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Abstract Growth hormone secretagogue receptor 1a (GHS-R1a), also known as the ghrelin receptor, is an important nutrient sensor and metabolic regulator in both humans and rodents. Increased GHS-R1a expression is observed in the hippocampus of both Alzheimer’s disease (AD) patients and AD model mice. However, the causal relationship between GHS-R1a elevation in the hippocampus and AD memory deficits remains uncertain. Here, we find that increasing GHS-R1a expression in dCA1 pyramidal neurons impairs hippocampus-dependent memory formation, which is abolished by local administration of the endogenous antagonist LEAP2. GHS-R1a elevation in dCA1 pyramidal neurons suppresses excitability and blocks memory allocation in these neurons. Chemogenetic activation of those high GHS-R1a neurons during training rescues GHS-R1a overexpression-induced memory impairment. Moreover, we demonstrate that increasing GHS-R1a expression in dCA1 pyramidal neurons hampers these neurons’ ability to encode spatial memory and reduces engram size in the dCA1 region. Finally, we show that GHS-R1a deletion mitigates spatial memory deficits in APP/PS1 mice with increased GHS-R1a expression in the hippocampus. Our findings reveal a negative, causal relationship between hippocampal GHS-R1a expression and memory encoding, and suggest that blocking the abnormal increase in GHS-R1a activity/expression may be a promising approach to improve memory and treat cognitive decline in AD.

Abstract The current selection of ligands for both proteins of interest (POI) and E3 ubiquitin ligase significantly restricts the scope of targeted protein degradation (TPD) technologies. This study introduces cell-penetrating peptide-induced chimera conjugates (cp-PCCs) targeting the DHHC3 enzyme involved in PD-L1 palmitoylation. This approach disrupts PD-L1’s immunosuppressive function, enhancing anti-tumor immunity. We developed cp-PCCs to degrade DHHC3, directly linking DHHC3-mediated PD-L1 palmitoylation to PD-L1 stability on tumor cells. Our research utilized both in vitro assays and in vivo experiments in immune checkpoint blockade-resistant mouse models. We focused on a CRBN-based cp-PCC named PCC16, which demonstrated a DC50 of 102 nmol for DHHC3 degradation and significantly reduced PD-L1 levels. In resistant models, PCC16 not only robustly downregulated PD-L1 but also exhibited substantial anti-tumor activity in vivo without significant toxicity. This outperformed traditional inhibitors, showcasing the potential of cp-PCC technology to bypass current PROTAC limitations. Our findings suggest that cp-PCCs offer a promising method for targeting PD-L1 through DHHC3 inhibition and support their continued exploration as a versatile tool in cancer immunotherapy, especially for tumors resistant to standard treatments.

Abstract Background Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. Results Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequently activating fibroblasts and macrophages to promote RILI development. In response to IR, elevated TNKS1BP1 interacted with and decreased CNOT4 to suppress EEF2 degradation. Ectopic expression of EEF2 accelerated AECII senescence. Using a model system of TNKS1BP1 knockout (KO) mice, we demonstrated that TNKS1BP1 KO prevents IR-induced lung tissue senescence and RILI. Conclusions Notably, this study suggested that a regulatory mechanism of the TNKS1BP1/CNOT4/EEF2 axis in AECII senescence may be a potential strategy for RILI.

Abstract In this letter, the working mechanism of suggested bandpass filters with connected symmetric short‐circuit stub multimode resonators is described. Because of the design flexibility, the suggested bandpass filters' centre frequencies may be modified based on the design approach. Meanwhile, the suggested bandpass filters have reduced insertion losses and compact sizes. A prototype is built and tested with six passbands centred at 1.57/2.38/3.55/5.14/5.83/6.78 GHz to confirm the design and analysis. Good agreement between the simulated, and measured results is observed, indicating that the proposed structure can be applied in the field of communication, information, and automation.

Protein lysine crotonylation (Kcr) is one conserved form of posttranslational modifications of proteins, which plays an important role in a series of cellular physiological and pathological processes. Lysine ε-amino groups are the primary sites of such modification, resulting in four-carbon planar lysine crotonylation that is structurally and functionally distinct from the acetylation of these residues. High levels of Kcr modifications have been identified on both histone and non-histone proteins. The present review offers an update on the research progression regarding protein Kcr modifications in biomedical contexts and provides a discussion of the mechanisms whereby Kcr modification governs a range of biological processes. In addition, given the importance of protein Kcr modification in disease onset and progression, the potential viability of Kcr regulators as therapeutic targets is elucidated.

Abstract Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled‐coil domain containing 6 [CCDC6]‐rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N‐thy‐ori‐3‐1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low‐dose IR‐induced RET/PTC1 rearrangement in a dose‐dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI‐1, and Olaparib were employed to inhibit non‐homologous end joining (NHEJ), homologous recombination (HR), and microhomology‐mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR‐induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) decreased the efficiency of NHEJ and thus reduced IR‐induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR‐induced RET/PTC1 rearrangement. Targeting DNA‐PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR‐induced RET/PTC1 rearrangement in PTC.

In this study, comparative investigation on the effect of dry heating treatment (DHT) and annealing (ANN) on multi-structure, physicochemical properties and in vitro digestibility of black highland barley (BHB) starch was done. Results revealed that both DHT and ANN did not affect the “A”-type crystalline pattern and FT-IR spectroscopy of BHB starch, but changed the morphology, raised water absorption capacity and lowered viscosities. Compared to native starch, DHT- and ANN-modified samples had totally opposite alteration trends in amylose content, color characteristics, oil absorption capacity, gelatinization parameters and pasting temperature. These changes were positively related to treatment temperature and time for DHT-modified starches, while which were dependant on treatment duration for ANN-modified starches. Total in vitro hydrolysis rate and rapidly digestive starch content in starch markedly raised after DHT, whereas slowly digestive starch and RS levels decreased. Nevertheless, ANN significantly improved the hydrolyzation stability with treatment time prolonging, especially increased RS content and lowered RDS level. Therefore, this study identified both DHT and ANN were effective methods to alter the properties of BHB starch, and more importantly, they had distinguishing influence by different mechanisms, which would remind user to select appropriate means for physical starch modification based on different application purposes.

This paper undertakes an in-depth study and detailed analysis of the problem of the optimal selection of k leaders for a first-order leader-follower multi-agent system (MAS) whose interaction topology is an undirected graph, with the aim of achieving the maximum consensus convergence rate. The consensus performance of the MAS, which is characterized by the convergence rate, is associated with the algebraic connectivity, which is the smallest nonzero eigenvalue of the interaction topology. Firstly, with the increase in the distance between the followers and the leaders, the entries corresponding to the Fielder vector (the Laplacian eigenvector determined by the algebraic connectivity) also increases. Subsequently, the upper and lower bounds of the algebraic connectivity are obtained with the leader-induced diameter (LID) and the order of the graph. For an interaction topology of leader-follower MAS, it is shown through experiments on generated graphs that the algebraic connectivity has a negative correlation with the LID. Thus, the optimal k-leader selection problem can be approximately transformed into a metric k-center problem, i.e., select k-leader in an undirected graph so that the LID is minimum. Finally, the accuracy of the results was validated through experiments conducted on real networks.

Background: Anterior shoulder dislocation is the most common type of shoulder dislocation and is easy to develop into recurrent type, causing economic burden to society. This study uses the bibliometric method to analyze the global research status, hotspots and trends of anterior shoulder dislocation, aiming to promote the exploration of anterior shoulder dislocation. Methods: The literature on anterior shoulder dislocation in the past two decades were retrieved and downloaded from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and bibliometrix package of R software were used to conduct scientific bibliometric analysis of the literature. Finally, some statistical graphics were performed in Graphpad Prism. Results: A total of 3914 publications related to anterior shoulder dislocation from 2003 to 2022 were retrieved and screened from the WOSCC database. The ranking of the analysis results showed that Provencher MT was the author with the highest frequency of occurrence. Rush University was the most notable contributor. The American Journal of Sports Medicine was the most comprehensive journal. The United States was the most prominent country. Keywords related to surgical treatment were more significant than others. Conclusion: In the past two decades, the research output on anterior shoulder dislocation have been increasing year by year. The focus has gradually shifted to surgical treatment. Surgical treatment may continue to be the research hotspots in this field in the future.

Abstract Introduction Radiation‐induced pulmonary fibrosis (RIPF) is a chronic, progressive, irreversible lung interstitial disease that develops after radiotherapy. Although several previous studies have focused on the mechanism of epithelial–mesenchymal transition (EMT) in lung epithelial cells, the essential factors involved in this process remain poorly understood. The DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) exhibits strong repair capacity when cells undergo radiation‐induced damage; whether DNA‐PKcs regulates EMT during RIPF remains unclear. Objectives To investigate the role and molecular mechanism of DNA‐PKcs in RIPF and provide an important theoretical basis for utilising DNA‐PKcs‐targeted drugs for preventing RIPF. Methods DNA‐PKcs knockout (DPK−/−) mice were generated via the Cas9/sgRNA technique and subjected to whole chest ionizing radiation (IR) at a 20 Gy dose. Before whole chest IR, the mice were intragastrically administered the DNA‐PKcs‐targeted drug VND3207. Lung tissues were collected at 1 and 5 months after IR. Results The expression of DNA‐PKcs is low in pulmonary fibrosis (PF) patients. DNA‐PKcs deficiency significantly exacerbated RIPF by promoting EMT in lung epithelial cells. Mechanistically, DNA‐PKcs deletion by shRNA or inhibitor NU7441 maintained the protein stability of Twist1. Furthermore, AKT1 mediated the interaction between DNA‐PKcs and Twist1. High Twist1 expression and EMT‐associated changes caused by DNA‐PKcs deletion were blocked by insulin‐like growth factor‐1 (IGF‐1), an AKT1 agonist. The radioprotective drug VND3207 prevented IR‐induced EMT and alleviated RIPF in mice by stimulating the kinase activity of DNA‐PKcs. Conclusion Our study clarified the critical role and mechanism of DNA‐PKcs in RIPF and showed that it could be a potential target for preventing RIPF.

This study established a residue detection method based on the QuEChERS pre-treatment method and combined it with high-performance liquid chromatography–tandem mass spectrometry to test six herbicides (metamitron, clopyralid, desmedipham, phenmedipham, ethofumesate, and haloxyfop-p-methyl) in sugar beet plants, soil, and roots. The degradation dynamics and terminal residues of each herbicide in sugar beets were analysed. Finally, the dietary risks of various herbicides in sugar beets were evaluated based on the dietary structure of Chinese people, and the risk quotient values were below 100%. Using this detection method, all reagents exhibited good linearity (0.9724 ≤ R2 ≤ 0.9998), The limit of quantification (LOQ) ranged from 0.01 to 0.05 mg/L, the matrix effect ranged from −1.2% to −50%, the addition recovery rate ranged from 77.00% to 103.48%, and the relative standard deviation ranged from 1.61% to 16.17%; therefore, all indicators of this method met the residue detection standards. Under field conditions, the half-lives (t1/2) ranged about 0.65 ∼ 2.96 d and 0.38 ∼ 27.59 d in sugar beet plants and soil, respectively. All herbicides were easily degraded in sugar beet plants and soil (t1/2 < 30 d). The terminal residue amounts in the beet plants, soil, and roots ranged from < LOQ to 0.243 mg/kg. The dietary risk assessment of each pesticide was conducted based on the residual median of the terminal residues and the highest residual values on the edible part of the beetroot. The chronic exposure risk quotient (RQc) and acute exposure risk quotient (RQa) values were < 100%, indicating that the residue of each pesticide in beetroot posed low risks to consumers in China at the recommended dosage.

Abstract Background Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF. Methods Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague–Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18 F-labelled FAP inhibitor-42 ([18 F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively. Results RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [18 F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB. Conclusion RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [18 F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.

Based on the zero discharge and resource utilization of high-salt mine water, BP-A-C-BP three-chamber configuration bipolar membrane electrodialysis is used to treat high-salt mine water concentrate. Taking the high-salt mine water of a mine in Hebei as the raw water, after pretreatment + RO + decarburization + concentrated water RO + ED concentration, the final concentrate TDS reaches 93 040 mg/L, and the bipolar membrane electrodialysis test is carried out. The effects of current density, circulating flow rate and electrolyte concentration in the polar chamber on the acid and alkali production by bipolar membrane electrodialysis are investigated.The results show that in the current density range of 10-40 mA/cm2, with the increase of current density, the operating voltage increases, the current efficiency and capacity decrease gradually, and the energy consumption increases gradually. The optimal current density is 30 mA/cm2. When the circulating flow rate is in the range of 10-30 L/h, with the increase of the circulating flow rate, the current efficiency and production capacity increase, and the energy consumption decreases. Further increasing the circulating flow rate to 40 L/h will increase the energy consumption and reduce the production capacity. The optimal circulating flow rate is 30 L/h. The electrolyte concentration in the polar chamber should not be too low or too high, which is easy to increase energy consumption. The hydrolysis effect of bipolar membrane electrodialysis is the best when the concentration is moderate, and the optimal electrolyte concentration is 2%. The initial salt chamber concentrate of 4 L, the acid chamber and the alkali chamber are respectively 1.5 L deionized water and 2 L of 2% sodium sulfate in polar chamber. The current density is 30 mA/cm2, the circulating flow rate in polar chamber is 60 L/h, and the circulating flow rate in other chambers is 30 L/h. After 120 min of operation, the acid and alkali concentrations are 6.91% and 5.38%, respectively, which reach the expected target of the experiment. The current efficiency, productivity and energy consumption are 74.21%, 1.49 kg/(m2·h) and 1.66 kWh/kg, respectively. The acid and alkali solution produced by bipolar membrane electrodialysis process can be used in the zero discharge process of high-salt mine water and the downstream industrial chain of coal to realize the non-phase change resource of concentrated liquid. It avoids the problem of miscellaneous salt difficult to deal with, and also improves the economic value of wastewater.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver cancer with dismal outcome, high Ki-67 expression is associated with active progression and poor prognosis of iCCA, the application of MRE in the prediction of iCCA Ki-67 expression has not yet been investigated until now. We aimed to evaluate the value of magnetic resonance elastography (MRE) in assessing Ki-67 expression for iCCA. Results In the whole cohort, 97 patients (57 high Ki-67 and 40 low Ki-67; 58 males, 39 females; mean age, 58.89 years, ranges 36–70 years) were included. At the multivariate analysis, tumor stiffness (odds ratio (OR) = 1.669 [95% CI: 1.307–2.131], p

Abstract TAB182 participates in DNA damage repair and radio-/chemosensitivity regulation in various tumors, but its role in tumorigenesis and therapeutic resistance in breast cancer remains unclear. In the current paper, we observed that triple-negative Breast Cancer (TNBC), a highly aggressive type of breast cancer, exhibits a lower expression of TAB182. TAB182 knockdown stimulates the proliferation, migration, and invasion of TNBC cells. Our study first obtained RNA-seq data to explore the cellular functions mediated by TAB182 at the genome level in TNBC cells. A transcriptome analysis and in vitro experiments enabled us to identify that TAB182 downregulation drives the enhanced properties of cancer stem-like cells (CSCs) in TNBC cells. Furthermore, TAB182 deletion contributes to the resistance of cells to olaparib or cisplatin, which can be rescued by silencing GLI2, a gene downstream of cancer stemness-related signaling pathways. Our results reveal a novel function of TAB182 as a potential negative regulator of cancer stem-like properties and drug sensitivity in TNBC cells, suggesting that TAB182 may be a tumor suppressor gene and is associated with increased therapeutic benefits for TNBC patients.

Abstract Lack of proper innate sensing inside the tumor microenvironment could reduce both innate and adaptive immunity, which remains a critical cause of immunotherapy failure in various tumor treatments. Double-stranded DNA (dsDNA) has been evidenced to be a promising immunostimulatory agent to induce type I interferons (IFN-Is) production for innate immunity activation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, yet the unsatisfactory delivery and susceptibility to nuclease degradation hindered its feasibility for further clinical applications. Herein, we report on the constructed tumor microenvironment-responsive DNA-based nanomedicine loaded by dendritic mesoporous organosilica nanoparticles (DMONs), which provide efficient delivery of dsDNA to induce intratumoral IFN-Is production for triggering innate sensing for enhanced anti-tumor immunotherapy. Extensive in vitro and in vivo evaluations have demonstrated the dramatic IFN-Is production induced by dsDNA@DMONs in both immune cells and tumor cells, which facilitates dendritic cells (DCs) maturation and T cells activation for eliciting the potent innate immune and adaptive immune responses. Desirable biosafety and marked therapeutic efficacy with a tumor growth inhibition (TGI) of 51.0% on the murine B16-F10 melanoma model were achieved by the single agent dsDNA@DMONs. Moreover, dsDNA@DMONs combined with anti-PD-L1 antibody further enhanced the anti-tumor efficacy and led to almost complete tumor regression. Therefore, this work highlighted the immunostimulatory DNA-based nanomedicine as a promising strategy for overcoming the resistance to immunotherapy, by promoting the IFN-Is production for innate immunity activation and remodeling the tumor microenvironment. Graphical abstract

Objectives: To investigate the effect of different designs of movable parts and prosthetic materials on the stress distribution of supporting tissues in mandibular free end dentition defects using three-dimensional finite element analysis of digital Roach attachments. Material and methods: A 3D model of a patient with Kennedy class I mandibular edentulous conditions was generated, and twelve prosthesis models were applied, combining two designs of removable parts and six types of CAD/CAM restorative materials with different elastic modulus (conventional zirconia, ultra-translucent zirconia, Polyetheretherketone (PEEK), Lithium disilicate, Nanoceramic resin, and resin composite (Paradigm MZ100, 3 M ESPE)). The stress distribution of abutment periodontal ligament, edentulousmucosa, and junction of attachment were analyzed using finite element analysis. Results: The stress value of the buccal neck of the periodontal ligament and the maximum compressive stress of the distal periodontal ligament of the design with clasp arms were higher than those without clasp arms, while the stress on the junction of attachment and the displacement of the mucosa in the edentulous area were smaller. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended to be used as the fixed part of Roach attachment. Conclusion: CAD/CAM Roach attachments with clasp arms are recommended for the protection of mucosal soft tissue. Restorative materials with high elastic modulus, such as conventional zirconia and ultra-translucent zirconia, are recommended as the fixed part of Roach attachment for patients with free end defect of mandibular dentition. Clinical significance: This study provides references for the design with clasp arms and the selection of clinical fixed-movable prosthetic materials. Clinicians should consider the design of attachments and selection of appropriate manufacturing materials carefully to avoid negative impacts on patients' periodontal support tissues.

Abstract Background Alexithymia is common and causes serious harm to people living with HIV/AIDS. Therefore, this study aimed to examine its prevalence and associated factors among people living with HIV/AIDS in China. Methods A cross-sectional study was conducted in two designated AIDS medical institutions in Harbin, China between January and December 2019. In total, 767 participants completed the 20-item Toronto Alexithymia Scale, the University of California Los Angeles Loneliness short-form, the Patient Health Questionnaire-9, the HIV Treatment Regimen Fatigue Scale, and the Alcohol Use Disorders Identification Test‐Consumption. The participants responded to several questions regarding their demographic characteristics, life satisfaction, disease-related economic burden, and their antiretroviral therapy (ART) side effects. Multivariate logistic regression assessed the relationship between alexithymia and associated factors. Odds ratios (OR) and 95% confidence intervals (CI) for OR were calculated. Results Approximately 36.1% of the participants were classified as having alexithymia. After adjusted age and education, the logistic regression model indicated that disease-related economic burden (OR = 1.477, 95% CI = 1.155–1.888), ART side effects (OR = 1.249, 95% CI = 1.001–1.559), loneliness (OR = 1.166, 95% CI = 1.101–1.236), and HIV treatment regimen fatigue (OR = 1.028, 95% CI = 1.017–1.039) were positively associated with alexithymia. Conclusions The mental health problems of people living with HIV/AIDS are essential to understand and deserve attention. Disease-related economic burdens are major associated factors. Multiple actors should provide better services and guarantees for patients.

Abstract Over the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a ‘back to nature’ approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled.

Abstract Double‐strand break (DSB), a significant DNA damage brought on by ionizing radiation, acts as an initiating signal in tumor radiotherapy, causing cancer cells death. The two primary pathways for DNA DSB repair in mammalian cells are nonhomologous end joining (NHEJ) and homologous recombination (HR), which cooperate and compete with one another to achieve effective repair. The DSB repair mechanism depends on numerous regulatory variables. DSB recognition and the recruitment of DNA repair components, for instance, depend on the MRE11–RAD50–NBS1 (MRN) complex and the Ku70/80 heterodimer/DNA–PKcs (DNA–PK) complex, whose control is crucial in determining the DSB repair pathway choice and efficiency of HR and NHEJ. In‐depth elucidation on the DSB repair pathway's molecular mechanisms has greatly facilitated for creation of repair proteins or pathways‐specific inhibitors to advance precise cancer therapy and boost the effectiveness of cancer radiotherapy. The architectures, roles, molecular processes, and inhibitors of significant target proteins in the DSB repair pathways are reviewed in this article. The strategy and application in cancer therapy are also discussed based on the advancement of inhibitors targeted DSB damage response and repair proteins.

ObjectiveTo evaluate the effectiveness and safety of utilizing the small number of remaining vitrified oocytes after the failure of adequate fresh sibling oocytes. The outcome of present study would provide more comprehensive information about possible benefits or disadvantage to cryopreserve supernumerary oocytes for patients who have plenty oocytes retrieved.MethodsThis retrospective cohort study included 791 IVF/ICSI cycles using 6344 oocytes that had been vitrified in the Reproductive Hospital affiliated to Shandong University between January 2013 and December 2019.They were divided into three groups: SOC group (supernumerary oocytes cryopreservation), relative-MOC group (relative male factor-oocyte cryopreservation), and absolute-MOC group (absolute male factor-oocyte cryopreservation). Laboratory and clinical outcomes were analysed, and multivariate regression analysis was used to study the effect of different indications of vitrification on CLBR.ResultsThe CLBR was highest in absolute-MOC, and lowest in SOC (39.0% vs 28.9%, P=0.006); however, after adjusting for confounding factors, the difference was not statistically significant. Multivariable regression analysis showed no impact of indications of vitrified oocytes on CLBR according to controlled age, BMI, preservation duration, use of donor sperm or not, use of PESA/TESA or not, number of oocytes retrieved, number of oocytes thawed, and oocyte survival rate. The preliminary data of safety showed no significant differences in the perinatal and neonatal outcoms after ET and FET between the SOC and MOC groups.ConclusionDifferent indications of vitrification did not affect CLBR. The CLBR of vitrified oocytes for different indications was correlated with age and number of warmed oocytes. For women who have plenty oocytes retrieved, the strategy of cryopreserving a small number of oocytes is a valuable option and might benefit them in the future. Additional data from autologous oocyte vitrification research employing a large-scale and variable-controlled methodology with extending follow-up will complement and clarify the current results.

Abstract Background To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. Methods The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. Results The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600–0.748). Conclusions The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.

Dual active bridge (DAB) converters are extensively used due to the advantages of wide voltage regulation range and easy realization of soft switching. Besides, the concept of partial power converters (PPCs) has been widely applied to increase the converter efficiency by reducing the power actually processed by the converter. Therefore, in this article, the DAB converter and PPC are combined. And a high frequency DAB-based PPC aiming at efficiency optimization is selected out by analyzing and comparing the characteristics of several connections. Considering the wide voltage regulation range of DAB-based PPC, the extended-phase-shift-based control strategy aiming at zero-voltage switching (ZVS) range and current stress optimization is analyzed and adopted in this article. With the trend of high frequency for power converters, the non-ideal factors like output capacitors of switches need to be considered to improve the performance. The output capacitors are taken into consideration when analyzing the ZVS performance and the magnetizing inductor is utilized to expand ZVS range. To verify correctness of theoretical analysis, a prototype using GaN devices with 1 kW rated output power and 500 kHz switching frequency is built. The experimental results are consistent with the analysis.

As a fundamental branch in cross-modal retrieval, image-text retrieval is still a challenging problem largely due to the complementary and imbalanced relationship between different modalities. However, existing works have not effectively scanned and aligned the semantic units distributed in different granularities of images and texts. To address these issues, we propose a dual-branch foreground-background fusion network (FB-Net), which is implemented by fully exploring and fusing the complementarity in semantic units collected from the foreground and background areas of instances (e.g., images and texts). Firstly, to generate multi-granularity semantic units from images and texts, multi-scale semantic scanning is conducted on both foreground and background areas through multi-level overlapped sliding windows. Secondly, to align semantic units between images and texts, the stacked cross-attention mechanism is used to calculate the initial image-text similarity. Thirdly, to further adaptively optimize the image-text similarity, the dynamically self-adaptive weighted loss is designed. Finally, to perform the image-text retrieval, the similarities between multi-granularity foreground and background semantic units are fused to obtain the final image-text similarity. Experimental results show that our proposed FB-Net outperforms representative state-of-the-art methods for image-text retrieval, and ablation studies further verify the effectiveness of each component in FB-Net.

Summary: Background: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. Methods: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females). Using the closest gene to each IgE-associated CpG, we highlighted biologically plausible pathways underlying IgE regulation and analyzed the transcription patterns linked to IgE-associated CpGs (expression quantitative trait methylation loci; eQTMs). Using prior UK Biobank summary data from genome-wide association studies of asthma and allergy, we performed Mendelian randomization (MR) for causal inference testing using the IgE-associated CpGs from FHS with methylation quantitative trait loci (mQTLs) as instrumental variables. Findings: We identified 490 statistically significant differentially methylated CpGs associated with IgE in FHS, of which 193 (39.3%) replicated in CAMP and CRA (FDR < 0.05). Gene ontology analysis revealed enrichment in pathways related to transcription factor binding, asthma, and other immunological processes. eQTM analysis identified 124 cis-eQTMs for 106 expressed genes (FDR < 0.05). MR in combination with drug-target analysis revealed CTSB and USP20 as putatively causal regulators of IgE levels (Bonferroni adjusted P

Truncating mutations in filamin C (FLNC) are associated with dilated cardiomyopathy and arrhythmogenic cardiomyopathy. FLNC is an actin-binding protein and is known to interact with transmembrane and structural proteins; hence, the ablation of FLNC in cardiomyocytes is expected to dysregulate cell adhesion, cytoskeletal organization, sarcomere structural integrity, and likely nuclear function. Our previous study showed that the transcriptional profiles of FLNC homozygous deletions in human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are highly comparable to the transcriptome profiles of hiPSC-CMs from patients with FLNC truncating mutations. Therefore, in this study, we used CRISPR-Cas-engineered hiPSC-derived FLNC knockout cardiac myocytes as a model of FLNC cardiomyopathy to determine pathogenic mechanisms and to examine structural changes caused by FLNC deficiency. RNA sequencing data indicated the significant upregulation of focal adhesion signaling and the dysregulation of thin filament genes in FLNC-knockout (FLNCKO) hiPSC-CMs compared to isogenic hiPSC-CMs. Furthermore, our findings suggest that the complete loss of FLNC in cardiomyocytes led to cytoskeletal defects and the activation of focal adhesion kinase. Pharmacological inhibition of PDGFRA signaling using crenolanib (an FDA-approved drug) reduced focal adhesion kinase activation and partially normalized the focal adhesion signaling pathway. The findings from this study suggest the opportunity in repurposing FDA-approved drug as a therapeutic strategy to treat FLNC cardiomyopathy.

Abstract Polycystic ovary syndrome (PCOS) is associated with adverse pregnancy outcomes, including an increased risk of abortion, premature delivery, and even neonatal outcomes. After removing the effect of COH on patients, studying the pregnancy outcomes of patients with different PCOS phenotypes after FET may better reflect the impact of different PCOS phenotypes on ART outcomes. Data of 8903 patients who underwent FET between January 2017 and October 2019 were retrospectively collected and evaluated. All patients were divided into a control group and four phenotype groups based on Rotterdam criteria. The main outcomes were pregnancy outcomes after FET. We found significantly higher abortion (P = 0.010) and lower ongoing pregnancy (P = 0.023) rates for women with PCOS phenotypes A and D compared to those in the control group. After adjusting for potential confounders, PCOS phenotypes A and D were associated with an elevated risk of abortion (adjusted OR, 1.476, P = 0.016; adjusted OR, 1.348, P = 0.008, respectively). The results of this study suggest that when performing FET, clinicians should individually manage women with PCOS phenotypes A and D to reduce the rate of abortion and increase the rate of LB, and achieve better pregnancy outcomes.

The brain is the most advanced organ with various complex structural and functional microregions. It is often challenging to understand what and where the molecular events would occur for a given drug treatment in the brain. Herein, a temporo-spatial pharmacometabolomics method was proposed based on ambient mass spectrometry imaging and was applied to evaluate the microregional effect of olanzapine (OLZ) on brain tissue and demonstrate its effectiveness in characterizing the microregional pharmacokinetics and pharmacodynamics of OLZ for improved understanding of the molecular mechanism of drugs acting on the microregions of the brain. It accurately and simultaneously illustrated the levels dynamics and microregional distribution of various substances, including exogenous drugs and its metabolites, as well as endogenous functional metabolites from complicated brain tissue. The targeted imaging analysis of the prototype drug and its metabolites presented the absorption, distribution, metabolism, and excretion characteristics of the drug itself. Moreover, the endogenous functional metabolites were identified along with the associated therapeutic and adverse effects of the drug, which can reflect the pharmacodynamics effect on the microregional brain. Therefore, this method is significant in elucidating and understanding the molecular mechanism of central nervous system drugs at the temporo and spatial metabolic level of system biology.

Due to the interaction of many factors in the stock market, stock price prediction has always been a challenging problem in the field of machine learning. In particular, the mutation factors of the stock market often have a great impact on subsequent predictions. The existing prediction models seldom consider the impacts of other stocks in the stock market and mutation points on the prediction accuracy of target stocks. Therefore, this paper presents a new knowledge graph and deep learning method combined with a stock price prediction network focusing on related stocks and mutation points. First, the target stock price features are obtained through the ConvLSTM network. Second, the knowledge graph is used to mine the hidden relationships between stocks to find the stocks relevant to the target stock to obtain the market information vector and the market information features through the ConvLSTM network. Then, we find the mutation points according to the price change range, construct the mutation point distance weight matrix according to the distance from each trading day to the mutation points, and obtain the mutation point information features through the graph convolutional network (GCN). Finally, the features of market information, mutation point information and target stock price are fused to jointly predict the future stock price. The experimental results on the A share of Shenzhen from 2010 to 2019 show that the algorithm has good robustness and that the prediction accuracy is effectively improved.

As a physical method for starch modification, dry heating treatment (DHT) at high temperatures (150 and 180°C, respectively) was applied to blue highland barley (BH) starch with different durations (2 and 4 h). The effects on its multi-structures, physicochemical properties, and in vitro digestibility were investigated. The results showed that DHT had changed the morphology of BH starch, and the diffraction pattern remained an “A”-type crystalline structure. However, with an extension of DHT temperature and time, the amylose content, gelatinization temperature, enthalpy value, swelling power, and pasting viscosity of modified starches decreased, while the light transmittance, solubility, and water and oil absorption capacities increased. Additionally, compared with native starch, the content of rapidly digestible starch in modified samples increased after DHT, whereas those of slowly digestible starch and RS decreased. Based on these results, the conclusion could be drawn that DHT is an effective and green way to transform multi-structures, physicochemical properties, and in vitro digestibility of BH starch. This fundamental information might be meaningful to enrich the theoretical basis of physical modification on BH starch and extend the applications of BH in the food industry.

Abstract The working mechanism of suggested tunable bandstop filtered with asymmetrical multiple‐mode resonator equipped with tree‐shape branches is described in this letter. Because of the established degree of freedom, the suggested bandstop filters’ (BSFs) centre frequencies may be modified based on the design approach. Meanwhile, the suggested BSFs have small dimensions and abrupt roll‐off skirts for transition bands. A technology demonstration filter with six stopbands placed at 1.91/2.38/3.54/5.19/5.79/6.85 GHz was constructed to verify the design and analyses. It is found that the measurement of a filter is consistent with the comparison of simulation data, which indicates that the proposed structure is an optional approach for BSF design. The filter proposed can be applied in the field of communication, information and coal mine automation.

Abstract Background Hypertensive disorders of pregnancy (HDP) are an important cause of maternal and fetal mortality, and its potential risk factors are still being explored. Endometrial thickness (EMT), as one of the important monitoring indicators of endometrial receptivity, has been confirmed to be related to the incidence of HDP in fresh embryo transfer. Our study was designed to investigate whether endometrial thickness is associated with the risk of hypertensive disorders of pregnancy in frozen-thawed embryo transfer (FET). Methods This respective cohort study enrolled 13,458 women who received vitrified embryo transfer and had a singleton delivery in the Reproductive Hospital affiliated to Shandong University from January 2015 to December 2019. We set strict screening criteria and obtained the information from the hospital electronic medical system. Statistical methods including logistic regression analysis, receiver operating characteristic curve and restricted cubic spline were used to evaluate the relationship between endometrial thickness and the incidence of pregnancy-induced hypertension. Results The incidences of HDP in a thin endometrial thickness group ( 1.2 cm) were significantly greater than in a reference group (0.8 cm–1.2 cm) (7.98 and 5.24% vs 4.59%, P 1.2 cm) endometrial thickness achieve pregnancy through frozen-thawed embryo transfer.

Abstract Background Takeda G protein receptor 5 (TGR5) is widely recognized as a potential drug target for the treatment of metabolic diseases. TGR5 is not only a metabolic regulator, but also has a potential role that participating in developing and progressing of gastrointestinal cancer. We aimed to investigate the potential role of TGR5 in pancreatic cancer by utilizing molecular experiments and the liquid chromatography mass spectrometry (LC–MS) based metabolomics. Methods Herein, we assessed pancreatic cancer proliferation, migration and invasion in response to TGR5 antagonist SBI-115 in vitro experiments. Cell death was examined by using TUNEL assay on agarose-embedded sections. Then we investigated the effects of TGR5 on PANC-1 and BXPC3 cells via transmission electron microscopy (TEM). Moreover, LC–MS-based metabolomics was performed to explore the potential underlying mechanisms of TGR5 in pancreatic cancer. The correlations between TGR5 and the metabolism-related genes were further analysed by GEPIA 2 database. Results We found the proliferation capacities were decreased significantly in PANC-1 and BXPC3 cells after the treatment of SBI-115 for 48 h. The results of TUNEL assay showed that antagonism of TGR5 by SBI-115 had a remarkable effect on inducing cell death. Analysis of TEM demonstrated that SBI-115 treatment could impair the morphology of mitochondria in most PANC-1 and BXPC3 cells. The LC–MS-based analyses revealed that antagonism of TGR5 could alter the metabolic profiles of PANC-1 cells in vitro. Moreover, TGR5 was associated with some metabolism-related genes in pancreatic cancer. Conclusion Our data suggests that antagonism of TGR5 may suppress cell proliferation and induce apoptosis in pancreatic cancer cells. TGR5 may affect the metabolism of pancreatic cancer, and TGR5 would be an attractive target for pancreatic cancer treatment.

To investigate the influence of S. cerevisiae and L. plantarum co-fermentation on the storage characteristics of noodles. Texture analyzer (TA), low field pulsed nuclear magnetic resonance (LF-NMR) and X-ray diffraction (XRD) were used to analyze the quality changes of noodles during storage at 4 ℃. The main research results were as follows: The breakage rate and pH of fermented noodles were lower than these of blank group, there was no significant difference in water absorption rate among different samples(P>0.05), titratable acid (TTA) value increased with fermentation time prolonging. At the same storage time, the hardness and chewiness of the fermented noodles was lower than that of blank group. The cohesiveness decreased with time and was lower than that of blank group after 10~15 days storage. The elasticity first increased and then decreased during the storage duration. Compared with the blank group, the relaxation time of strongly bound water showed a descending trend. After stored at low temperature, the proportion of strongly bound water decreased. The X-ray diffraction pattern illustrated that the relative crystallinity (RC) of the blank group noodles was 16.77% after low temperature storage for 15 days, and the RC value of noodles fermented for 60 min was 12.10%, which was significantly lower than the blank group (P

Abstract In this letter, a novel sext‐band bandpass filter (BPF) using two split‐type multiple‐mode resonators is proposed. The filter is composed of two sets of resonators which are respectively designed to realize Filter 1 with two passbands and Filter 2 with quad passbands. Then the two BPFs are combined by parallel coupling feed lines for sext‐band responses, and each of the six centre frequencies in the proposed sext‐band BPF is able to be controlled due to the design freedom. To validate the design and analysis, a prototype filter has been fabricated with six passbands centred at 1.88/2.59/3.48/5.26/5.82/6.75 GHz. The measured result of the fabricated filter agrees well with the simulation, which shows that the proposed structure is a good candidate for sext‐band BPF designs and validates the proposed design flow well.

Exonuclease 1 (EXO1) can catalyze nucleotide chain excision with its conserved N-terminal domain of 5′ to 3′ exonuclease activity, enabling it to influence diverse biological processes facing the challenges of genotoxic environmental factors such as ionizing radiation. This nuclease activity enables EXO1 to maintain replication forks and telomeres length, to facilitate post-replication DNA repair and to process the end resection step of homologous recombination of DNA double-strand breaks-induced by ionizing radiation. When DNA replication is disrupted or blocked, EXO1 can cleave the broken DNA ends to form 3’ ssDNA, leading to repair pathways activation. Excess EXO1-mediated nucleotide excision, however, can introduce an abundance of single-stranded DNA that can cause mutation and recombination via micro-homology-mediated end joining or single-strand annealing mechanisms, contributing to a loss of genetic information. EXO1 activity must therefore be carefully regulated within healthy cells. The mutations and dysregulations of EXO1 can increase the sensitivity of cells to radiation injury and risk of oncogenic transformation, limit the adoption of specific treatments in a range of human diseases. As such, EXO1 represents a promising target for the treatment and prevention of cancer. In the present review, we delineate the structural properties and functional characteristics of EXO1, discuss the relationship between this exonuclease and cancer susceptibility as well as the second cancers related to radiotherapy.

In general, modified starches provided a desirable feature so that they can be used in the food industry like food additive products. The awareness of eating healthy has become very evident. The food industry is willing to produce foods and food ingredients that not only maintain nutrition but also promote health and safety. Tartary buckwheat starch has been isolated to assess the effect of HMT on its digestibility, morphological structure, pasting, thermal and textural properties and compared with common buckwheat, sorghum, and broomcorn millet. HMT changed significantly the granular structure of native starches. The complete starch granular structure increased the size and changed into an irregular shape, with a rough surface. The modified starches exhibited higher onset and peak temperatures, while their amylose content, solubility, swelling power, gel hardness, and enthalpy of gelatinization were significantly reduced. In pasting properties, tartary buckwheat and sorghum modified starch had the highest thermal treatment stability with lower setback and breakdown viscosity. Moreover, after three hours of starch hydrolysis; Resistant (RS) starch was higher in tartary buckwheat followed by broomcorn millet and lastly sorghum. In this study, we reported that tartary buckwheat modified starch is more useful in the preparation of food with thermal stability combined with a high amount of resistant starch.

ObjectiveOver the past decade, scarlet fever has caused a relatively high economic burden in various regions of China. Non-pharmaceutical interventions (NPIs) are necessary because of the absence of vaccines and specific drugs. This study aimed to characterize the demographics of patients with scarlet fever, describe its spatiotemporal distribution, and explore the impact of NPIs on the disease in the era of coronavirus disease 2019 (COVID-19) in China.MethodsUsing monthly scarlet fever data from January 2011 to December 2019, seasonal autoregressive integrated moving average (SARIMA), advanced innovation state-space modeling framework that combines Box-Cox transformations, Fourier series with time-varying coefficients, and autoregressive moving average error correction method (TBATS) models were developed to select the best model for comparing between the expected and actual incidence of scarlet fever in 2020. Interrupted time series analysis (ITSA) was used to explore whether NPIs have an effect on scarlet fever incidence, while the intervention effects of specific NPIs were explored using correlation analysis and ridge regression methods.ResultsFrom 2011 to 2017, the total number of scarlet fever cases was 400,691, with children aged 0–9 years being the main group affected. There were two annual incidence peaks (May to June and November to December). According to the best prediction model TBATS (0.002, {0, 0}, 0.801, {}), the number of scarlet fever cases was 72,148 and dual seasonality was no longer prominent. ITSA showed a significant effect of NPIs of a reduction in the number of scarlet fever episodes (β2 = −61526, P < 0.005), and the effect of canceling public events (c3) was the most significant (P = 0.0447).ConclusionsThe incidence of scarlet fever during COVID-19 was lower than expected, and the total incidence decreased by 80.74% in 2020. The results of this study indicate that strict NPIs may be of potential benefit in preventing scarlet fever occurrence, especially that related to public event cancellation. However, it is still important that vaccines and drugs are available in the future.

Ischemic stroke (IS) has been associated with an impairment in glymphatic function. Xuefu Zhuyu Decoction (XFZYD) is widely used in the prevention and treatment of ischemic stroke. We hypothesized that Xuefu Zhuyu decoction pretreatment could attenuate early neurological deficits after ischemic stroke by enhancing the function of the glymphatic system. To prove our hypothesis, we carried out temporary middle cerebral artery occlusion and reperfusion surgery on C57BL/6 mice and then measured neurological score, infarct size and performed hematoxylin-eosin staining to assess stroke outcomes after 24 h of reperfusion. Subsequently, we injected fluorescent tracers in to the cisterna magna and evaluated tracer distribution in coronal brain sections. The polarization of aquaporin-4 (AQP4), colocalization of aquaporin-4, α-dystroglycan, β-dystroglycan and agrin were determined by immunofluorescence. Our research showed that pretreatment with Xuefu Zhuyu decoction significantly alleviated neurological scores, neurological deficits and pathological abnormalities in a mouse model of ischemic stroke. Importantly, Xuefu Zhuyu decoction pretreatment enhanced cerebrospinal fluid influx, protected aquaporin-4 depolarization and promoted the colocalization of aquaporin-4 with its anchoring proteins in the brain. Our findings highlight novel mechanisms underlying the neuroprotective effect of Xuefu Zhuyu decoction pretreatment on ischemic stroke-induced brain damage through the glymphatic system. Xuefu Zhuyu decoction pretreatment may offer a promising approach to slow the onset and progression of ischemic stroke.

The present study aims to evaluate the effects of prepartum maternal supplementation of Capsicum oleoresin (CAP) on colostrum quality and growth performance in newborn buffalo calves. Twelve multiparous buffaloes were randomly assigned to two groups starting from 4 weeks prepartum: the control group with a basal diet (CON) and the treatment group with a basal diet supplemented with 20 mg CAP/kg dry matter (CAP20). After birth, all calves were weighed and received colostrum from their respective dam directly within 2 h. After that, calves received pasteurized milk and starter feed till 56 days of age. The results showed that CAP increased lactose (P < 0.05) in colostrum, and it tended to increase monounsaturated fatty acids; however, it decreased colostrum urea nitrogen (P < 0.10). CAP did not affect colostrum yield and immunoglobulin G and M concentrations. The weekly starter intake was not affected by maternal CAP supplementation during the first 6 weeks of life. There was an increasing tendency in weekly starter intake from weeks 7 and 8 (P < 0.10) in CAP20 compared with CON. At 7 days of age, calves in CAP20 had higher immunoglobulin G (P < 0.05) and a decreased tendency in calves' serum glucose compared with CON. Additionally, maternal CAP supplementation increased calves' serum β-hydroxybutyric acid (P < 0.05) and tended to increase total protein (P < 0.10), while decreased non-esterified fatty acids (P < 0.05) at 56 days of age. Calves in CAP20 had higher final withers height, final heart girth, average withers height, and average heart girth than the CON (P < 0.05). These results suggest that maternal CAP supplementation could improve colostrum quality and positively affect the performance of buffalo calves.

In the article, affine-periodic boundary value problem involving fractional derivative is considered. Existence of solutions to a Caputo-type fractional differential inclusion is researched by some fixed-point theorems and set-valued analysis theory. Specifically, we consider two cases in which the multifunction has convex values and nonconvex values, respectively.

Abstract Background The molecular mutations of the L1CAM gene and the imaging appearances of four fetuses with L1 syndrome from three independent Chinese families with a history of hydrocephalus were reported in this study. Two of the three are novel L1CAM variants. Methods Results of clinical and imaging examinations of three Chinese families were collected. Fetal samples were collected by puncture, genomic DNA was extracted, whole‐exome sequencing was performed, and the L1CAM gene mutation sites were verified by PCR and Sanger sequencing. Results In this case report, we described the imaging appearance and investigated the mutations of the L1CAM gene in three Chinese families with a history of L1 syndrome; these included two nonsense mutations (c.262C>T and c.261C>G) and one splice‐site mutation (c.524‐1G>A). Two of these three are novel L1CAM variants: c.262C>T and c.261C>G. The results of the sonographic images of the affected fetuses showed severe hydrocephalus. Bilateral lateral ventricles were dilated in the fetuses with c.262C>T and c.261C>G mutations. The left ventricle was about 14 mm wide and the right was about 14 mm in the fetus with c.262C>T mutation. The left ventricle was about 24.9 mm wide and the right was about 23.9 mm in the fetus with c.261C>G mutation. The ultrasound examination of the fetus with c.524‐1G>A mutation showed that the third ventricle (7.5 mm wide) was raised, and the fourth ventricle was communicated with the cisterna magna. The parents requested termination of the above pregnancy. Conclusion The current study emphasizes the importance of combining family history, prenatal ultrasonography, and L1CAM mutation testing positive for the diagnosis of the L1 syndrome.

This study aimed to determine the effect of capsicum oleoresin (CAP) on rumen fermentation and microbial abundance under different temperature and dietary conditions in vitro. The experimental design was arranged in a 2 × 2 × 3 factorial format together with two temperatures (normal: 39°C; hyperthermal: 42°C), two forage/concentrate ratios (30:70; 70:30), and two CAP concentrations in the incubation fluid at 20 and 200 mg/L with a control group. Regarding the fermentation characteristics, high temperature reduced short-chain fatty acids (SCFA) production except for molar percentages of butyrate while increasing acetate-to-propionate ratio and ammonia concentration. The diets increased total SCFA, propionate, and ammonia concentrations while decreasing acetate percentage and acetate-to-propionate ratio. CAP reduced acetate percentage and acetate-to-propionate ratio. Under hyperthermal condition, CAP could reduce acetate percentage and increase acetate-to-propionate ratio, lessening the negative effect of high heat on SCFA. Hyperthermal condition and diet altered the relative abundance of microbial abundance in cellulose-degrading bacteria. CAP showed little effect on the microbial abundance which only increased Butyrivibrio fibrisolvens. Thus, CAP could improve rumen fermentation under different conditions, with plasticity in response to the ramp of different temperature and dietary conditions, although hardly affecting rumen microbial abundance.

ObjectiveThis study aims to evaluate neonatal and children growth outcomes of cryotransfer of embryos developed from frozen gametes [double frozen transfer (DFT)].MethodsThis nested case-control study included 6,705 women who had a singleton live birth after embryo transfer at the Center for Reproductive Medicine, Shandong University, from 2008 to 2020. Of these, 745 women underwent frozen embryo transfer (FET) using embryos developed from frozen gametes (DFT). Propensity score methodology was used to balance the two groups by maternal age and body mass index (BMI) before evaluating outcomes. After age and BMI were matched using the propensity score methodology in a ratio of 1:4, the control groups enrolled 2,980 women who underwent fresh embryo transfer (ET) and 2,980 women underwent FET from fresh gametes. The children born were followed to at least 5 years of age, and some were followed up to 10 years. Neonatal outcomes and childhood growth measurements were compared among the three groups.ResultsThe average birth weight of the DFT group (3,462 g) was significantly higher than the FET group (3,458 g) and ET group (3,412 g). The rate of large for gestational age (LGA) babies in the DFT and FET group was higher than that for the ET group (30.9% vs. 24.8%; 29.4% vs. 24.8%, respectively). After adjusting for different confounder combinations in the three models, the birth weight and risk of LGA in the DFT and FET groups were still higher than in the ET group, and the values group of P for trend in the models were significant. In multiple linear regression analysis of the children’s development, the height Z-score of children born from the DFT and FET group was higher than that for children from the ET group (β = 0.21, 95% CI 0.07–0.35; b = 0.17, 95% CI 0.05–0.28, respectively). However, childhood growth measurements including body weight Z-score and BMI Z-score were not significantly different among the three groups. In addition, the proportion of male children born from DET was higher than that from ET.ConclusionsThere is an increased risk of LGA babies associated with pregnancies conceived from DFT. Children are inclined to be taller in the future in this group than after FET. The related etiology and pathophysiology mechanisms still need to be revealed. In the future, well-designed, observational studies with in-depth collection of patients’ characteristics may shed more light on this issue.

Abstract Background Thin endometrial thickness (EMT) has been suggested to be associated with reduced incidence of pregnancy rate after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment, but the effect of thin endometrium on obstetric outcome is less investigated. This study aims to determine whether EMT affects the incidence of obstetric complications in fresh IVF/ICSI-embryo transfer (ET) cycles. Methods We conducted a retrospective cohort study collecting a total of 9266 women who had singleton livebirths after fresh IVF/ICSI-ET treatment cycles at the Center for Reproductive Medicine Affiliated to Shandong University between January 2014 and December 2018. The women were divided into three groups according to the EMT: 544 women with an EMT ≤8 mm, 6234 with an EMT > 8–12 mm, and 2488 with an EMT > 12 mm. The primary outcomes were the incidence of obstetric complications including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), placental abruption, placenta previa, postpartum hemorrhage (PPH) and cesarean section. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between the EMT measured on the day of human chorionic gonadotropin (HCG) trigger and the risk of the outcomes of interest. Results The HDP incidence rate of pregnant women was highest in EMT ≤ 8 mm group and significantly higher than those in EMT from > 8–12 mm and EMT > 12 mm group, respectively (6.8% versus 3.6 and 3.5%, respectively; P = 0.001). After adjustment for confounding variables by multivariate logistic regression analysis, a thin EMT was still statistically significant associated with an increased risk of HDP. Compared with women with an EMT > 8–12 mm, women with an EMT ≤8 mm had an increased risk of HDP (aOR = 1.853, 95% CI 1.281–2.679, P = 0.001). Conclusion A thin endometrium (≤8 mm) was found to be associated with an increased risk of HDP after adjustment for confounding variables, indicating that the thin endometrium itself is a risk factor for HDP. Obstetricians should remain aware of the possibility of HDP when women with a thin EMT achieve pregnancy through fresh IVF/ICSI–ET treatment cycles.

Platinum nanoparticles (PtNPs) are classical peroxidase-like nanozyme; self-agglomeration of nanoparticles leads to the undesirable reduction in stability and catalytic activity. Herein, a hybrid peroxidase-like nanocatalyst consisting of PtNPs in situ growing on g–C3N4 nanosheets with enhanced peroxidase-mimic catalytic activity (PtNP@g–C3N4 nanosheets) was prepared for H2O2 and oxidase-based colorimetric assay. g–C3N4 nanosheets can be used as carriers to solve the problem of poor stability of PtNPs. We observed that the catalytic ability could be maintained for more than 90 days. PtNP@g–C3N4 nanosheets could quickly catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB), and the absorbance of blue color oxidized TMB (oxTMB) showed a robust linear relationship with the concentration of H2O2 (the detection limit (LOD): 3.33 μM). By utilizing H2O2 as a mediator, this strategy can be applied to oxidase-based biomolecules (glucose, organophosphorus, and so on, that generate or consume hydrogen peroxide) sensing. As a proof of concept, a sensitive assay of cholesterol that combined PtNP@g–C3N4 nanosheets with cholesterol oxidase (ChOx) cascade catalytic reaction was constructed with an LOD of 9.35 μM in a widespread range from 10 to 800 μM (R2 = 0.9981). In addition, we also verified its ability to detect cholesterol in fetal bovine serum. These results showed application prospect of PtNP@g–C3N4 nanosheets-based colorimetry in sensing and clinical medical detection.

Abstract Background Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare tumor. This study aimed to reveal the radiological characteristics of IPT-like FDCS by radiologic-pathologic correlation. Results We analyzed two cases of IPT-like FDCS in the liver, nine in the spleen, and two in both the liver and spleen concomitantly. IPT-like FDCS presented as well-defined iso- or hypodense masses on unenhanced computed tomography (CT) images in both the liver and spleen. Hyperintensities on T1-weighted images and hypointensities on T2-weighted images with hypointense rings were characteristic features in splenic cases. “Halo signs” were observed in two out of three liver tumors. Hepatic lesions showed significant enhancement, whereas splenic lesions showed only mild enhancement. Delayed annular enhancement was observed in both liver and spleen cases. On ultrasonographic examination, IPT-like FDCS presented as hypoechoic lesions with enhancement similar to that observed on CT. Hyaline fibrous pseudocapsules, which correlated with the hypointensities on T2-weighted images, were microscopically observed at the tumor edge. IPT-like FDCS was characterized by an abundance of small blood vessels and capillaries. Capillaries were also found in the fibrous capsule of some IPT-like FDCSs, which may explain the delayed annular enhancement. Conclusions The manifestations of IPT-like FDCS in the liver and spleen showed differences that warrant them to be approached differently during diagnosis. Characteristic radiological findings of IPT-like FDCS included different enhancement patterns between liver and spleen tumors and rim-like hypointensities on T2-weighted images, as well as annular enhancement on CT and magnetic resonance images. These imaging features correlated with tumor pathology.