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Background: In the past, many meta-analyses (MAs) suggested that elemene injection (EI) played a complementary and alternative role in cancer treatment. However, some results were contradictory and a lot of evidences weren’t classified. Thus, their clinical guidance effect was very limited. Methods: Two reviewers independently retrieved 8 databases from their origin to May 19, 2023 and appropriate MAs were taken into consideration. A pooled analysis was conducted to merge results extracted from trials of included MAs. The methodological quality of MAs and the evidence certainty of pooled results were assessed. Results: 31 MAs were taken into analysis with poor methodological quality. The main weaknesses were in the areas of heterogeneity analysis, bias risk, and literature selection. According to the present evidence, on the one hand, compared with conventional treatment (CT) alone, EI combined with CT may significantly enhance short-term or long-term efficacy and reduce adverse reactions caused by CT in multiple cancers. On the other hand, using EI alone also can improve ORR in the malignant (pleural) effusion and lessen the recurrence rate in bladder cancer obviously with fewer adverse reactions compared with CT alone. However, this evidence was rated as moderate to very low certainty mainly due to the risk of bias in clinical trials. Conclusion: EI may be a viable medication for the treatment of cancer although more convincing trials are still required to demonstrate its alternative and complementary benefits. Besides, it seems to have a broad potential for further development in immunotherapy, drug delivery technique, and predictive factor.

Overall, China has made substantial progress in improving child survival over the past few decades, but a detailed understanding of child mortality trend at local level is limited. This study aimed to present a comprehensive analysis of under-5, infant, and neonatal mortality rates and its trend in Xicheng district of Beijing, China. We used the surveillance data of under-5 children reported by Preventive Health Department of Xicheng District Community Health Service Center from 1991 to 2022. The data was collected based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Data check was performed by each community health service center and related medical institutions. We extracted data included maternal age, date of death, date of birth, gender, census register, classification of any causes of death, and utilization of healthcare services before death and doubly input it in the Excel 2016 program. Categorization of the causes of death was adapted by the International Categorization of Diseases (ICD-10). Mortality rates and distribution of the leading causes of death were analyzed with descriptive statistics and the Pearson’s Chi-square test using SAS 14.0 software. The Chi-square trend test was used to explore the trends in mortality. Interrupted time series analysis (ITSA) was conducted to assess the impact of the two-child policy on mortality using STATA statistical packages. From 1991 to 2022, totally, there were 166,061 live births and 793 (4.78 ‰) under-5 deaths. The mortality rates of under-5 children, infants and neonates in Xicheng district decreased from 14.75 ‰, 11.25 ‰ and 8.00 ‰ to 1.03 ‰, 0.83 ‰ and 0.41 ‰ respectively. All mortality rates showed an overall significant decline trend (χ2 trend for neonatal = -15.8136, P trend for neonatal

Cellular protein detection is necessary for monitoring various biological pathways associated with complex diseases such as cancer. Detecting intracellular proteins is more challenging than cell surface protein detection because most antibodies cannot freely cross the cellular membrane. Cellular membrane permeabilization is thus required to facilitate the antibody diffusion and achieve adequate detection when combined with various conventional protein detection methods (e.g., flow cytometry and immunocytochemistry). However, these methods come with sensitivity challenges when a large number of cells are unavailable. Therefore, for early disease diagnostics and prognosis, novel methods are needed to achieve higher sensitivity to track disease-related proteins from small amounts of cells at early stages of disease progression. Here we applied a novel biosensing platform that co-entraps cells and gold nanoparticles in 3D hydrogel droplets to achieve sensitive fluorescence-based detection and quantification of intracellular proteins in intact cells. Importantly, intracellular metal enhanced fluorescence (iMEF) was achieved using gold nanoparticles via cell permeabilization. The intracellular gold-nanoparticles, together with the high cell loading capacity of the hydrogel droplets, enhanced the fluorescence signals and in turn improved assay sensitivity compared to conventional methods. After assay optimization, we demonstrated the detection of Heat Shock Protein 70, a common cancer marker, with as little as 250 cells. This technology was also able to distinguish between cancerous and non-cancerous samples when mimicking a clinical fine needle aspiration procedure. Compared to conventional assays measuring the same protein, the assay sensitivity was improved by two to three orders of magnitude, allowing for highly sensitive intracellular protein detection from minimal amounts of cells.

AbstractIntroduction To estimate the up-to-date prevalence of chronic kidney disease among the health check-up population in economically developed areas of China using estimated glomerular filtration rate, urinary albumin creatinine ratio, and kidney ultrasound.Methods Healthcare data from 38,093 subjects in 10 megalopolises of China who had an annual health check-up in 2021 were used. The overall and stratified prevalence of chronic kidney disease by sex, age, region and comorbidity group was reported. The association between chronic kidney disease and covariates of demographics, and comorbidities were analyzed in the multivariable-adjusted logistic regression model.Results A total of 3837 CKD cases were detected meeting any of the three CKD diagnostic criteria, with a crude prevalence of 10.1% in the study population. Using one criterion of decreased glomerular filtration rate, albuminuria and kidney structural abnormalities alone detected 204 (5.3%), 3289 (85.7%) and 563 (14.7%) cases, respectively. The addition of kidney ultrasound detected 427 (11.1%) structural abnormality cases without decreased GFR and albuminuria. The most common abnormalities were renal masses, hydronephrosis due to obstruction and congenital anomalies of kidney and urinary tract. Female, older age, low city-tier, hypertension, diabetes, obesity, hypertriglyceridemia as well as early disease stages such as pre-hypertension, impaired fasting glucose and overweight were significantly associated with chronic kidney disease.Conclusion Kidney ultrasound helps to amplify the detection of CKD patients, which is a supplement to kidney function and urine protein.

Acidic walnut green husk polysaccharide with weight average molecular weight of 5.101 kDa was isolated and designated WGHP-2, which was composed of galacturonic acid (69.47 %), galactose (11.18 %), rhamnose (8.67 %), arabinose (3.96 %), glucose (2.21 %), glucuronic acid (2.28 %), xylose (0.83 %), fucose (0.81 %) and mannose (0.59 %). The main glycosidic linkage types of WGHP-2 were → 4-α-D-Glcp-(1→, →4-α-D-GalpA-(1→, t-β-D-GlcpA-(1→, →2-β-D-Rhap-(1→, t-α-D-Galp-(1→, →4-α-D-Galp-(1 → and → 2,4)-α-D-Manp(1 →. Immunostimulating assays showed that WGHP-2 could significantly promote the proliferation of RAW264.7 cells, strengthen the phagocytic activity, and up-regulate the production and release of NO, ROS, TNF-α, INF-β and IL-6. Western-blot analysis indicated that MAPK and PI3K/Akt pathways were involved in the activation of macrophages induced by WGHP-2. Overall, our study suggests that WGHP-2 has the potential to be developed as a functional food with good immunostimulatory activity.

Exchange coupling interaction in sintered magnetic materials is generally isotropic. In this study, the anisotropic exchange coupling interaction was found in sintered oblate cylindrical SrFe12O19 (SrM) specimens obtained by the SrM nanopowders synthesized via a hydrothermal method. According to Henkel plots, the exchange coupling interaction between hard–hard magnetic grains was found in both as-pressed and sintered specimens. However, the exchange coupling interaction can only be found in the in-plane direction but not in the out-of-plane direction for the sintered specimens. By building a model of a grain configuration, this anisotropy of the exchange coupling interaction was ascribed to the vertically arranged plate-like SrM grains with micrometers in width but nanometers in thickness, which was confirmed by morphologies of cross sections in fractured specimens.

Objective To research the genetic polymorphism of HPA 1-6/10/15/21 in platelet donors in Zhongshan area, and establish a gene bank of platelet donors with HPA locus. Methods The HPA 1-6/10/15/21 system genotyping was performed by Real time fluorescent PCR combined with TaqMan probe technology on 192 platelet donors in Zhongshan area, and the genotype frequency and gene frequency were calculated. Results Only HPA-aa genotype was found within HPA-4/10, and no allele HPA-b had been detected. The majority of HPA-1, 2, 5, 6 and 21 genotypes were aa. HPA-3 and HPA-15 showed high heterozygosity, with genotype frequency of 0.307 3, 0.494 8 and 0.197 9 for HPA- 3aa, HPA-3ab and HPA-3bb, while 0.270 8, 0.505 2 and, 0.224 0 for HPA -15aa, HPA-15ab and HPA-15bb, respectively. Conclusion The distribution characteristics of HPA 1-6 /10/15/21 of platelet donors in Zhongshan shows regional differences compared with similar researches from other regions. The establishment of HPA gene bank is helpful to avoid alloimmunization caused by incompatible platelet transfusion.

Abstract Background Anesthesiologists need to appreciate the impact of preoperative anxiety in children. The present study aimed to explore whether interactive multimedia-based home-initiated interventions could effectively relieve preoperative anxiety in pediatric patients. Methods In this prospective study, we compared preoperative anxiety between two groups of children aged 4–9 years. Children in the control group received a question-and-answer (Q&A) introduction, and children in the intervention group received multimedia-based home-initiated preoperative education using comic booklets, videos, and coloring game books. Differences in anxiety between the two groups were evaluated by the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) at four time points: in the ophthalmology outpatient clinic before intervention as the baseline (T0); in the preoperative waiting area (T1); at the time of separating from their parents and moving to the operating room (T2); and at the time of anesthesia induction (T3). Parental anxiety was assessed by the Self-rating Anxiety Scale (SAS) and Visual Analog Scale (VAS) at T0 and T2. Other related information was collected by questionnaire. Results Eighty-four children who underwent pediatric strabismus in our center between November 2020 and July 2021 were included in this study. An intention-to-treat (ITT) analysis was performed on data from 78 enrolled children. Children in the intervention group exhibited lower m-YPAS-SF scores at T1, T2, and T3 than those in the control group (all p 4) was lower (2.6% vs. 17.5%, p = 0.048). The mean parental VAS score at T2 in the intervention group was significantly lower than that in the control group (p = 0.021). Conclusions Interactive multimedia-based home-initiated intervention could reduce preoperative anxiety in children and improve the quality of anesthesia induction based on ICC scores, which may in turn impose a positive impact on parental anxiety.

The enhancements in thermoelectric (TE) performances of p-type skutterudites are usually limited due to the relatively low Seebeck coefficients owing to the higher carrier concentration and more impurity phases induced by inherent structural instability of a Fe-based skutterudite. As shown in this study, alloying engineering of Ni doping at Fe sites in a p-type CeFe3.8Co0.2Sb12 skutterudite can not only reduce the impurity phases with high thermal conductivity but also regulate the carrier concentration, and thus significantly increase the Seebeck coefficient. The thermal conductivity was largely suppressed due to the enhanced point defect phonon scattering and decreased hole concentration. As a result, a TE figure of merit ZT of the CeFe3.5Ni0.3Co0.2Sb12 sample reached 0.8, which is approximately 50% higher than that of a Ni-free sample. Appropriate Ni doping can maintain a high ZT at a high temperature by controlling the reduction in a band gap. Therefore, a high average ZT close to 0.8 at 650–800 K for CeFe3.5Ni0.3Co0.2Sb12 was obtained, which was comparable to or even higher than those of the reported Ce-filled Fe-based skutterudites due to the synergistic optimization of electrical and thermal performances. This study provides a strategy to synergistically optimize electrical–thermal performances of the p-type skutterudites by alloying engineering.

The Atractylodes macrocephala Koidz. is a traditional Chinese rhizome herb, consumed for its well-known medicinal value. This review summarizes the recent research findings on biological activities, main biosynthesis pathways, PAO-ZHI processing, and technology application. The impact of biogeography led to significant differences in phenotypes and chemotypes. The PAO-ZHI processing also significantly affected A. macrocephala rhizome (AMR) bioactivity. A further systemic mechanistic investigation is required. Besides, new AMR polysaccharides with immunomodulatory effects, improving gastrointestinal function, and antitumor activity are constantly being isolated and characterized. Also, the discovery of novel families of compounds, such as the atractylenolides possessing antitumor, neuroprotective, immunomodulatory, and anti-inflammatory activities, is still ongoing work. Advanced genetics tools, such as in-depth transcriptomics, provide the basis for exploring A. macrocephala resources' functional genetic and molecular regulatory mechanisms. Still, some pathways are more elusive than others, and the biosynthetic pathways of sesquiterpenes, one of the prominent active families, still present a challenge in AMR and other plants. We propose here new directions and opportunities to advance current research in AMR. This review lays the theoretical foundation for fully developing and utilizing A. macrocephala resources.

Cancer: a drug combination for combating melanoma Drugs that target proteins involved in issuing stop and start commands to cancer-related genes help to sensitize melanoma cells to a widely used anti-cancer therapy, leading to tumor shrinkage in mice. Furong Zeng from Central South University in Changsha, China, and colleagues screened 240 approved anti-cancer agents in search of molecules that work synergistically with a BET inhibitor, an inhibitor of these proteins, to induce the death of melanoma cells. They found that a protein targeted by BET inhibitors (JQ1 and NHWD-870) regulates a growth factor protein, whose altered expression then helps to sensitize melanoma cells to sunitinib. Sunitinib is approved to treat several types of cancer and works by targeting many different kinds of kinase enzymes. The combination of BET inhibitors and sunitinib showed synergistic antitumor effects in a mouse model of melanoma.

The sustainable production of chemicals and fuels from waste carbon sources holds significant promise for reducing our dependence on fossil resources. Here, the authors demonstrate renewable formate production from biomass wastes and CO2 powered by solar energy.

Optimizing electrocatalytic activity and recognizing the most reactive sites for oxygen evolution reaction (OER) electrocatalysts are valuable to the order of renewable power. In this research article, we explored an innovative in-situ annealing technique for constructing iron carbide nanoparticles (Fe3C NPs) encapsulated via nitrogen and phosphorous doped bamboo-shape carbon nanotubes (NP-CNTs) for OER. Interestingly, the constructed Fe3C NPs@NP-CNT-800 composite exhibited remarkable electrochemical operation and offered a stable current density of 10 mA/cm2 at a lower overpotential (280 mV) in an alkaline solution. Furthermore, an innovative Fe3C NPs@N,P-CNT-800 hybrid surpassed the standard RuO2 electrocatalyst in terms of OER performance and showed negligible degradation in chronoamperometric (21 h) and chronopotentiometry (3000 cycles) analyses. The remarkable performance and stability are ascribed to the Fe3C NPs, novel tubular bamboo-like morphology of its carbon materials, and heteroatom doping, which contribute to the electrochemical interfaces, large surface area, active catalytic sites, and rapid charge transfer kinetics.

Abstract Background Growth-promoting antibiotics have been banned by law in the livestock and poultry breeding industry in many countries. Various alternatives to antibiotics have been investigated for using in livestock. Epimedium (EM) is an herb rich in flavonoids that has many beneficial effects on animals. Therefore, this study was planned to explore the potential of EM as a new alternative antibiotic product in animal feed. Methods A total of 720 1-day-old male broilers (Arbor Acres Plus) were randomly divided into six groups and fed basal diet (normal control; NC), basal diet supplemented with antibiotic (75 mg/kg chlortetracycline; CTC), and basal diet supplemented with 100, 200, 400 or 800 mg/kg EM extract for 6 weeks (EM100, EM200, EM400 and EM800 groups). The growth performance at weeks 3 and 6 was measured. Serum, intestinal tissue and feces were collected to assay for antioxidant indexes, intestinal permeability, lactic acid and short-chain fatty acids (SCFAs) profiles, microbial composition, and expression of intestinal barrier genes. Results The average daily feed intake in CTC group at 1–21 d was significantly higher than that in the NC group, and had no statistical difference with EM groups. Compared with NC group, average daily gain in CTC and EM200 groups increased significantly at 1–21 and 1–42 d. Compared with NC group, EM200 and EM400 groups had significantly decreased levels of lipopolysaccharide and D-lactic acid in serum throughout the study. The concentrations of lactic acid, acetic acid, propionic acid, butyric acid and SCFAs in feces of birds fed 200 mg/kg EM diet were significantly higher than those fed chlortetracycline. The dietary supplementation of chlortetracycline and 200 mg/kg EM significantly increased ileal expression of SOD1, Claudin-1 and ZO-1 genes. Dietary supplemented with 200 mg/kg EM increased the relative abundances of g_NK4A214_group and Lactobacillus in the jejunal, while the relative abundances of Microbacterium, Kitasatospora, Bacteroides in the jejunal and Gallibacterium in the ileum decreased. Conclusion Supplementation with 200 mg/kg EM extract improved the composition of intestinal microbiota by regulating the core bacterial genus Lactobacillus, and increased the concentration of beneficial metabolites lactic acid and SCFAs in the flora, thereby improving the antioxidant capacity and intestinal permeability, enhancing the function of tight junction proteins. These beneficial effects improved the growth performance of broilers. Graphical Abstract

Abstract There has been substantial research undertaken on the integration of computational thinking (CT) in K-12 mathematics education in recent years, particularly since 2018 when relevant systematic reviews were conducted on the topic. Many empirical studies in this area have yet to elaborate clearly and explicitly on how CT may support mathematics learning, or otherwise, in CT-based mathematics activities. Addressing this research gap, we conducted a systematic review on the integration of CT in K-12 mathematics education with a focus on CT-based mathematics instruction and students learning under such instruction. The Web of Science database was searched for in terms of studies published from 2006 to 2021, from which 24 articles were selected to provide illustrations of CT-based mathematics instruction and related student learning, and they were further analyzed according to education levels and contexts, programming tools, learning outcomes in CT and mathematics, and the mutual relationship between CT and mathematics learning. Among the results, this review found that geometrized programming and student-centered instructional approaches were facilitators of productive learning in CT and mathematics. Moreover, CT-based mathematics learning entails an interactive and cyclical process of reasoning mathematically and reasoning computationally, which can occur when: (1) applying mathematics to construct CT artefacts; (2) applying mathematics to anticipate and interpret CT outputs; and (3) generating new mathematical knowledge in parallel with the development of CT. The findings contribute to an in-depth understanding of what, and how, CT-based mathematics instruction impacts student learning in K-12 contexts.

Abstract Down syndrome (DS) is the most common chromosomal abnormality in live-born infants and is caused by trisomy of chromosome 21. Most individuals with DS display craniofacial dysmorphology, including reduced sizes of the skull, maxilla, and mandible. However, the underlying pathogenesis remains largely unknown. Since the craniofacial skeleton is mainly formed by the neural crest, whether neural crest developmental defects are involved in the craniofacial anomalies of individuals with DS needs to be investigated. Here, we successfully derived DS-specific human induced pluripotent stem cells (hiPSCs) using a Sendai virus vector. When DS-hiPSCs were induced to differentiate into the neural crest, we found that trisomy 21 (T21) did not influence cell proliferation or apoptosis. However, the migratory ability of differentiated cells was significantly compromised, thus resulting in a substantially lower number of postmigratory cranial neural crest stem cells (NCSCs) in the DS group than in the control group. We further discovered that the migration defects could be partially attributed to the triplication of the coxsackievirus and adenovirus receptor gene (CXADR; an adhesion protein) in the DS group cells, since knockdown of CXADR substantially recovered the cell migratory ability and generation of postmigratory NCSCs in the DS group. Thus, the migratory deficits of neural crest cells may be an underlying cause of craniofacial dysmorphology in individuals with DS, which may suggest potential targets for therapeutic intervention to ameliorate craniofacial or other neural crest-related anomalies in DS.

The isolation and purification, structure characterization and antioxidant activity of Zizyphus jujuba cv. Junzao polysaccharides were studied. The crude polysaccharide HZPC was extracted from Zizyphus jujuba cv. Junzao by water extraction and ethanol precipitation, and then separated and purified by DEAE-52 anionic chromatography column and Sephadex G-100 dexan gel column. The molecular weight and monosaccharide composition of HZPC-2 were determined by high performance gel chromatography (HPGPC) and ion chromatography (IC), and the structural characteristics of HZPC-2 were studied by ULTRAVIOLET spectrum, infrared spectrum and scanning electron microscope. Finally, the antioxidant activities of HZPC-2 were evaluated. The results showed that HZPC-2 polysaccharide was a neutral polysaccharide with α-glucopyranoside framework (JDP-N), its molecular weight was 3.25×104 Da. It was composed of rhamnose (Rha), arabinose (Ara), galactose (Gal), glucose (Glc), xylose (Xyl), mannose (Man) and galacturonic acid (GalA). The mole ratio was 0.05:0.34:0.29:0.15:0.08:0.02:0.06. Scanning electron microscopy showed that the surface of HZPC-2 was furry-shaped and extended in all directions, and the interior of HZPC-2 was embedded with porous structures. In vitro antioxidant tests showed that HZPC-2 had the strongest scavenging activity against DPPH radical, followed by hydroxyl radical, and the weakest scavenging activity against ABTS radical. It can be used as a potential antioxidant and provide a basis for the development of food with the function of Zizyphus jujuba cv. Junzao polysaccharides.

Objective Systematically evaluate the clinical efficacy of mifepristone combined with methotrexate therapy for ectopic pregnancy (EP), analyze the experimental designs, put forward improvement ideas.Methods RCTs of mifepristone combined with mifepristone for EP until January 2022 in six databases were searched. The primary outcome indicator was the cure rate. RevMan 5.4 was used to analyse and the online GRADEpro tool was used to assess the certainty of the evidence.Results Twenty-five RCTs involved 2263 patients. The cure rate was higher in the investigational group (OR = 4.09, 95%CI: [3.20, 5.22]), time of vagina stopped bleeding (MD = −11.21, 95%CI: [−11.85, −10.57]) and time of abdominal pain disappeared (MD = −6.24, 95%CI: [−6.63, −5.86]) were shorter in the investigational group, β-HCG level (MD = −585.32, 95%CI: [−609.62, −561.03]) was lower and diameter of the mass (MD = −1.23, 95%CI: [−1.40, −106]) was smaller in the investigational group. The certainty of the evidence for most outcomes was moderate or high, and only one was low.Conclusions The combination of mifepristone and methotrexate can improve the efficacy of ectopic pregnancy without amplifying the toxic side effects. Larger scale and better design of the randomized controlled trials are needed.KEY MESSAGESIn recent years, the increase in ectopic pregnancies and their impacts on female fertility makes physicians have to find an effective medical treatment as soon as possible that can avoid surgery.The mifepristone combined with methotrexate therapy for EP has better curative effects on improving the cure rate, lowering β-HCG level, reducing the mass, and alleviating symptoms of abdominal pain and bleeding, without amplifying the toxic side effects.Literature with high quality is lacking, and well-designed, large-scale and high-quality multicenter randomized controlled trials are needed.

Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomes and inhibiting protein synthesis. Nonetheless, its poor internalization ability to tumor cells has compromised the therapeutic promise of gelonin. In this study, a tumor acidity-responsive intracellular protein delivery system ─ functional gelonin (Trx-pHLIP-Gelonin, TpG) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP) and gelonin, was designed and obtained by genetic recombination technique for the first time. TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cell proliferation via triggering cell apoptosis and inhibiting protein synthesis. Most importantly, treatment by intravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much more effective than gelonin in curtailing tumor growth rates with negligible toxicity. Collectively, our present work suggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficient delivery of other bioactive substances to acidic diseased tissues.

Abstract The study is to evaluate the performance of ocular biometric measures and uncorrected visual acuity (UCVA) for detecting myopia among Chinese students. Among 5- to 18-year-old Chinese students from two cities of China, trained eye-care professionals performed assessment of ocular biometrics (axial length (AL), corneal curvature radius (CR), anterior chamber depth) under noncycloplegic conditions using NIDEK Optical Biometer AL-Scan, distance visual acuity using retro-illuminated logMAR chart with tumbling-E optotypes, and cycloplegic refractive error using NIDEK autorefractor with administration of 0.5% tropicamide. Spherical equivalent (SER) in diopters (D) was calculated as sphere plus half cylinder, and myopia was defined as SER ≤ − 0.5 D. Performances of ocular biometrics and UCVA (individually and in combination) for detecting myopia were evaluated using sensitivity and specificity, predictive values, and area under ROC curve (AUC) in both development dataset and validation dataset. Among 3436 students (mean age 9.7 years, 51% female), the mean (SD) cycloplegic SER was − 0.20 (2.18) D, and 1269 (36.9%) had myopia. Cycloplegic SER was significantly correlated with AL (Pearson Correlation coefficient r = − 0.82), AL/CR ratio (r = − 0.90), and UCVA (r = 0.79), but was not correlated with CR (r = 0.02, p = 0.15). The AL/CR ratio detected myopia with AUC 0.963 (95% CI 0.957–0.969) and combination with UCVA improved the AUC to 0.976 (95% CI 0.971–0.981). Using age-specific AL/CR cutoff (> 3.00 for age 3.06 for 10–14 years, > 3.08 for ≥ 15 years) as myopia positive, the sensitivity and specificity were 87.0% (95% CI 84.4–89.6%) and 87.8% (86.0–89.6%), respectively, in the development dataset and 86.4% (95% CI 83.7–89.1%) and 89.4% (95% CI 87.3–91.4%), respectively, in the validation dataset. Combining AL/CR and UCVA (worse than 20/32 for age

Peripheral nerve injury (PNI) is a structural event with harmful consequences worldwide. Due to the limited intrinsic regenerative capacity of the peripheral nerve in adults, neural restoration after PNI is difficult. Neurological remodeling has a crucial effect on the repair of the form and function during the regeneration of the peripheral nerve after the peripheral nerve is injured. Several studies have demonstrated that acupuncture is effective for PNI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve the nervous system remodeling in the process of nerve repair. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating related neurotrophins retrograde transport, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), N-cadherin, and MicroRNAs. Peripheral nerve injury enhances the perceptual response of the central nervous system to pain, causing central sensitization and accelerating neuronal cell apoptosis. Together with this, the remodeling of synaptic transmission function would worsen pain discomfort. Neuroimaging studies have shown remodeling changes in both gray and white matter after peripheral nerve injury. Acupuncture not only reverses the poor remodeling of the nervous system but also stimulates the release of neurotrophic substances such as nerve growth factors in the nervous system to ameliorate pain and promote the regeneration and repair of nerve fibers. In conclusion, the neurological remodeling at the peripheral and central levels in the process of acupuncture treatment accelerates nerve regeneration and repair. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of PNI.

IntroductionPhotoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations.MethodsWe established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein–protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug–gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsWe identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes.DiscussionOur findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

BackgroundPulmonary sclerosing pneumocytoma (PSP) is a rare lung tumor that is mostly isolated and commonly reported among middle-aged East Asian women. Recently, Immunohistochemistry (IHC) analysis has suggested that PSP is of primitive epithelial origin, most likely derived from type II alveolar air cells. Patients with PSP are generally asymptomatic and usually detected for other unrelated reasons during routine imaging. Several studies have already investigated the computed tomography (CT) features of PSP and their correlation with pathology. Magnetic resonance imaging (MRI) is a radiation-free imaging technique with important diagnostic value for specific pulmonary nodules. However, very few case reports or studies focus on the MRI findings of PSP.Case reportWe reported a case of an asymptomatic 56-year-old female with a solitary, well-defined soft-tissue mass in the lower lobe of the left lung. The mass showed iso-to-high signal intensity (SI) than muscle on T1-weighted image (T1WI) and T2-weighted image (T2WI) and a much higher SI on fat-suppressed T2WI, diffusion-weighted image, and apparent diffusion coefficient image. Contrast-enhanced fat-suppressed T1WI revealed noticeable inhomogeneous progressive enhancement throughout the mass. The mass revealed early enhancement without a significant peak, followed by a plateau pattern on dynamic contrast-enhanced MRI images. The patient underwent left basal segmentectomy via thoracoscopic surgery. Histopathology and IHC results of the surgical specimen confirmed that it was a PSP. We concluded that the MRI findings of PSP might adequately reflect the different components within the tumor and aid clinicians in preoperative diagnosis and assessment. To the best of our knowledge, this is the most comprehensive case report on the MRI findings of PSP.ConclusionThe MRI findings of PSP correspond to its histopathological features. Here, we present a case of PSP with the most comprehensive MRI findings, emphasizing the importance of multiple-sequence MRI in diagnosing PSP.

In order to accurately simulate the productivity variation characteristics of fractured wells with complex fracture network in shale gas reservoir, based on the multiple migration mechanism of shale gas, the micro-seismic data and discrete fracture model were used to characterize the fracture geometry and complex boundary characteristics, and the comprehensive seepage mathematical model of fractured wells with complex fracture network was established based on the dual porosity-discrete fracture model, and the numerical solution was carried out by combining the unstructured grid and the control volume finite element method. The sensitivity analysis of the influence of key parameters such as fracture conductivity, physical property difference in composite area and Langmuir volume on the production performance of fractured horizontal wells is carried out. This study provides theoretical methods and calculation tools for accurate prediction of productivity change and optimization of production system of fractured horizontal wells with complex fracture network in shale gas reservoirs.

The molecular mechanism of chromatin assembly factor 1 unit A (CHAF1A) promoting the proliferation and growth of epithelial ovarian cancer (EOC) cells hasn’t been reported at present. In this study, recombinant CHAF1A siRNA/overexpression plasmid (si-RNA1/pcDNA3.1-CHAF1A) was designed and constructed, and stable cell lines with knockdown or overexpression of CHAF1A were constructed. The changes of JAK2/STAT3 pathway were detected by Western blot. JAK2/STAT3 pathway was inhibited by Peficitinib, and then cell proliferation and growth ability were detected. Bioinformatics analysis suggested that CHAF1A was up-regulated in epithelial ovarian cancer. JAK2/STAT3 pathway phosphorylation was inhibited in si-RNA1 group, while it was increased in pcDNA3.1-CHAF1A group. After inhibiting JAK2/STAT3 pathway, the promoting effect of CHAF1A on epithelial ovarian cancer cell proliferation disappeared, meanwhile the inhibitory effect of CHAF1A on apoptosis enhanced. In conclusion, CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

The effects of different enclosure years on soil physicochemical properties provide scientific basis for soil fertility evaluation and ecological restoration. However, the details on the effects of long-term fencing measures on soil physicochemical properties in alpine regions are still lacking. The soil physicochemical properties, soil nutrient content, and stoichiometric characteristics of desert grassland were examined in the desert steppe of northern Tibetan Plateau, where grazing exclusion using fences has been implemented. This study included conducting experiments on different soil layers during different duration (10, 11, and 12 years) of grazing exclusion using fences; natural plots with no grazing exclusion were used as a control variable. Results showed that several soil physicochemical indexes, such as soil organic matter, soil water content, soil capillary porosity, soil non-capillary porosity, and soil capillary water capacity, in plots under the fencing measures were higher than those in the natural plots. The soil bulk density of the 12- and 11-year grazing exclusion plots was lower than that of the natural plots. The clay content of the 10- and 12-year grazing exclusion plots was higher than that of the natural plots, and the sand content was lower than that of the natural plots. The soil nutrient content was especially low with less than the average level of soil nutrient content in China. The stoichiometric C/N, C/P, N/P, and C/K ratios were 10.28–16.39, 2.74–16.69, 0.24–1.53, and 0.27–0.82, respectively. This result indicates that the degree of organic carbon mineralization was relatively high, and there existed a certain N limitation in the study area. The implementation of enclosure is conducive to the accumulation of C and N. The results provide support for elucidating the physicochemical characteristics, soil nutrients, and nutrient cycling of desert steppe in the northern Tibetan Plateau and for the study of the allotted time of fencing project in the alpine region.

Abstract Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small‐molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.

Astragali Radix (Huangqi) is mainly distributed in the Northern Hemisphere, South America, and Africa and rarely in North America and Oceania. It has long been used as an ethnomedicine in the Russian Federation, Mongolia, Korea, Kazakhstan, and China. It was first recorded in the Shennong Ben Cao Jing and includes the effects of reinforcing healthy qi, dispelling pathogenic factors, promoting diuresis, reducing swelling, activating blood circulation, and dredging collaterals. This review systematically summarizes the botanical characteristics, phytochemistry, traditional uses, pharmacology, and toxicology of Astragalus to explore the potential of Huangqi and expand its applications. Data were obtained from databases such as PubMed, CNKI, Wan Fang Data, Baidu Scholar, and Google Scholar. The collected material also includes classic works of Chinese herbal medicine, Chinese Pharmacopoeia, Chinese Medicine Dictionary, and PhD and Master’s theses. The pharmacological effects of the isoflavone fraction in Huangqi have been studied extensively; The pharmacological effects of Huangqi isoflavone are mainly reflected in its anti-inflammatory, anti-tumor, anti-oxidant, anti-allergic, and anti-diabetic properties and its ability to treat several related diseases. Additionally, the medicinal uses, chemical composition, pharmacological activity, toxicology, and quality control of Huangqi require further elucidation. Here, we provide a comprehensive review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of Astragalus to assist future innovative research and to identify and develop new drugs involving Huangqi.

ABSTRACT Haemophilus seminalis is a newly proposed species that is phylogenetically related to Haemophilus haemolyticus. The distribution of H. seminalis in the human population, its genomic diversity, and its pathogenic potential are still unclear. This study reports the finding of our comparative genomic analyses of four newly isolated Haemophilus strains (SZY H8, SZY H35, SZY H36, and SZY H68) from human sputum specimens (Guangzhou, China) along with the publicly available genomes of other phylogenetically related Haemophilus species. Based on pairwise comparisons of the 16S rRNA gene sequences, the four isolates showed 95% ANI values) with 17 strains that were previously identified as either “Haemophilus intermedius” or hemin (X-factor)-independent H. haemolyticus and therefore required a more detailed classification study. Phylogenetically, these isolates, along with the two previously described H. seminalis isolates (a total of 23 isolates), shared a highly homologous lineage that is distinct from the clades of the main H. haemolyticus and Haemophilus influenzae strains. These isolates present an open pangenome with multiple virulence genes. Notably, all 23 isolates have a functional heme biosynthesis pathway that is similar to that of Haemophilus parainfluenzae. The phenotype of hemin (X-factor) independence and the analysis of the ispD, pepG, and moeA genes can be used to distinguish these isolates from H. haemolyticus and H. influenzae. Based on the above findings, we propose a reclassification for all “H. intermedius” and two H. haemolyticus isolates belonging to H. seminalis with an emended description of H. seminalis. This study provides a more accurate identification of Haemophilus isolates for use in the clinical laboratory and a better understanding of the clinical significance and genetic diversity in human environments. IMPORTANCE As a versatile opportunistic pathogen, the accurate identification of Haemophilus species is a challenge in clinical practice. In this study, we characterized the phenotypic and genotypic features of four H. seminalis strains that were isolated from human sputum specimens and propose the “H. intermedius” and hemin (X-factor)-independent H. haemolyticus isolates as belonging to H. seminalis. The prediction of virulence-related genes indicates that H. seminalis isolates carry several virulence genes that are likely to play an important role in its pathogenicity. In addition, we depict that the genes ispD, pepG, and moeA can be used as biomarkers for distinguishing H. seminalis from H. haemolyticus and H. influenzae. Our findings provide some insights into the identification, epidemiology, genetic diversity, pathogenic potential, and antimicrobial resistance of the newly proposed H. seminalis.

Abstract Increased levels of circulating cell‐free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA‐associated diseases, but a nanomaterial‐based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol‐amine (PGA)‐covered MoS2 nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models. The nanosheets exhibit higher cfDNA binding capacity than polymer PGA and PGA‐based nanospheres owing to the flexibility and crimpability of their 2D backbone. Moreover, with low cytotoxicity and mild protein adsorption, the nanosheets effectively reduced serum cfDNA levels and predominantly accumulated in the kidneys to inhibit the formation of neutrophil extracellular traps and renal inflammation, thereby alleviating both lipopolysaccharide and ischemia‐reperfusion induced AKI in mice. Further, they decreased the serum cfDNA levels in samples from AKI patients. Thus, PGA‐covered MoS2 nanosheets can serve as a potent cfDNA scavenger for treating AKI and other cfDNA‐associated diseases. In addition, this work demonstrates the pivotal feature of a 2D sheet‐like structure in the development of the cfDNA scavenger, which can provide a new insight into the future design of nanoplatforms for modulating inflammation.

Sea cucumbers naturally prefer to inhabit crevices. Although this biological characteristic is widely used in sea cucumber aquaculture, the benefits of crevices remain largely unknown. The present study found that feeding and defecation rates significantly increased in sea cucumbers in the crevices for 24 h. After leaving the crevice, tentacle activity time of sea cucumbers in the experimental group was significantly more than that of those in the control group. Further, the present study found that sea cucumbers cultured in crevices for 21 days showed significantly longer adhesion time and tentacles activity time after air exposure and mechanical perturbation. Righting time of sea cucumbers cultured in crevices was significantly less than that in the control group after air exposure. In conclusion, the present study clarifies that crevice is beneficial to fitness-related behaviors of small A. japonicus. We consequently encourage aqua-farmers to increase the number of crevices in both pond culture and seed production, which is conducive to improve the feeding, defecation, adhesion, and righting behaviors of sea cucumbers.

The English grain aphid (EGA) (Sitobion avenae F.) is one of the most destructive species of aphids in wheat- (Triticum aestivum L.) planting areas worldwide. Large quantities of insecticides are usually used to control aphid damage. The identification of new EGA-resistant genes is necessary for sustainable wheat production. The objective of this study was to identify candidate genes for EGA resistance from stable quantitative trait loci (QTLs). We previously constructed a genetic map of unigenes (UG-Map) with 31,445 polymorphic sub-unigenes via the RNA sequencing of ‘TN18 × LM6’ recombinant inbred lines (TL-RILs). The relative aphid index (RAI) for the TL-RILs was investigated for two growing seasons, with three measured times (MTs) in each season. Using the UG-Map, 43 candidate genes were identified from 22 stable QTLs, with an average of 1.95 candidate genes per QTL. Among the 34 candidate genes annotated in the reference genome Chinese Spring (CS) RefSeq v1.1, the homologous genes of seven candidate genes, TraesCS1A02G-319900, TraesCS1B02G397300, TraesCS2D02G460800, TraesCS4A02G015600LC, TraesCS5B02G329200, TraesCS-6A02G000600 and TraesCS6A02G418600LC have been previously reported to play roles in aphid resistance. This suggests that these genes are strongly associated with EGA resistance in wheat. The candidate genes in this study should facilitate the cloning of EGA-resistant genes and genetic improvement in wheat breeding programs.

Clanis bilineata tsingtauica Mell (Lepidoptera: Sphingidae, CBT), as a traditional edible insect, is becoming popular in China due to its high nutritional value, but production needs to be improved to meet the expanding market. In the present study, CBT eggs were artificially inoculated on soybean leaves to evaluate the effects of leaf position, growth stage, sowing season, and soybean variety on CBT larval growth, respectively. The results showed that (1) the larval weight and survival rate were poorly correlated, so they could represent two different larval growth and development indicators for CBT. The 21-day-old larval weight was significantly different between the sowing seasons and between soybean growth stages, which was suitable as a key indicator for evaluating CBT larval rearing factors. (2) Compared with autumn-sown soybeans, the weight of 21-day-old larvae feeding on V6 stage (sixth trifoliolate) leaves of summer-sown soybeans was significantly higher, with an average increase of 44.7%. (3) Under autumn sowing conditions, the weight of 21-day-old larvae feeding on soybeans in the V6 stage was significantly higher than those fed on soybeans in the R3 stage (beginning pod), increasing by 33.9%. (4) Under summer sowing conditions, the weight of 21-day-old larvae feeding on the third-top leaf (the third leaf from the top of the soybeans’ main stem) was significantly higher than those feeding on the third-bottom leaf (the third leaf from the bottom of the soybeans’ main stem) at V6 stage by 35.7%. Similar results also appeared in autumn sowing; the average weights of 21-day-old larvae feeding on the third-top leaf increased significantly by 29.9% compared to those feeding on the third-bottom leaf. Moreover, the survival rate of larvae fed with the third-top leaf was significantly higher than that of those fed with the third-bottom leaf at the V6 stage in autumn sowing. Leaf position is the main factor affecting the survival rate of larvae. (5) Under summer sowing conditions, the weights of larvae fed with the third-top leaf of the susceptible-soybean varieties NN89-29 and NN1138-2 were significantly higher than that of those fed with the third-bottom leaf of these varieties. This difference was significantly reduced with autumn sowing. In conclusion, the CBT eggs inoculated on the third-top leaf of NN89-29 and NN1138-2 at the V6 stage in summer sowing could achieve maximum larval yield.

Little work seems to be known about stabilization results of highly nonlinear stochastic time-varying delay systems (STVDSs) with Markovian switching and Poisson jump. This paper is concerned with the stabilization problem for a class of STVDSs with Markovian switching and Poisson jump. The coefficients of such systems do not satisfy the conventional linear growth conditions, but are subject to high nonlinearity. The aim of this paper is to design a delay feedback controller to make an unstable highly nonlinear STVDSs with Markovian switching and Poisson jump $H_\infty$-stable and asymptotically stable. Besides, an illustrative example is provided to support the theoretical results.

ABSTRACTIt remains a challenge to achieve rapidly recoverable hydrogels by molecular hydrogen-bonding interaction because of its slow interaction kinetics. This work for the first time reports a trehalose (Tre)-based molecular movement mechanism inside a single network of polyacrylamide (PAM) that accelerates the kinetics of hydrogen-bonding interaction, and thereby endows the hydrogel with high toughness and rapid shape and mechanical recoverability. The resultant PAM@Tre hydrogel is capable of full shape recovery after 10,000 loading/unloading cycles at a strain of 500%. Even after being stretched at a strain of 2500%, it can recover to its original shape within 10 seconds. Moreover, the molecular movement of trehalose also endows the PAM@Tre hydrogel with fracture energy and toughness as high as ~9000 J m–2 and ~1600 kJ m–3, respectively, leading to strong resistance to both static and dynamic piercing. The PAM@Tre hydrogel is thus believed to have enormous potentials in protection devices, bionic skin, soft actuator, and stretchable electronics.

Rare earth (RE) can produce excellent precipitation hardening in Mg alloys. However, when forming a solid solution, it also deteriorates formability, a problem that can usually be overcome by raising deformation temperature. Here we report an unexpected observation of high temperature brittleness in a Mg-Gd-Y-Ag alloy. As the temperature reached 500 °C, the formability decreased drastically, leading to severe intergranular fracture under only 0.5% strain. This was caused by failure of grain boundaries, which are weakened by segregated interfacial compounds.

The polyphenol compounds in red jujube were extracted by ultrasonic-assisted extraction process. The methanol concentration, ultrasonic time, ultrasonic temperature and solid-liquid ratio were selected to conduct the single factor experiments. On this basis, the response surface methodology was used to optimize the process parameters, and the high-resolution liquid-mass spectrometer was used to determine the polyphenol components in red jujube to evaluate the antioxidant activity of the polyphenol based on its ability to remove DPPH and superoxide anion radicals. The results showed that, the optimal ultrasonic-assisted extraction conditions were as follows: Methanol concentration 70%, ultrasonic time 40 min, ultrasonic temperature 60℃, solid-liquid ratio 1:40 (g/mL). Under these conditions, the polyphenol yield was 1.397%±0.08%. A high-resolution liquid chromatography-mass spectrometry (HPLC-MS) method was developed for the determination of 19 components in jujube polyphenols, including phenolic acids and their derivatives, flavonoids and triterpenoids. The results of antioxidant experiments showed that the maximum clearance of DPPH was 77.63% when the polyphenol concentration of jujube was 0.3 mg/mL. The maximum clearance of superoxide anion radical was 82.48% when the concentration was 0.8 mg/mL, and with the increasing of polyphenol concentration, the clearance was close to VC, indicating that the polyphenol compound extracted from jujube had strong antioxidant activity and was a natural antioxidant with great development potential.

Potato virus Y (PVY) infection causes necrosis and curling of leaves, which seriously affect the yield and quality of Solanaceous crops. The roles of nutrient elements in the regulation of plant resistance to virus infection has been widely reported, while the mechanisms are poorly studied. Previous studies in our laboratory have demonstrated that foliar spraying of MgSO4 could induce Nicotiana tabacum resistance to PVY by increasing the activity of defense-related enzymes. Consistent with the results, we found that exogenous magnesium (Mg) had a certain effect on N. tabacum anti-PVY infection. Meanwhile, Illumina RNA sequencing revealed that Mg induced resistance to PVY infection was mainly by regulating carbohydrate metabolism and transportation, nitrogen metabolism, Ca2+ signal transduction and oxidative phosphorylation. Moreover, we used virus-induced gene silencing assays to verify the function of homologs of five N. tabacum genes involved in above pathways in N. benthamiana. The results showed that NbTPS and NbGBE were conducive to PVY infection, while NbPPases and NbNR were related to resistance to PVY infection. These results suggested a novel strategy for resistance to PVY infection and provided a theoretical basis for virus-resistance breeding.

IntroductionPlacental trophoblasts contribute to regulatory T (Treg) function via the programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway during normal pregnancy. Decreased expression of PD-L1 in trophoblasts was closely associated with Treg deficiency in the development of pregnancy failure. Thus, targeting PD-L1 might be a novel therapy to prevent pregnancy loss. However, the mechanisms for modulating the expression of PD-L1 in trophoblasts are an enigma.MethodsThe proportion of decidual Treg cells, and the profile of decidual macrophages (DMs) sampled from women with normal pregnancy (NP) and recurrent miscarriage (RM) were evaluated by flow cytometry. The expression of Yin and Yang 1 protein (YY1) and PD-L1 in human villous were measured by Immunohistochemistry (IHC), qRT-PCR and western blot. The determination of soluble PD-L1 (sPD-L1) in serum from NP and RM, and trophoblast conditioned media (TCM) was performed by the PD-L1 SimpleStep ELISA kit. Knockdown of YY1 was processed in the human trophoblast derived cell lines, HTR-8 and Bewo, with siYY1 transfection. Peripheral naïve CD4+ T cells were isolated from women with NP for the in vitro culture. The percentages of Treg cells differentiated from peripheral naïve CD4+ T cells were measured by flow cytometry. The interaction between YY1 and CD274 was proved by CHIP. The expression of inducible nitric oxide synthase (iNOS) in decidua was evaluated by IHC. The level of NO in serum from women with NP and RM was determined by the Griess reagent system. The effects of NO on YY1 were determined by the in vitro culture of HTR-8 cells with the NO donor, SNAP. The in vivo model comprising twelve pregnant mice and underwent different treatment. The percentages of Treg cells in murine uterus were measured by flow cytometry. Similarly, Western blot and IHC were performed to determine the expression of YY1 and PD-L1 in murine placenta.ResultsDecreased expression of YY1 and PD-L1 in trophoblasts and lower proportion of decidual Treg cells were observed in patients with RM. Knockdown of YY1 contributes to a lower expression of YY1 and PD-L1. Soluble PD-L1 in the supernatant from HTR-8 cells was also decreased with siYY1 administration. Lower Treg differentiation was observed in the presence of supernatant from HTR-8 cells treated with siYY1. CHIP analysis revealed that endogenous YY1 directly occupied the promoter region of the CD274 (PD-L1) gene. Accompanied with increased M1 DMs, higher NO was observed in serum sampled from patients with RM. In the presence of Reduced expression of YY1 and PD-L1 was observed in HTR-8 cells with the treatment of SNAP. Furthermore, less Treg differentiation was observed with SNAP treated TCM. Moreover, our in vivo data found that YY1 deficiency was associated with decreased PD-L1, which further resulting in less Treg differentiation and Treg deficiency at the maternal-fetal interface and increased embryo loss.DiscussionOur work found the modulatory capacity of YY1 on PD-L1 in trophoblasts during early pregnancy. Furthermore, reduced YY1 was supposed resulting from higher levels of NO produced from the M1 DMs in RM.

Abstract Introduction Labeling the emotional aspect of self‐unrelated stimuli (i.e., affect labeling) is a crucial strategy for implicit emotion regulation. However, it is uncertain whether affect labeling influences event‐related potential (ERP) responses (e.g., the late positive potential, LPP) to negative stimuli in comparison with control conditions in which attention is shifted to the emotional content of the stimuli (e.g., affect matching). Additionally, it is unknown whether affect labeling has a lasting effect on the processing of negative stimuli. Methods Participants were required to label the emotion (negative or neutral) of target pictures with two words, to match the emotion with alternative pictures or to merely view the target pictures. Target pictures were presented again immediately after the regulation task. After all the target pictures had been labeled, matched and viewed, the pictures were re‐exposed for the third time. Results The results showed that negative pictures elicited larger late LPP responses during the affect labeling task than during other tasks. However, the LPP responses were smaller for negative pictures in the affect labeling condition than in the other conditions when target pictures were re‐exposed immediately after the task. When target pictures were re‐presented again long after the regulation tasks, the LPP responses were smaller for negative stimuli with a history of affect labeling than viewing, whereas this effect did not differ between the affect labeling and matching conditions. Conclusion The current findings suggest that affect labeling has current effects and, to some extent, has lasting effects on negative stimulus processing.

Background This study assessed the quality distribution of non-mydriatic fundus photographs (NMFPs) in real-world glaucoma screening and analysed its influencing factors.Methods This cross-sectional study was conducted in primary healthcare centres in the Yinzhou District, China, from 17 March to 3 December 2021. The quality distribution of bilateral NMFPs was assessed by the Digital Reading Department of the Eye Hospital of Wenzhou Medical University. Generalised estimating equations and logistic regression models identified factors affecting image quality.Results A total of 17 232 photographs of 8616 subjects were assessed. Of these, 11.9% of images were reliable for the right eyes, while only 4.6% were reliable for the left eyes; 93.6% of images were readable in the right eyes, while 90.3% were readable in the left eyes. In adjusted models, older age was associated with decreased odds of image readability (adjusted OR (aOR)=1.07, 95% CI 1.06~1.08, p

Abstract As a kind of carcinoma with increasing morbidity, poor prognosis, and high mortality, esophageal squamous cell carcinoma (ESCC) is challenging for clinical management. Chemotherapy has been the standard treatment for ESCC over decades, while its clinical outcomes remain unsatisfying. And the regimen that combine standard chemotherapy with targeted therapy also demonstrates little effect. However, the advent of immune checkpoint inhibitors (ICI) proved to be a game changer in cancer treatment. Recent clinical trials had sprung up to evaluate the combined effect of ICI and chemotherapy regarding first‐line ESCC treatment. What's more, researchers attempt to explore the possibility to implement ICI monotherapy regarding second‐line ESCC treatment. In conclusion, most of the first‐line trails present inspiring achievement, while ICI monotherapy indicates little improvement for ESCC treatment. To point out the heterogenicity that could be the potential reasons biasing the pooled results, the differences of PD‐L1 immunohistochemistry (IHC) assays, geographic regions, chemotherapy regimens, and sex disparity among these trails are discussed respectively. In addition, the adverse events occurred during the trails are summarized, which confirm the safety of immunotherapy and chemoimmunotherapy. The article comprehensively reviews the representative explorations of using chemoimmunotherapy strategies in ESCC, as well as the deficiencies among them. Moreover, we highlight some feasible approaches. It will be beneficial for conducting more precise clinical trials on chemoimmunotherapy for ESCC in the future, including the use of more appropriate PD‐L1 IHC assays, careful consideration of the heterogeneity of the enrolled population and the optimal combination of chemotherapy and ICI.

Lipids in foods are sensitive to various environmental conditions. Under light or high temperatures, free radicals could be formed due to lipid oxidation, leading to the formation of unstable food system. Proteins are sensitive to free radicals, which could cause protein oxidation and aggregation. Protein aggregation significantly affects protein physicochemical characteristics and biological functions, such as digestibility, foaming characteristics, and bioavailability, further reducing the edible and storage quality of food. This review provided an overview of lipid oxidation in foods; its implications on protein oxidation; and the assessment methods of lipid oxidation, protein oxidation, and protein aggregation. Protein functions before and after aggregation in foods were compared, and a discussion for future research on lipid or protein oxidation in foods was presented.

Background: Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with late diagnosis; therefore, the identification of new early biomarkers could help reduce mortality. Efferocytosis, a process in which one cell engulfs another cell, including macrophages, dendritic cells, NK cells, etc., plays a complex role in tumorigenesis, sometimes promoting and sometimes inhibiting tumor development. However, the role of efferocytosis-related genes (ERGs) in HCC progression has been poorly studied, and their regulatory effects in HCC immunotherapy and drug targeting have not been reported.Methods: We downloaded efferocytosis-related genes from the Genecards database and screened for ERGs that showed significant expression changes between HCC and normal tissues and were associated with HCC prognosis. Machine learning algorithms were used to study prognostic gene features. CIBERSORT and pRRophetic R packages were used to evaluate the immune environment of HCC subtypes and predict treatment response. CCK-8 experiments conducted on HCC cells were used to assess the reliability of drug sensitivity prediction.Results: We constructed a prognostic prediction model composed of six genes, and the ROC curve showed good predictive accuracy of the risk model. In addition, two ERG-related subgroups in HCC showed significant differences in tumor immune landscape, immune response, and prognostic stratification. The CCK-8 experiment conducted on HCC cells confirmed the reliability of drug sensitivity prediction.Conclusion: Our study emphasizes the importance of efferocytosis in HCC progression. The risk model based on efferocytosis-related genes developed in our study provides a novel precision medicine approach for HCC patients, allowing clinicians to customize treatment plans based on unique patient characteristics. The results of our investigation carry noteworthy implications for the development of individualized treatment approaches involving immunotherapy and chemotherapy, thereby potentially facilitating the realization of personalized and more efficacious therapeutic interventions for HCC.

Objective: Fetomaternal hemorrhage (FMH) is an alloimmunization resulting caused by the incompatibility between fetal and maternal blood. For the prevention of newborn haemolytic disease (HDN), it is crucial to quantify the amount of fetomaternal hemorrhage. However, the classical Kleihauer–Betke test (K-B test) for detecting fetomaternal hemorrhage is limited by experimental tools and conditions and is not suitable for routine clinical use. Consequently, the method of prenatal diagnosis of fetomaternal hemorrhage applicable to the clinic is a topic worthy of further study. Therefore, it is worthwhile to further investigation on the clinically applicable prenatal diagnosis method for fetomaternal hemorrhage.Methods: This experiment demonstrates hydrogel’s ability to separate sensitized red blood cells from soluble antibodies. Using flow cytometry the fluorescence values of sensitized red blood cells and fluorophore-labeled antibodies were measured, and the testing steps for the detection products of a novel technology were determined. The properties of a hydrogel fluoroimmunoassay were evaluated by distinguishing between the amounts of fetal and adult haemoglobin. The precision of this technology is evaluated using the Kleihauer–Betke test as a comparison.Results: This experiment compared the detection of haemoglobin fluorescence in adults (n = 2) and fetuses (n = 6). At the same time, the fluorescence intensity of different fetal haemoglobin (HbF) in adult haemoglobin (HbA) was calculated. The fluorescence value is 1.6% when the fetal hemoglobin concentration is 0.1%.Conclusion: The novel hydrogel fluoroimmunoassay can accurately determine the fluorescence intensity by flow cytometry to differentiate fetal haemoglobin from adult haemoglobin, quantitatively prenatally diagnose fetal haemoglobin, address the incompatibility between fetal and maternal blood types, and prevent alloimmunization.