and determined from 'vulnerability curves', which showed percent losses of conductivity vs tension (positive value) or xylem pressure (negative value). Different tensions combined with a controlled freeze–thaw cycle were induced to investigate the effects on frost resistance over the course of year. During the growing season, Acer mono Maxim. developed significant frost fatigue, and a significant positive correlation was found between frost fatigue response and exogenous tension. During the dormant season, A. mono showed very high embolism resistance to frost drought, even under a tension of 2 MPa. When the exogenous tension was increased to 3 MPa while the stem was frozen, significant frost fatigue occurred. Longer freezing times had more serious effects on frost fatigue in A. mono. A hypothesis was raised that at the same low temperature, the severer the drought (higher tension) when stems were frozen, the higher frost fatigue response would be induced. [ABSTRACT FROM AUTHOR]

Objective To evaluate the influence of Scoliosis Research Society (SRS)- Schwab sagittal modifiers of pelvic incidence minus lumbar lordosis mismatch ( PI-LL) on clinical outcomes for adult degenerative scoliosis ( ADS) after long posterior instrumentation and fusion. Methods This was a single-institute, retrospective study. From 2012 to 2014, 44 patients with ADS who underwent posterior instrumentation and fusion treatment were reviewed. Radiological evaluations were investigated by standing whole spine (posteroanterior and lateral views) X-ray and all radiological measurements, including Cobb's angle, LL, PI, and the grading of vertebral rotation, were performed by two experienced surgeons who were blind to the operations. The patients were divided into three groups based on postoperative PI-LL and the classification of the SRS- Schwab: 0 grade PI-LL (<10°, n = 13); + grade PI-LL (10°-20°, n = 19); and ++ grade PI-LL (>20°, n = 12). The clinical outcomes were assessed according to Japanese Orthopaedic Association ( JOA) score, Oswestry Disability Index ( ODI), Visual Analog Scale ( VAS), Lumbar Stiffness Disability Index ( LSDI), and complications. Other characteristic data of patients were also collected, including intraoperative blood loss, operative time, length of hospital stay, complications, number of fusion levels, and number of decompressions. Results The mean operative time, blood loss, and hospital stay were 284.5 ± 30.2 min, 1040.5 ± 1207.6 mL, and 14.5 ± 1.9 day. At the last follow-up (2.6 ± 0.6 years), the radiological and functional parameters, except the grading of vertebral rotation, were all significantly improved in comparison with preoperative results ( P < 0.05), but it was obvious that an ideal PI-LL (≤10°) was not achieved in some patients. Significant differences were only observed among the three groups in the ODI and LSDI. Patients with + grade PI-LL seemed to have the best surgical outcome compared to those with 0 and ++ grade PI-LL, with the lowest ODI score (+ grade vs 0 grade, 17.3 ± 4.9 vs 26.0 ± 5.4; + grade vs ++ grade, 17.3 ± 4.9 vs 32.4 ± 7.3; P < 0.05) and lower LSDI (+ grade vs 0 grade, 1.6 ± 1.0 vs 3.5 ± 0.5, P < 0.05; + grade vs ++ grade, 1.6 ± 1.0 vs 0.6 ± 0.5, P > 0.05). A Pearson correlation analysis further demonstrated that LSDI was negatively associated with PI-LL. Furthermore, the incidence rate of postoperative complications was lower in patients with + grade PI-LL (1/19, 5.26%) than that in patients with 0 (2/13, 15.4%) and ++ grade PI-LL (3/12, 25%). Conclusion Our present study suggest that the ideal PI-LL may be between 10° and 20° in ADS patients after long posterior instrumentation and fusion. [ABSTRACT FROM AUTHOR]

Objectives: A classification system for endocervical adenocarcinoma (ECA) based on high‐risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV‐independent and HPV‐associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features. Methods: We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV‐independent ECAs and 50 HPV‐associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed. Results: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV‐independent ECAs, including eight gastric‐type ECAs (G‐ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV‐independent ECAs. Among HPV‐associated ECAs, CLDN18 (M) expression levels in intestinal‐type (I‐ECAs) and usual‐type ECAs (U‐ECAs) were significantly different from those in invasive stratified mucin‐producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal‐type and 39.4% (13/33) of usual‐type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001). Conclusion: Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV‐independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV‐associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs. [ABSTRACT FROM AUTHOR]

A photo‐induced three‐component coupling reaction of quinoxalinones with unactivated alkenes and azidobenziodoxolone (ABX, Zhdankin reagent) was developed. The protocol provides an efficient approach for the synthesis of various bioactive organoazides with quinoxalinone scaffold in moderate to good yields under mild conditions. This reaction is environmentally friendly avoiding the use of expensive transition‐metal photocatalysts and stoichiometric oxidants. [ABSTRACT FROM AUTHOR]

Knowledge of the transcription factor binding landscape (TFBL) is necessary to analyze gene regulatory networks for important agronomic traits. However, a low‐cost and high‐throughput in vivo chromatin profiling method is still lacking in plants. Here, we developed a transient and simplified cleavage under targets and tagmentation (tsCUT&Tag) that combines transient expression of transcription factor proteins in protoplasts with a simplified CUT&Tag without nucleus extraction. Our tsCUT&Tag method provided higher data quality and signal resolution with lower sequencing depth compared with traditional ChIP‐seq. Furthermore, we developed a strategy combining tsCUT&Tag with machine learning, which has great potential for profiling the TFBL across plant development. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the association between the IRAK4 polymorphism rs4251545 and the severity of enterovirus 71 (EV71) infection in Chinese children. Methods: We analyzed the IRAK4 polymorphism rs4251545 in 617 EV71‐infected patients and 410 controls using the improved multiplex ligation detection reaction. IRAK4 mRNA expression was tested by qRT‐PCR. Serum concentrations of IL‐6 and NF‐κB were detected using ELISA. Results: The frequencies of the GA + AA genotype and A allele in the mild EV71 infection group and in the severe EV71 infection group were significantly higher than those in the normal control group. The frequency of the GA + AA genotype and A allele in severely infected EV71 patients was markedly higher than that in mildly infected EV71 patients. IRAK4 mRNA expression in mildly infected EV71 patients and severely infected patients was significantly higher than that in the control group. IRAK4 mRNA expression in GA + AA genotypes in both mild and severe EV71 infection groups was significantly higher than that in patients with the GG genotype. IL‐6 concentration and the ratio of IL‐6/NF‐κB in severe EV71 cases were significantly lower in patients with the GA + AA genotype than in those with the GG genotype. The ratio of IL‐6/NF‐κB was distinctly higher in severely infected EV71 patients than in mildly infected and control subjects. Conclusions: The IRAK4 polymorphism rs4251545 was associated with the susceptibility and severity of EV71 infection. The A allele is a susceptible factor in the development of severe EV71 infection in Chinese children. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastrointestinal (GI) dysmotility in acute pancreatitis (AP) aggravates inflammation and results in severe complications. This study aimed to explore effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) on abdominal pain, GI dysmotility, and inflammation in AP patients. Methods: Forty‐two AP patients were blindly randomized to receive TEA (n = 21) at acupoints PC6 and ST36 or Sham‐TEA (n = 21) at sham points for 2 days. Symptom scores, gastric slow waves, autonomic functions (assessed by spectral analysis of heart rate variability), circulatory levels of motilin, ghrelin, and TNF‐α were measured before and after the treatment. Sixteen healthy controls (HCs) were also included without treatment for the assessment of gastric slow waves and biochemistry. Key Results: Compared with Sham‐TEA, TEA decreased abdominal pain score (2.57 ± 1.78 vs. 1.33 ± 1.02, p < 0.05), bloating score (5.19 ± 1.21 vs. 0.76 ± 0.99, p < 0.001), the first defecation time (65.79 ± 19.51 h vs. 51.38 ± 17.19 h, p < 0.05); TEA, but not Sham‐TEA, improved the percentage of normal gastric slow waves by 41.6% (p < 0.05), reduced AP severity score (5.52 ± 2.04 vs. 3.90 ± 1.90, p < 0.05) and serum TNF‐α (7.59 ± 4.80 pg/ml vs. 4.68 ± 1.85 pg/ml, p < 0.05), and upregulated plasma ghrelin (0.85 ± 0.96 ng/ml vs. 2.00 ± 1.71 ng/ml, p = 0.001) but not motilin (33.08 ± 22.65 pg/ml vs. 24.12 ± 13.95 pg/ml, p > 0.05); TEA decreased sympathetic activity by 15.0% and increased vagal activity by 18.3% (both p < 0.05). Conclusions & Inferences: TEA at PC6 and ST36 administrated at early stage of AP reduces abdominal pain, improves GI motility, and inhibits inflammatory cytokine, TNF‐α, probably mediated via the autonomic and ghrelin mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Neuroendocrine cervical cancer (NECC) is a rare cervical cancer with high aggressivity that causes poor prognosis even in the early stage. Given other neuroendocrine carcinomas and other types of cervical cancer have been proved to have expression of programmed cell death protein 1 ligand 1(PD‐L1) and poly ADP‐ribose polymerase‐1(PARP1), we would measure and analyze these proteins in this invasive cancer. The purpose of this study is to investigate the application value of PD‐1/PD‐L1 and PARP1 inhibitors in NECC. Methods: The NECC cases in our center with formalin‐fixed paraffin‐embedded tissue blocks were collected, and immunohistochemical (IHC) staining of PD‐L1, PARP1, Mismatch repair proteins (MMRs), and P53 was performed. Chi‐square test was used to analyze associations between various protein expressions. We analyzed the efficacy of immunotherapy in a recent patient with secondary recurrence after two courses of chemotherapy. Results: After rigorous screening, 20 cases were finally included. Three cases did not undergo surgical treatment because of their advanced stage. Twelve (60%) developed distant metastases or relapsed within five years, and most of them within two years. The positive rate of PD‐L1 and PARP1 were 70% and 75% respectively. Among all the cases, microsatellite instability (MSI) was seen in six cases (30%) and abnormal p53 expression was in 15 patients (75%). PD‐L1 was associated with PARP1 expression in the MSI subgroup. The patient treated with chemotherapy + VEGF inhibitor (VEGFi) + programmed cell death protein 1(PD‐1) inhibitor had an excellent improvement in clinical symptoms, tumor markers, and mass size. Conclusion: The IHC results of PD‐L1, PARP1, and MMRs suggested that NECC was the target of immunotargeted therapy. Our case confirmed that immune checkpoint therapy was effective in patients with PD‐L1 positive and MMRs loss. Considering the clinical practicability, more cases should be collected, and effective biomarkers still need to be further searched. [ABSTRACT FROM AUTHOR]

Introduction: Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. Material and methods: We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze‐all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n = 191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n = 96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n = 1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. Results: For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P =.009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P =.071). Conclusions: The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single‐blastocyst frozen embryo transfer. [ABSTRACT FROM AUTHOR]

Mimicking the endogenous physical microenvironment is a promising strategy for biomaterial‐mediated tissue regeneration. However, precise control of physical cues such as electric/magnetic fields within extracellular environments to facilitate tissue regeneration remains a formidable challenge. Here, remote tuning of the magnetoelectric microenvironment is achieved by a built‐in CoFe2O4/poly(vinylidene fluoridetrifluoroethylene) [P(VDF‐TrFE)] magnetoelectric membrane for effective bone regeneration. The magnetoelectric microenvironment from the nanocomposite membranes promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BM‐MSCs) and enhances bone defect regeneration by increasing cellular exposure and integrin binding to arginylglycylaspartic acid peptide, as predicted by molecular dynamics simulations. Moreover, BM‐MSCs are directed to the osteogenic lineage by osteoimmuomodulation which involves accelerating transition from an initial inflammatory immune response to a pro‐healing regenerative immune response. This work offers a strategy to mimic the magnetoelectric microenvironment for achieving precise and effective tissue regenerative therapies, as well as provides fundamental insights into the biological effects driven by the built‐in magnetoelectric membrane, which can be remotely tuned to precisely modulate osteogenesis in situ. [ABSTRACT FROM AUTHOR]

Variants of tubulin beta 8 class VIII (TUBB8) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi‐pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development. [ABSTRACT FROM AUTHOR]

Potassium ion capacitors (PIC) have been extensively explored as an economically favorable substitute for their well‐developed lithium ion counterparts. However, their commercialization suffers from their low energy density and relatively short cycling life. Here, a porous carbon microsheets anode is produced by morphology‐preserved thermal transformation of sheet‐like manganese‐based metal–organic frameworks. The as‐produced porous carbon microsheets anode has a disordered, interlayer‐expanded, oxygen‐doped structure, which is demonstrated to have excellent K+ storage properties in terms of specific capacity, rate capability, and cycling stability. A PIC fabricated by employing Mn‐MOF derived porous carbon (MDPC) as the anode and activated carbon as the cathode, yields an energy density of up to 120 Wh kg−1 and a maximum power density of 26 kW kg−1 as well as a long‐term cycling life over 120 000 cycles, which is close to those of most Li‐ion counterparts. These promising results demonstrate that exploring novel carbon anodes can promote the rapid development of PICs toward practical applications. [ABSTRACT FROM AUTHOR]

Cell surface trafficking of many G protein‐coupled receptors is tightly regulated. Among them, the mandatory heterodimer GABAB receptor for the main inhibitory neurotransmitter, γ‐aminobutyric acid (GABA), is a model. In mammals, its cell surface trafficking is highly controlled by an endoplasmic reticulum retention signal in the C‐terminal intracellular region of the GB1 subunit that is masked through a coiled‐coil interaction with the GB2 subunit. Here, we investigate the molecular basis for the export of its homolog in Drosophila melanogaster that regulates the circadian rhythm and sleep. In contrast to mammals, the endoplasmic retention signal is carried by GB2, while GB1 reaches the cell surface alone. NMR analysis showed that the coiled‐coil domain that controls GABAB heterodimer formation is structurally conserved between flies and mammals, despite specific features. These findings show the adaptation of a similar quality control system during evolution for maintaining the subunit composition of a functional heterodimeric receptor. [ABSTRACT FROM AUTHOR]

SUMMARY: The root cell wall is the first and primary target of aluminum (Al) toxicity. Monocots such as rice (Oryza sativa) can accumulate appreciable levels of hydroxycinnamic acids (HCAs) to modify and cross‐link hemicellulose and/or lignin of the cell wall. Nevertheless, it is unclear whether this HCA‐mediated modification of the cell wall is important for Al accumulation and resistance. We previously isolated and characterized a rice ral1 (resistance to aluminum 1) mutant that shows enhanced Al resistance. In this study, we cloned RAL1 and found that it encodes the 4‐coumarate:coenzyme A ligase 4CL4, an enzyme putatively involved in lignin biosynthesis. Mutation of RAL1/4CL4 reduces lignin content and increases the accumulation of its substrates 4‐coumaric acid (PA) and ferulic acid (FA). We demonstrate that altered lignin accumulation is not required for the enhanced Al resistance in ral1/4cl4 mutants. We found that the increased accumulation of PA and FA can reduce Al binding to hemicellulose and consequently enhance Al resistance in ral1/4cl4 mutants. Al stress is able to trigger PA and FA accumulation, which is likely caused by the repression of the expression of RAL1/4CL4 and its homologous genes. Our results thus reveal that Al‐induced PA and FA accumulation is actively and positively involved in Al resistance in rice through the modification of the cell wall and thereby the reduced Al binding to the cell wall. Significance Statement: Monocots such as rice (Oryza sativa) can accumulate appreciable levels of 4‐coumaric acid (PA) and ferulic acid (FA) to modify the cell wall, but it is unclear whether PA and FA play a role in the resistance to aluminum (Al) stress. We demonstrate that Al stress can trigger the accumulation of PA and FA, which in turn modify hemicellulose to reduce Al binding to the cell wall and consequently increase Al resistance in rice. [ABSTRACT FROM AUTHOR]

To assess the homogeneity of and provide the first Sr‐Nd‐Hf‐Pb isotopic reference values for the Chinese Geological Standard Glasses CGSG‐1, CGSG‐2, CGSG‐4 and CGSG‐5, we measured these isotopes in several measurement sessions over the course of nearly 3 years. The results were obtained by high‐precision MC‐ICP‐MS and TIMS. Our investigation indicates that these CGSG glass reference materials are homogenous with regard to Sr‐Nd‐Hf‐Pb isotopic distribution and are therefore suitable geochemical materials for Sr‐Nd‐Hf‐Pb isotope measurements. Clear differences in Sr‐Nd‐Hf‐Pb isotopic composition were observed between the glasses and the original powdered rock reference materials (CGSG‐2 and GSR‐7, and especially CGSG‐5 and GSR‐2) because of flux addition during preparation of the glasses. The new Sr‐Nd‐Hf‐Pb isotope data provided here might be useful to the geochemical community for in situ and bulk analysis. [ABSTRACT FROM AUTHOR]

Follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) play critical roles in female reproduction, while the underlying genetic basis is poorly understood. Genome‐wide association studies (GWASs) of FSH and LH levels were conducted in 2590 Chinese females including 1882 polycystic ovary syndrome (PCOS) cases and 708 controls. GWAS for FSH level identified multiple variants at FSHR showing genome‐wide significance with the top variant (rs2300441) located in the intron of FSHR. The A allele of rs2300441 led to a reduced level of FSH in the PCOS group (β = −.43, P = 6.70 × 10−14) as well as in the control group (β = −.35, P = 6.52 × 10−4). In the combined sample, this association was enhanced after adjusting for the PCOS status (before: β = −.38, P = 1.77 × 10−13; after: β = −.42, P = 3.33 × 10−16), suggesting the genetic effect is independent of the PCOS status. The rs2300441 explained sevenfold higher proportion of the FSH variance than the total variance explained by the two previously reported FSHR missense variants (rs2300441 R2 = 1.40% vs rs6166 R2 = 0.17%, rs6165 R2 = 0.03%). GWAS for LH did not identify any genome‐wide significant associations. In conclusion, we identified genome‐wide significant association between variants in FSHR and circulating FSH first, with the top associated variant rs2300441 might be a primary contributor at the population level. [ABSTRACT FROM AUTHOR]