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Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential. [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]

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]

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]

(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]

Anaplastic thyroid carcinoma (ATC) is the most advanced and aggressive thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) lacks anaplastic histology but has lost architectural and cytologic differentiation. Only a few studies have focused on the genetic relationship between the two advanced carcinomas and coexisting differentiated thyroid carcinomas (DTCs). In the present study, we investigated clinicopathologic features and genetic profiles in 57 ATC and PDTC samples, among which 33 cases had concomitant DTC components or DTC history. We performed immunohistochemistry for BRAF V600E, p53, and PD‐L1 expression, Sanger sequencing for TERT promoter and RAS mutations, and fluorescence in situ hybridization for ALK and RET rearrangements. We found that ATCs and PDTCs shared similar gene alterations to their coexisting DTCs, and most DTCs were aggressive subtypes harboring frequent TERT promoter mutations. A significantly higher proportion of ATCs expressed p53 and PD‐L1, and a lower proportion expressed PAX‐8 and TTF‐1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs. [ABSTRACT FROM AUTHOR]

Venous leg ulcer (VLU) is the most severe manifestations of chronic venous disease, which has characterized by slow healing and high recurrence rates. This typically recalcitrant and recurring condition significantly impairs quality of life, prevention of VLU recurrence is essential for helping to reduce the huge burden of patients and health resources, the purpose of this scoping review is to analyse and determine the intervention measures for preventing recurrence of the current reported, to better inform healthcare professionals and patients. The PubMed, Embase, Web of Science, Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wan Fang Data and Chongqing VIP Information (CQVIP) were accessed up to June 17, 2023. This scoping review followed the five‐steps framework described by Arksey and O'Malley and the PRISMA extension was used to report the review. Eleven articles were included with a total of 1503 patients, and adopted the four effective measures: compression therapy, physical activity, health education, and self‐care. To conclude, the use of high pressure compression treatment for life, supplementary exercise therapy, and strengthen health education to promote self‐care are recommended strategies of VLU prevention and recurrence. In addition, the importance of multi‐disciplinary teams to participate in the care of VLU in crucial. [ABSTRACT FROM AUTHOR]

BACKGROUND: Weeds are one of the critical factors that negatively affect crop yield and quality. Microbial herbicides are a research hotspot for novel herbicides owing to their environmental safety and lack of weed resistance. In the current study, the active ingredients of Serratia marcescens Ha1, a new microbial herbicide, were investigated for their effectiveness against agricultural weeds using bioassay‐guided fractionation. RESULTS: The results revealed that petroleum ether and ethyl acetate extracts of S. marcescens Ha1 had high herbicidal activity. Forty‐nine compounds were identified from the petroleum ether extract, including 2,4‐di‐tert‐butylphenol (DB; C14H22O, 38.82%), ethyl 14‐methyl‐hexadecanoate, 1‐nonadecene, and [1,1′‐biphenyl]‐2,3′‐diol, 3,4′,5,6′‐tetrakis. Of these, DB showed significant inhibitory effects on root and shoot growth in Amaranthus retroflexus, with half‐maximal inhibitory concentration (IC50) values of 389.17 and 832.44 mg L−1, respectively. In addition, 7‐hydroxy‐3‐(2‐methylpropyl)‐2,3,6,7,8,8a‐hexahydropyrrolo[1,2‐a]pyrazine‐1,4‐dione (HPD) was identified as the major active ingredient in the ethyl acetate extract of S. marcescens Ha1 using bioassay‐guided fractionation, with IC50 values of 439.86 and 476.95 mg L−1 against A. retroflexus shoot and root growth, respectively. Scanning electron microscopy indicated that DB and HPD exert destructive effects on A. retroflexus root, and the damage is gradually aggravated with increasing treatment time and concentration. CONCLUSION: The S. marcescens Ha1 extract and its active compounds DB and HPD exhibit significant herbicidal activity, which could be utilized further for the development of microbial herbicides. © 2023 Society of Chemical Industry. [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]

Development and regeneration in biological tissues are fundamentally affected by stem‐cell‐fate commitment. Bioelectricity is heterogeneous between different tissues and crucially regulates cell behaviors, including cell differentiation. However, the effects of heterogeneous bioelectricity on stem‐cell differentiation remain poorly understood. Herein, it is shown that providing stem cells with electrical stimulation matching the endogenous membrane potentials of cells derived from different tissues (osteogenic‐related: −55.05 ± 4.22 mV, neurogenic‐related: −84.8 ± 7.48 mV) can induce their osteogenic or neurogenic lineage commitment. Molecular dynamics simulations indicated that the osteogenic‐related surface potential favors the adsorption of fibronectin, while the neurogenic‐related surface potential enhances the adsorption of FGF‐2. These different protein adsorptions trigger either downstream Wnt or Erk signaling, which direct stem‐cell differentiation. Surface‐potential‐mediated lineage‐specification of stem cells using bioelectrical intensity has enormous potential application value in tissue regenerative therapy. [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]

A reaction of imidazo[1,2‐α]pyridine and Zhdankin reagent (IBA‐N3) is described for the synthesis of α‐iminonitriles via visible light photoredox catalysis. A series of substituted α‐iminonitriles were efficiently prepared in moderate to good yields under mild conditions. This transformation goes through a radical ring‐opening process to furnish the corresponding products. Notably, the reaction does not require toxic cyanide reagents, expensive metal photocatalysts and excessive oxidants. [ABSTRACT FROM AUTHOR]

For bone defect repair, it is critical to utilize biomaterials with pro‐angiogenic properties to enhance osteogenesis. Hydroxyapatite (HA)‐based materials widely used in clinical applications have shown much potential for bone repair. However, their predominant calcium phosphate (CaP) composition and poor biodegradability limit their angiogenic potential and hence osteogenic efficiency of HA‐based materials. Here, a magnesium ion‐doped calcium silicate/HA composite microscaffold (Mg‐CS/HA) is fabricated to enhance angiogenesis and osteogenic efficiency for bone repair. Incorporation of CS improved the biodegradability of the Mg‐CS/HA microscaffold, which could simultaneously release Si and Mg bioactive ions during the early stage of implantation, synergistically enhancing angiogenesis and osteogenic efficiency. In co‐culture systems, the synergistic effects of Si and Mg ions promote the "osteogenesis‐angiogenesis coupling effect." In vivo, the Mg‐CS/HA microscaffold could significantly promote reconstruction of the vascular network and bone regeneration. This study thus provides a new strategy for coordinated release of bioactive ions to achieve synergistic effects on vascularized bone regeneration by HA‐based bone implant materials. [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]

An impact reaction experiment is conducted with a modified split Hopkinson pressure bar (SHPB) apparatus to study the reaction threshold of aluminum/polytetrafluoroethylene (Al/PTFE) reactive materials under confining pressure. The dynamic compression behavior, impact damage characteristics, and impact reaction threshold of the Al/PTFE reactive material under the confining pressure are investigated. The results have presented that confining pressure makes the specimens suffer triaxial loading and improves the dynamic compressive strength of Al/PTFE reactive materials from 36.8 MPa (impact velocity is 14.64 m s−1) to 62.7 MPa (14.80 m s−1). Besides, the fractal dimension of the posttest specimen is decreased by confining pressure, which has proved that the confining pressure hinders damage under impact loading. Moreover, the impact reaction experiment demonstrates that the confining pressure increases the threshold of Al/PTFE, and the minimum specific incident energy for the reaction of the T10 (molding pressure is 10 MPa) specimen increases from 48.92 to 59.72 J cm−2. This research not only reveals that Al/PTFE can be reacted by impact loading at confining pressure but also clarifies that confining pressure limits the impact damage of the Al/PTFE reactive material and increases the reaction threshold. [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]

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]

This article presents a novel optimal constraint‐following controller for uncertain mechanical systems (MSs). The MS's uncertainty is unknown (possibly time‐varying) and bounded, but the bound is unspecified. Employing the frame of Udwadia–Kalaba theory, we design a robust controller with two tunable control gains for MSs, which guarantees some deterministic performances. Assuming the constraints to be holonomic and periodic, we transform the controlled MSs and introduce an iterative feedback tuning method for optimizing the proposed controller. After optimization, the final control scheme can achieve the equilibrium between the system performance and control cost for an arbitrary single constraint period. Simulations on a two‐link rotational manipulator are provided at last to demonstrate the proposed approach. [ABSTRACT FROM AUTHOR]

This article proposes a novel Nash game‐theoretical optimal adaptive robust control design approach to address the constraint‐following control problem for the uncertain underactuated mechanical systems with fuzzy evidence theory. First, the uncertainty is considered bounded and the bound is unknown but lies in a specified fuzzy evidence number. Second, a deterministic adaptive robust control scheme is proposed based on the servo constraint following control method, which renders the uncertain underactuated mechanical system to follow the specified constraints accurately with deterministic performance (guarantee uniform boundedness and uniform ultimate boundedness). It is shown that the designed self‐adjusting leakage‐type adaptive law can compensate for the uncertainty and avoid overcompensation. Third, based on the performance analysis and the fuzzy evidence description of uncertainty, the Nash game theory is introduced into the multi‐parameter optimization design for the two tunable control gains selected as two players. The cost functions for two players are relevant to the system constraint‐following performance and control cost. Then we can obtain the optimal control gains by seeking the Nash equilibrium which is always proved to exist. Ultimately, the simulation results on the two‐wheeled self‐balancing robot demonstrate the availability of the proposed control scheme and the optimal design approach for the underactuated mechanical systems with uncertainties. [ABSTRACT FROM AUTHOR]

Acquired immune deficiency syndrome (AIDS)‐related diffuse large B cell lymphoma (AR‐DLBCL) is a rare disease with a high risk of mortality. There is no specific prognostic model for patients with AR‐DLBCL. A total of 100 patients diagnosed with AR‐DLBCL were enrolled in our study. Clinical features and prognostic factors for overall survival (OS) and progression‐free survival (PFS) were evaluated by univariate and multivariate analyses. Central nervous system (CNS) involvement, opportunistic infection (OI) at lymphoma diagnosis, and elevated lactate dehydrogenase (LDH) were selected to construct the OS model; CNS involvement, OI at lymphoma diagnosis, elevated LDH, and over four chemotherapy cycles were selected to construct the PFS model. The area under the curve and C‐index of GZMU OS and PFS models were 0.786/0.712; 0.829/0.733, respectively. The models we constructed showed better risk stratification than International Prognostic Index (IPI), age‐adjusted IPI, and National Comprehensive Cancer Network‐IPI. Furthermore, in combined cohort, the Hosmer−Lemeshow test showed that the models were good fits (OS: p = 0.8244; PFS: p = 0.9968) and the decision curve analysis demonstrated a significantly better net benefit. The prognostic efficacy of the proposed models was validated independently and outperformed the currently available prognostic tools. These novel prognostic models will help to tackle a clinically relevant unmet need. [ABSTRACT FROM AUTHOR]

Summary: The compound eye system has many unique advantages, enabling organisms to quickly and accurately obtain the three‐dimensional spatial information of the target. Therefore, its bionic applications have great potential in object localization, dynamic tracking, and 3D reconstruction. However, the current bionic compound eye systems still have great difficulties in target detection. Most of the bionic compound eye systems only verify the possibility of three‐dimensional (3D) detection, and there is no suitable calibration and detection scheme. In this article, a fiber‐optic stereo bionic compound eye is designed, and a simple and rapid calibration method suitable for this system is selected by comparing two effective optical information. Further, the system quantitatively analyzes the detection performance of the target to achieve precise positioning and dynamic trajectory tracking. In the static detection experiment, the average detection errors of the 3D position at the horizontal angle, the elevation angle and the depth are 0.33°, 0.32° and 1.84 mm, respectively. In the dynamic trajectory tracking experiment, the circle radius errors in the X‐Z plane and Y‐Z plane are 0.04 and 2.20 mm, respectively. The proposed system provides a new perspective to understand the nature of the compound eye. [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]

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]

Laser energy is commonly used in tissue ablation, wound suturing, and other precise manipulations during surgery. However, currently available laser scanners require further improvements in terms of miniaturization, driving voltage, and stability to steer the laser beam accurately within a constrained environment. Herein, the development of a liquid‐driven laser scanner installed on the end effector of a continuum endoscope to perform fast and reliable laser steering is proposed. The developed laser scanner is 7 mm in diameter and 7 mm in length, and it is actuated with a voltage lower than 15 V due to the liquid‐infused membrane. The miniature size and low driving voltage of the proposed laser scanner facilitate safe laser‐assisted surgery in confined spaces. A theoretical model is established to predict laser spot position quantitatively, and laser steering ability is also tested experimentally. The fiber‐delivered laser beam can be steered for 21.2° (±10.6°) with a standard deviation of 0.3° in 1000 cycles, demonstrating excellent stability. A laser steering speed of up to 27.3 mm s−1 and a reflection loss of less than 3.1% are achieved. [ABSTRACT FROM AUTHOR]

This paper presents an optimal robust control for a permanent magnet synchronous motor (PMSM) with uncertainties and external disturbances which can be described by fuzzy approach. The fuzzy approach based on fuzzy set theory is distinguish from probability theory or fuzzy logic theory. Firstly, a dynamical model of the PMSM with uncertainties is established using a fuzzy approach. Then, a robust controller with an optimizable parameter is designed for PMSM to handle the uncertainties. The stability of the proposed control is proven using the Lyapunov theory. Furthermore, the controller gain is optimized by minimizing performance index, which contains the control performance and cost. Finally, the numerical simulations and experimental results are presented to validate the effectiveness of the proposed control with an optimal parameter. [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]

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]

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]

Melt electrospinning writing (MEW) has proven its potential to direct‐write complex and multiscaled architectures and structures, which are widely used in the biomedical fields such as 3D printing of porous scaffolds. For the resolution of the microstructure is characterized by the diameter of the melt electrospun fiber, uniform spinning fiber with predictable diameter is of great significance for precise fabrication of the microstructure. In this paper, the Kriging model was introduced to explore the scaling laws of the fiber diameter to several processing parameters (including temperature, tip‐to‐collector distance, flow rate, and collector speed). The Latin hypercube sampling was adopted for experiment design. The prediction results of the Kriging model were cross‐validated with the response surface model to compare the prediction accuracy of the two methods. The root‐mean‐square error, maximum absolute error, and mean absolute percentage error of the Kriging model (0.49%, 0.73%, and 3.52%, respectively) are all lower than the response surface model (0.81%, 1.25%, and 4.74%, respectively), indicating that the prediction accuracy of the Kriging model is superior to the response surface model. The present paper provides a new idea for the modeling of the complex nonlinear system of MEW. Moreover, the implementation of the Kriging model minimizes the number of experimental trials required from 31 to 27, resulting in the reduction of the fabrication time and materials wastage. [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]

Using renewable energy to convert CO2 into liquid products, as a sustainable way to produce fuels and chemicals, has attracted intense attention. Herein, a novel heterostructured photocathode composed of Si wafer, TiO2 layer, and Sn metal particles has been successfully fabricated by combining of a facile hydrothermal and electrodeposition method. The obtained Sn/TiO2/Si photocathode shows enhanced light absorption performance by the surface plasmon resonance effect of Sn metal. Especially, the Sn/TiO2/Si photocathode together with rich oxygen vacancy defects jointly promote photoelectrochemical CO2 reduction, harvesting a high faradaic efficiency of HCOOH and a desirable average current density (−4.72 mA cm−2) at −1.0 V vs. reversible hydrogen electrode. Significantly, the photocathode Sn/TiO2/Si also shows good stability due to the design of protecting layer TiO2. This study provides a facile strategy of constructing an efficient photocathode to improve the light absorption performance and the electron transfer efficiency, exhibiting great potential in the CO2 reduction. [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]

The epigenetic signature of cancer cells varies with disease progression and drug treatment, necessitating the study of these modifications with single cell resolution over time. The rapid detection and sorting of cells based on their underlying epigenetic modifications by flow cytometry can enable single cell measurement and tracking to understand tumor heterogeneity and progression warranting the development of a live‐cell compatible epigenome probes. In this work, we developed epigenetic probes based on bimolecular fluorescence complementation (BiFC) and demonstrated their capabilities in quantifying and sorting cells based on their epigenetic modification contents. The sorted cells are viable and exhibit distinctive responses to chemo‐therapy drugs. Notably, subpopulations of MCF7 cells with higher H3K9me3 levels are more likely to develop resistance to Doxorubicin. Subpopulations with higher 5mC levels, on the other hand, tend to be more responsive. Overall, we report for the first time, the application of novel split probes in flow cytometry application and elucidated the potential role of 5mC and H3K9me3 in determining drug responses. [ABSTRACT FROM AUTHOR]

The quasi‐two‐day waves (QTDWs) with westward‐propagating wavenumbers 2 (W2), 3 (W3), and 4 (W4) during the boreal summers were statistically examined using TIMED/SABER temperature observation datasets during 2002–2019 with a 6‐day two‐dimensional least‐squares fitting window. The W4 (W3) and W2 QTDWs were observed at ∼67–73 km and ∼30–40°N, and ∼89–95 km and ∼20–30°N, respectively. The W4 mode occurred 57 times over the past 18 years compared to 43 (52) times for the W3 (W2) QTDWs. The W4 QTDW reached maximum amplitudes of ∼9–10 K during 2006, 2009, and 2017, whereas W3 and W2 QTDWs attained maximum amplitudes of ∼8 K during 2017 and 2012. In addition, W4, W3, and W2 occurred more frequently with periods of 41–44 hr, 47–53 hr, and 44–50 hr, respectively. QTDW events with longer periods took place later than those events with shorter periods. Statistically, the W4 (W2) QTDW events were significantly more frequent during days 195–210 (165–180). In contrast, the W3 QTDW tended to occur during days 180–195 but was only slightly less frequent during days 195–210 and 210–225. Diagnostic analysis of the modern‐era retrospective analysis for research and applications ‐2 reanalysis dataset indicates that the attribution variations of the QTDWs, including their amplitudes and periods, were intimately related to the corresponding variabilities of the background zonal wind. Key Points: The W3 and W4 quasi‐two‐day waves (QTDWs) show clear amplitude and period variations in the middle atmosphere during the boreal summersThe W4 QTDW dominates the QTDW behaviors during boreal summers with the largest amplitude of ∼9–10 KThe periods of QTDWs are relatively stable during early and middle stages of the boreal summers but become longer during late boreal summers [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]