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Abstract Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive type of breast cancer with a poor prognosis and a high recurrence rate. Chemotherapy is still the mainstay of treatment for cancer patients without a genetic BRCA mutation, despite the approval of Olaparib, an inhibitor of the poly (ADP-ribose) polymerase (PARP) enzyme. Tripartite motif containing-21 (TRIM21) is one of the TRIM family members that has been investigated in various types of cancer. Here, we found that a low TRIM21 expression level was correlated with poor overall survival of TNBC patients. Knockout of TRIM21 promoted the proliferation of TNBC cells in vivo and in vitro, as well as migratory and invasive capabilities in vitro. Importantly, breast cancer susceptibility gene 1 (BRCA1) was identified as a ubiquitination substrate of TRIM21. It was confirmed that BRCA1 was upregulated after Olaparib treatment, which may explain the relative resistance of BRCA1-proficient TNBC cells to Olaparib. Moreover, Sorafenib, a standard treatment for hepatocellular carcinoma, increased the sensitivity of TNBC cells to Olaparib by promoting TRIM21-mediated ubiquitination degradation of BRCA1. Thus, a synergic effect of Olaparib and Sorafenib was found in vitro and in vivo. This combined treatment also aggravated DNA damage, cell cycle arrest, and apoptosis of TNBC cells. In summary, the findings verified the synergistic effect of Olaparib and Sorafenib and revealed TRIM21 as a potential target for TNBC therapy.

Postharvest ethylene accumulation and lignification are significant issues affecting the storage quality of fresh faba beans, resulting in rapid quality decline. However, there is still a lack of effective preservation methods to preserve the quality of faba beans during storage. This study aimed to investigate the regulation of lignification in faba beans during storage using a high-efficiency ethylene remover (HEER), examining physiological responses, key enzyme activities, and transcriptomic changes. Results showed that the HEER treatment inhibited the lignification, reducing it by 45% and lowering the respiratory rate of fresh pods by 32.8% during storage. Additionally, the HEER treatment suppressed respiration rates and the activities of lignin synthesis-related enzymes, including phenylalanine ammonia-lyase (from 353.73 to 246.60 U/g), cinnamic acid-4-hydroxylase (from 635.86 to 125.00 U/g), 4-coumarate: coenzyme A ligase (from 1008.57 to 516.52 U/g), and cinnamyl-alcohol dehydrogenase (from 129.42 to 37.12 U/g), thus slowing lignin accumulation. During storage, the hardness of fresh faba bean increased by 9.79% from the initial period, being 1.44 times higher than that of HEER. On days 8 and 16 of storage, the respiratory rate of the treated beans decreased by 24.38% and 4.12%, respectively. Physiological and enzyme activity analyses indicated that HEER treatment-induced increase in hardness was associated with the phenylpropanoid metabolic pathway. Moreover, the HEER significantly down-regulated the expression of several key genes, namely FaPAL, FaC4H, and FaCAD. This study helps to deepen the understanding of the inhibition of lignification by HEER and provide new insights for the development of preservation technology of faba bean.

We present a comprehensive investigation of mid-infrared (MIR) flux variability at 3.4 μm (W1 band) for a large sample of 3816 blazars, using Wide-field Infrared Survey Explorer (WISE) data through December 2022. The sample consists of 1740 flat-spectrum radio quasars (FSRQs), 1281 BL Lac objects (BL Lacs), and 795 blazars of uncertain type (BCUs). Considering Fermi Large Area Telescope detection, we classify 2331 as Fermi blazars and 1485 as non-Fermi blazars. Additionally, based on synchrotron peak frequency, the sample includes 2264 low-synchrotron peaked (LSP), 512 intermediate-synchrotron peaked (ISP), and 655 high-synchrotron peaked (HSP) sources. We conduct a comparative analysis of short- and long-term intrinsic variability amplitude (σm), duty cycle (DC), and ensemble structure function (ESF) across blazar subclasses. The median short-term σm values were 0.181−0.106+0.153, 0.104−0.054+0.101, 0.135−0.076+0.154, 0.173−0.097+0.158, 0.177−0.100+0.156, 0.096−0.050+0.109, and 0.106−0.058+0.100 mag for FSRQs, BL Lacs, Fermi blazars, non-Fermi blazars, LSPs, ISPs, and HSPs, respectively. The median DC values were 71.03−22.48+14.17, 64.02−22.86+16.97, 68.96−25.52+15.66, 69.40−22.17+14.42, 71.24−21.36+14.25, 63.03−33.19+16.93, and 64.63−24.26+15.88 percent for the same subclasses. The median long-term σm values were 0.137−0.105+0.408, 0.171−0.132+0.206, 0.282−0.184+0.332, 0.071−0.062+0.143, 0.218−0.174+0.386, 0.173−0.132+0.208, and 0.101−0.077+0.161 mag for the same subclasses, respectively. Our results reveal significant differences in 3.4 μm flux variability among these subclasses. FSRQs (LSPs) exhibit larger σm and DC values compared to BL Lacs (ISPs and HSPs). Fermi blazars display higher long-term σm but lower short-term σm relative to non-Fermi blazars, while DC distributions between the two groups are similar. ESF analysis further confirms the greater variability of FSRQs, LSPs, and Fermi blazars across a wide range of time scales compared to BL Lacs, ISPs/HSPs, and non-Fermi blazars. These findings highlight a close correlation between MIR variability and blazar properties, providing valuable insights into the underlying physical mechanisms responsible for their emission.

Diabetic peripheral neuropathy (DPN) is the most prevalent chronic complication among diabetic patients and a primary risk factor contributing to the deterioration of diabetic foot conditions. The pathogenesis of DPN remains complex and not fully understood, and there are hardly any effective treatment drugs. Maltol (3-hydroxy-2-methyl-4-pyranone) has demonstrated antioxidant and anti-inflammatory properties. However, the potential role of maltol in the treatment of DPN remains unclear. This study aimed to assess maltol’s effects on DPN rats and high glucose (HG)/palmitic acid (PA)-induced rat Schwann cells (RSC96). The results indicated maltol’s capacity to enhance peripheral nerve function in DPN rats. In RSC96 cells stimulated with high HG and PA, maltol treatment reduced DPN markers and apoptosis-related proteins. Functional enrichment analysis of differentially expressed genes revealed that endoplasmic reticulum (ER) stress pathways were involved in this process. Western blot results demonstrated the activation of ER stress pathway in HG/PA-induced RSC96 cells, with maltol attenuating ER stress-related protein expression. Furthermore, the knockdown of Membrane metallo-endopeptidase (MME) reversed maltol’s effects on apoptosis-related protein expression, suggesting a potential therapeutic role for maltol via MME in treating DPN. These findings indicate that maltol may hold promise as a therapeutic agent for DPN treatment.

Hepatocellular carcinoma (HCC) is a highly aggressive liver malignancy and one of the most lethal cancers globally, with limited effective therapeutic options. Bile acids (BAs), as primary metabolites of hepatic cholesterol, undergo enterohepatic circulation involving secretion into the intestine and reabsorption into the liver, and their composition is modulated in this process. Recent clinical observations have revealed a correlation between alteration in the BAs profile and HCC incidence, and the effect of various species of BAs on HCC development has been investigated. The regulatory effect of different BA species on cell proliferation, migration, and apoptosis in tumor cells, as well as their interaction with gut microbiota, inflammation, and immunity have been identified to be involved in HCC progression. In this review, we summarize the current understanding of the diverse functions of BAs in HCC pathogenesis and therapy, from elucidating the fundamental mechanisms underlying both tumor-promoting and tumor-suppressive consequences of various BA species to exploring potential strategies for leveraging BAs for HCC therapy. We also discuss ongoing efforts to target specific BA species in HCC treatment while highlighting new frontiers in BA biology that may inspire further exploration regarding their connection to HCC.

Background: There is currently no specific requirement for operator’s attires performing amniocentesis, especially for repetitive amniocenteses. We investigated the contamination status on the surface of operators with or without long-sleeved surgical gowns during repetitive amniocenteses to examine whether they are different. Methods: In a prospective cohort study, consecutive samples were collected from the surface of amniocentesis operators with short-sleeved scrubs (bare arms) or with long-sleeved surgical gowns on 4 sites (including the left and right proximal medial forearm, and the left and right ventral wrist). There were 7 time spots during each sampling period. Results: The highest colony count among all plates was 65 colony forming units (cfu)/plate. We observed 85.3% (382/448) and 65.1% (255/392) plates with 0 colony count from operators with bare arms and in surgical gowns, respectively. Moreover, the bacterial load of the group with surgical gowns had an increasing trend with time while the other group showed a contrary trend. Conclusions: All colony counts observed were within the hygiene specification of the National Health Commission of China. Instead of attires, other measures with high-quality evidence including surveillance of hand hygiene and control of indoor air bacterial load should be given more attention.

Phosphogypsum-based materials have gained much attention in the field of road infrastructure from the economic and sustainable perspectives. The Three-point bending test, the Four-point bending test and the Semi-circular bending test are three typical test methods applied for fracture energy measurement. However, the optimal test method for fracture energy evaluation has not been determined for phosphogypsum-based materials. To contribute to the gap, this study aims to analyze and compare the three test methods for fracture energy evaluation of phosphogypsum materials based on the peridynamic theory. For this purpose, the load–displacement, vertical displacement–Crack Mouth Opening Displacement (CMOD) and fracture energy of the phosphogypsum-based materials were measured and calculated from the three test methods. The simulated load–displacement and vertical displacement–CMOD by PD numerical models, with different fracture energy as inputs, were compared to the corresponding tested values according to simulation error results. The results showed that the Four-point bending test led to minimized errors lower than 0.189 and indicators lower than 0.124, demonstrating the most optimal test method for the fracture energy measurement of phosphogypsum-based material. The results of this study can provide new methodological references for the selection of material fracture energy measurement tests.

The desorption process of coal is interpreted from the perspective of thermodynamics. The four pending parameters of temperature-pressure-adsorption equation (TPAE) were obtained by using the measured series isothermal adsorption data of high-order structural coal and primary coal. The TPAE is transformed into an indefinite integral formula similar to the Clausius-Clapeyron equation, and an isosteric adsorption enthalpy is obtained. The product of the firmness coefficient and the desorption threshold is defined as the outburst threshold (OT), and is used to compare the difficulty of the coal and gas outburst between several types of coal. The results show that adsorption is a spontaneous heat release process, and desorption is not a spontaneous heat absorption process. The external energy required for desorption is equivalent to the threshold for desorption to occur. The desorption threshold (abbreviated as DT) is the unit isosteric desorption enthalpy. Through calculation, the occurrence of structural coal is 8.1 times more likely of coal and gas outburst than primary coal. The desorption rate of structural coal is no-linearly decreased with unit time. The greater the external energy, the faster the desorption rate decays. Blasting produces a large amount of external energy, immediately beyond the OT. It is, therefore, easier to induce coal and gas outburst.

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment.

Abstract Objective To report a rare gastroblastoma; discuss its clinical features, histopathological morphology, diagnosis, differential diagnosis, treatment, and prognosis; and so as to improve the understanding on this disease and provide reference for its diagnosis, treatment, and prognosis. Methods The diagnosis and treatment, imaging examination, pathological, and genetic data of a 19-year-old young female patient with gastroblastoma were analyzed retrospectively, and the relevant literature was reviewed and summarized. Results The patient was found to have a “gastrointestinal stromal tumor” for 3 days by physical examination in another hospital. Abdominal CT and MRI considered “solid pseudopapilloma of pancreas” and clinically planned to perform “radical pancreatoduodenectomy.” During the operation, the tumor was observed to bulge from the posterior wall of the gastric antrum, and the root was located in the gastric antrum, so it was changed to “partial gastrectomy + Ronx-y gastrojejunal anastomosis.” The postoperative pathology showed that the tumor was bi-differentiated between gastric epithelium and mesenchymal. Combined with the results of IHC and the opinions of several consultation units, the diagnosis of gastric blastoma (low-grade malignancy) was supported. However, the fracture rearrangement of GLI1 and EWSR1 genes was not detected by FISH. After 19 months of follow-up, no signs of tumor recurrence and metastasis were found. Conclusion Combined with existing literature reports, gastroblastoma occurs in young people, equally in men and women, and tends to occur in the gastric antrum. The biological behavior of the tumor tends to be inert, and the prognosis of most cases is good. Postoperative pathology and IHC are reliable methods for the diagnosis of gastric blastoma, and surgical resection of the lesion is the preferred treatment.

Lactate is an end product of glycolysis. Owing to the lactate shuttle concept introduced in the early 1980s, increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis. Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells, resulting in diverse biological consequences including decreased lipolysis, immune regulation, and anti-inflammation wound healing, and enhanced exercise performance in association with the gut microbiome. Furthermore, increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones, which accounts for its key role in immune modulation and maintenance of homeostasis. Here, we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.

Defined “industrial permeability VMD” as the permeable volume (m3) of unit membrane area (1000 m2) at unit time (1 day) and unit cross-membrane pressure difference (1 kPa). The VMD is directly calculated by using the daily computer’s records of Xi’an Siyuan A2/O-MBR system. After excluding five anomalies, 71% to 78% of effective industrial permeability was obtained from water yield and cross-membrane pressure difference of 3520 days original data. Each 25 effective industrial permeability was artificially divided into a group unit, and calculated the VMD arithmetic average of the group units. Then, group units are reduced into the annual units. A power equation is fitted into annual VMD arithmetic mean and annual units as the annual industrial permeability attenuation equation. The predicting value of industrial permeability is calculated by the previous attenuation equation, and the measuring value of industrial permeability is calculated by the present attenuation equation. The error ratio is defined as the relative size of the predicted and measured values. Calculating the annual industrial permeability attenuation is straightforward, simple, and convenient. It also show that the prediction period should not be less than three years, so it is best to choose four to five years.

Abstract Background It has been observed that Slo1 knockout mice have reduced motor function, and people with certain Slo1 mutations have movement problems, but there is no answer whether the movement disorder is caused by the loss of Slo1 in the nervous system, or skeletal muscle, or both. Here, to ascertain in which tissues Slo1 functions to regulate motor function and offer deeper insight in treating related movement disorder, we generated skeletal muscle‐specific Slo1 knockout mice, studied the functional changes in Slo1‐deficient skeletal muscle and explored the underlying mechanism. Methods We used skeletal muscle‐specific Slo1 knockout mice (Myf5‐Cre; Slo1flox/flox mice, called CKO) as in vivo models to examine the role of Slo1 in muscle growth and muscle regeneration. The forelimb grip strength test was used to assess skeletal muscle function and treadmill exhaustion test was used to test whole‐body endurance. Mouse primary myoblasts derived from CKO (myoblast/CKO) mice were used to extend the findings to in vitro effects on myoblast differentiation and fusion. Quantitative real‐time PCR, western blot and immunofluorescence approaches were used to analyse Slo1 expression during myoblast differentiation and muscle regeneration. To investigate the involvement of genes in the regulation of muscle dysfunction induced by Slo1 deletion, RNA‐seq analysis was performed in primary myoblasts. Immunoprecipitation and mass spectrometry were used to identify the protein interacting with Slo1. A dual‐luciferase reporter assay was used to identify whether Slo1 deletion affects NFAT activity. Results We found that the body weight and size of CKO mice were not significantly different from those of Slo1flox/flox mice (called WT). Deficiency of Slo1 in muscles leads to reduced endurance (~30% reduction, P

Abstract Background The study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD‐L1 expression in EGFR/ALK wild‐type lung adenocarcinoma patients eligible for ICI therapy. Methods In this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild‐type lung adenocarcinoma patients underwent comprehensive evaluations for PD‐L1 expression and NGS‐targeted sequencing. The investigation encompassed the analysis and comparison of clinical traits, gene mutations, pathways, and immune signatures between two groups categorized by PD‐L1 status: negative (TPS

ObjectiveFacioscapulohumeral muscular dystrophy type 1 (FSHD1) is one of the most common forms of autosomal-dominant muscular dystrophies characterized by variable disease penetrance due to shortened D4Z4 repeat units on 4q35. The molecular diagnosis of FSHD1 is usually made by Southern blotting, which is complex, time-consuming, and lacks clinical practicality. Therefore, in this study, optical genome mapping (OGM) is employed for the genetic diagnosis of FSHD1. Furthermore, epigenetic heterogeneity is determined from methylation analysis.MethodsGenomic DNA samples from four members of the same family were subjected to whole-exome sequencing. OGM was used to identify structural variations in D4Z4, while sodium bisulfite sequencing helped identify the methylation levels of CpG sites in a region located distally to the D4Z4 array. A multidisciplinary team collected the clinical data, and comprehensive family analyses aided in the assessment of phenotypes and genotypes.ResultsWhole-exome sequencing did not reveal variants related to clinical phenotypes in the patients. OGM showed that the proband was a compound heterozygote for the 4qA allele with four and eight D4Z4 repeat units, whereas the affected younger brother had only one 4qA allele with four D4Z4 repeat units. Both the proband and her younger brother were found to display asymmetric weakness predominantly involving the facial, shoulder girdle, and upper arm muscles, whereas the younger brother had more severe clinical symptoms. The proband's father, who was found to be normal after a neurological examination, also carried the 4qA allele with eight D4Z4 repeat units. The unaffected mother exhibited 49 D4Z4 repeat units of the 4qA allele and a minor mosaic pattern with four D4Z4 repeat units of the 4qA allele. Consequently, the presence of the 4qA allele in the four D4Z4 repeat units strongly pointed to the occurrence of maternal germline mosaicism. The CpG6 methylation levels were lower in symptomatic patients compared to those in the asymptomatic parents. The older sister had lower clinical scores and ACSS and higher CpG6 methylation levels than that of her younger brother.ConclusionsIn this study, two siblings with FSHD1 with phenotypically normal parents were identified by OGM. Our findings suggest that the 4qA allele of four D4Z4 repeats was inherited through maternal germline mosaicism. The clinical phenotype heterogeneity is influenced by the CpG6 methylation levels. The results of this study greatly aid in the molecular diagnosis of FSHD1 and in also understanding the clinical phenotypic variability underlying the disease.

Direct current triboelectric nanogenerators (DC-TENGs) are a groundbreaking technology to capture micromechanical energy from the natural environment, which is crucial for directly powering sensor networks. However, the research bottleneck in enhancing the triboelectric electrification capability and charge storage capability of dielectrics has hindered the overall performance breakthroughs of the DC-TENG. Here, a field emission model-based DC-TENG (FEM-TENG) is proposed, inspired by lightning rods. The enhanced local electric field between dielectric materials and electrodes induces strong electron tunneling, which improves charge neutralization on the surface of materials and their internal charge storage space, thereby utilizing the dielectric volume effect effectively and strengthening triboelectricity. Guided by the field emission model, the FEM-TENG with a historic crest factor of 1.00375 achieves a groundbreaking record of an average power density of 16.061 W m−2 Hz−1 (1,591 W m−3 Hz−1), which is 5.36-fold of the latest DC-TENG. In particular, the FEM-TENG with high durability (100%) truly realizes the collection of breeze energy and continuously drives 50 thermohygrometers. Four additional applications exemplify the FEM-TENG, enabling comprehensive sensing of land, water, and air. This work proposes a paradigm strategy for the in-depth utilization of dielectric films, aiming to enhance the output power of DC-TENGs.

The development of the textile and apparel (T&A) industry has led to an increasing focus on recycling used products. Remanufactured product quality raises consumer concerns, and blockchain can effectively solve this problem. We establish a closed-loop supply chain (CLSC) in which a manufacturer, a retailer, or a third-party recycler collects used T&A products to examine the most efficient recycling mode with and without blockchain and the impact of blockchain on CLSC decisions. The results show that (1) if the manufacturer’s recycling cost coefficient is relatively low, used T&A products are collected directly by the manufacturer. Otherwise, the responsibility for recycling used T&A products falls to the retailer or the third-party recycler. It is noteworthy that the manufacturer’s choice of recycling mode remains unchanged whether a blockchain is implemented or not. (2) The implementation of blockchain by the manufacturer and the retailer can increase profits and consumers also benefit when the cost of validating blockchain units remains below a certain threshold. (3) When the recycling cost coefficient exceeds a certain threshold, the implementation of blockchain increases prices and recycling rates. These findings offer CLSC members’ management insights into how to select the optimal recycling mode and the consequences of implementing blockchain.

Corporate social responsibility (CSR) is widely noticed as an essential tool for business operation and sustainable development. Meanwhile, the fiercely competitive external environment and unpredictable events prompt enterprises’ cooperation to prevent supply chain collapse. We investigate the cooperative strategy in a live-streaming supply chain (LSC) consisting of a dominant brand owner, a retailer, and a live streamer, where the brand owner considers CSR by considering the welfare of stakeholders. We construct one non-cooperative and three cooperative Stackelberg game models to explore the impact of CSR on cooperative strategy and LSC operations. The results show the following. (1) When the brand owner considers CSR, LSC members and systems are more profitable in the four models than when the brand owner does not consider CSR. (2) When the flow effect is small, the brand owner tends to cooperate with the retailer; otherwise, the brand owner prefers to cooperate with the live streamer. (3) The grand coalition C (the brand owner cooperates with the retailer and live streamer) is the consistent strategy for the LSC system, consumers, and society. These findings help enterprises recognize the importance of CSR and collaboration, thus further providing reference opinions on engaging in CSR and how to achieve collaboration.

The polymer desiccant cooling system (PDCS) efficiently reduces energy consumption compared to the vapor compression system (VCS). In this paper, a PDCS integrated heat pump is proposed. Experimental and simulation are used to analyze the performance of the PDCS. The control strategy is optimized with the NSGA Ⅱ algorithm. A case study in Shanghai illustrates the practical application of the PDCS optimization strategy. The calculation results based on the thermal comfort requirement show the maximum energy consumption of optimized PDCS, routine PDCS, and VCS are 549.9 kW, 597.7 kW, and 1327.7 kW. About 62.7 % and 72.3 % of energy can be saved in routine PDCS and optimized PDCS compared to VCS. Moreover, the maximum moisture removal efficiency of the above scenarios is 10.67 kW/(g·s), 11.56 kW/(g·s), and 25.42 kW/(g·s), separately. Additionally, the maximum coefficient of performance is 0.530, 0.457, and 0.182, respectively.

Abstract Background This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. Methods We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named “YOLO” to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). Results Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value

Abstract Background The Sinodielsia clade of the subfamily Apioideae (Apiacieae) was established in 2008, and it is composed of 37 species from 17 genera. Its circumscription is still poorly delimited and unstable, and interspecific relationships in the clade lack comprehensive analysis. Chloroplast (cp.) genomes provide valuable and informative data sources for evolutionary biology and have been widely used in studies on plant phylogeny. To infer the phylogenetic history of the Sinodielsia clade, we assembled complete cp. genomes of 39 species and then performed phylogenetic analysis based on these cp. genome sequence data combined with 66 published cp. genomes from 16 genera relative to the Sinodielsia clade. Results These 39 newly assembled genomes had a typical quadripartite structure with two inverted repeat regions (IRs: 17,599–31,486 bp) separated by a large single-copy region (LSC: 82,048–94,046 bp) and a small single-copy region (SSC: 16,343–17,917 bp). The phylogenetic analysis showed that 19 species were clustered into the Sinodielsia clade, and they were divided into two subclades. Six mutation hotspot regions were detected from the whole cp. genomes among the Sinodielsia clade, namely, rbcL–accD, ycf4–cemA, petA–psbJ, ycf1–ndhF, ndhF–rpl32 and ycf1, and it was found that ndhF–rpl32 and ycf1 were highly variable in the 105 sampled cp. genomes. Conclusion The Sinodielsia clade was subdivided into two subclades relevant to geographical distributions, except for cultivated and introduced species. Six mutation hotspot regions, especially ndhF–rpl32 and ycf1, could be used as potential DNA markers in the identification and phylogenetic analyses of the Sinodielsia clade and Apioideae. Our study provided new insights into the phylogeny of the Sinodielsia clade and valuable information on cp. genome evolution in Apioideae.

Abstract Background X/Y translocations are highly heterogeneity in terms of clinical genetic effects, and most patients lack complete pedigree analysis for clinical and genetic characterization. Results This study comprehensively analyzed the clinical and genetic characteristics of three new patients with X/Y translocations. Furthermore, cases with X/Y translocations reported in the literature and studies exploring the clinical genetic effects in patients with X/Y translocations were reviewed. All three female patients were carriers of X/Y translocations with different phenotypes. The karyotype for patient 1 was 46,X,der(X)t(X;Y)(p22.33;q12)mat, patient 2 was 46,X,der(X)t(X;Y)(q21.2;q11.2)dn, and patient 3 was 46,X,der(X)t(X;Y)(q28;q11.223)t(Y;Y)(q12;q11.223)mat. C-banding analysis of all three patients revealed a large heterochromatin region in the terminal region of the X chromosome. All patients underwent chromosomal microarray analysis, which revealed the precise copy number loss or gain. Data on 128 patients with X/Y translocations were retrieved from 81 studies; the phenotype of these patients was related to the breakpoint of the chromosome, size of the deleted region, and their sex. We reclassified the X/Y translocations into new types based on the breakpoints of the X and Y chromosomes. Conclusion X/Y translocations have substantial phenotypic diversity, and the genetic classification standards are not unified. With the development of molecular cytogenetics, it is necessary to combine multiple genetic methods to obtain an accurate and reasonable classification. Thus, clarifying their genetic causes and effects promptly will help in genetic counseling, prenatal diagnosis, preimplantation genetic testing, and improvement in clinical treatment strategies.

Abstract Background Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. Methods Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT‒PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. Results GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. Conclusions Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract

The phylogenetic status of Quercus subg. Cyclobalanopsis has long been controversial and the interspecific relationships of some species are unclear. At present, chloroplast genomes have been used to solve the phylogenetic problems of subg. Quercus and Castanea in the Fagaceae, but there are few researches on solving the phylogenetic problems of Quercus subg. Cyclobalanopsis with chloroplast genome information. To reveal the chloroplasts genome characteristics and phylogenetic relationships of Quercus ningangensis, Q. oxyodon, Q. gambleana and Q. neglecta. In this study, mature leaves of the above four species of Quercus subg. Cyclobalanopsis were selected for next-generation sequencing, and the chloroplast genome structure and characteristics were analyzed, phylogeny was studied in combination with related taxa. The results were as follows: (1) The chloroplast genome sequences of Q. ningangensis, Q. oxyodon, Q. gambleana and Q. neglecta were 160 906, 160 883, 160 832, 160 784 bp, respectively. They all encoded 133 genes, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. (2) The codons ending in A/T were preferred by the four species of Quercus subg. Cyclobalanopsis, and the variation regions of plastid genome mainly existed in non-coding sequences. (3) According to IR boundary analysis, ycf1 pseudogene was found in four species of Quercus subg. Cyclobalanopsis and expanded in IRb/SSC regions. (4) Phylogenetic analysis showed that Fagus and Trigonobalanus were differentiated early in Fagaceae, while subg. Quercus did not form a monophyly. The results of phylogenetic tree based on chloroplast genome were consistent with the nuclear marker plasmid markers. Interspersed between Ilex group and Cerris group in subg. Quercus. (5) The Flora of China and some local flora treated Q. gambleana as a separate species, while ZHOU Zhekun and DENG Min et al. treated Q. gambleana as a subspecies according to the characteristics of leaves. The phylogenetic status of Q. gambleana is still controversial. Based on the chloroplast genome information and previous morphological analysis results, the present study supported the idea that Q. gambleana existed as an independent species. This study provides basic data for discussing the phylogenetic status of the Quercus subg. Cyclobalanopsis, the division of its groups, and the resolution of doubtful relationships among them.

Abstract Background English as a Media of Instruction (EMI) teacher development project is based upon the framework for teacher Continuing Professional Development (CPD) and aims to effectively improve both the confidence and overall capacity of EMI lecturers. Kunming Medical University(KMU) conducted the EMI training project to improve teachers’ competence for MBBS education. This study aimed to assess teachers’ changes following the implementation of this training project, via the Kirkpatrick evaluation model. Methods A total of trainees (n = 84) were invited as the research objects. The effects of the EMI training project implemented in KMU were evaluated in terms of the reaction, learning, and behavior dimensions based on the Kirkpatrick model. The self-administered online anonymous questionnaires and observations of participants’ EMI lectures were administered to all participants to collect the data. Furthermore, to understand participants’ perceptions of the management and trainers of the training project, some open-ended questions were required to answer. Results Based on 1–3 level of the Kirkpatrick model, all participants were highly satisfied with the EMI training implementation on the reaction level, and expressed positive comments about the management of the training and trainers. On the learning level, participants’ scores on awareness of EMI teaching techniques increased significantly(t = 7.122, P

A new quinazolinone alkaloid named peniquinazolinone A (1), as well as eleven known compounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), and conidiogenone B (12), were isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all the compounds were elucidated by comprehensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher’s method. Compounds 2, 3, and 7 exhibited an optimal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed germination period of Rhodiola tibetica up to the 11th day.

Many studies have investigated how soil water availability in shallow soil affects forest transpiration, but how deep soil water status (below 1 m depth) alters tree water use remains poorly understood. To improve our understanding of how deep soil water changes tree transpiration dynamics, we measured soil water content (SWC) in more than 20 m depths, the radial sap flow profile and the leaf area index (LAI) in the 2017 growing season in 9-, 12-, 16-, 19- and 23-year-old afforested apple (Rosaceae) trees on the Chinese Loess Plateau. SWC was also measured in long-term cultivated farmland to derive SWC before afforestation. The results showed that there was no statistical difference in SWC in shallow soil among orchards (p > 0.05), while SWC in deep soil reduced rapidly with increasing tree age. The average SWC at 1–20 m decreased from 0.27 ± 0.02 cm3 cm−3 in farmland to 0.21 ± 0.03 cm3 cm−3 in the 23-year-old orchard. Moreover, water storage in deep soil decreased by 139 mm yr−1 between the 9- and 12-year-old stands, 105 mm yr−1 between the 12- and 16-year-old stands, 44 mm yr−1 between the 16- and 19-year-old stands, and 9 mm yr−1 from the 19- to 23-year-old stands, indicating that gradually decreased SWC in deep soil has restricted tree water use. Due to the changes in SWC, growing-season transpiration and the LAI peaked in the 16-year-old orchard and then decreased with increasing stand age. Growing-season transpiration in the 23-year-old orchard was only 77% of that in the 16-year stands, despite the older trees having larger diameters at the breast height. Our results suggest that soil water availability in deep soil plays an important role in regulating trees’ transpiration.

Purpose To discover the biological function and potential mechanism of LINC01936 in the development of lung squamous cell carcinoma (LUSC). Methods Transcriptome data of LUSC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the differentially expressed lncRNAs in LUSC and normal tissues by R “DEseq2”, “edgeR” and “limma” packages. The subcellular localization of LINC01936 was predicted by lncLocator. Cell proliferation and apoptosis were measured by CCK-8, MTT assay and Hoechst fluorescence staining. The migration and invasion were detected by Transwell assay. The function and pathway enrichment analysis were performed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set variation analysis (GSVA). The downstream targets of LINC01936 were predicted using RNA-Protein Interaction Prediction (RPISeq) program. The effect of LINC01936 on tumor immune infiltration was analyzed using Pearson Correlation Analysis using R “ggpubr” package. Results Based on the gene expression data of LUSC from TCGA database, 1,603, 1,702 and 529 upregulated and 536, 436 and 630 downregulated lncRNAs were obtained by DEseq2, edgeR and limma programs, respectively. For GSE88862 dataset, we acquired 341 differentially expressed lncRNAs (206 upregulated and 135 downregulated). Venn plot for the intersection of above differential expressed lncRNAs showed that there were 29 upregulated and 23 downregulated genes. LINC01936 was one of downregulated lncRNAs in LUSC tissues. The biological analysis showed that the overexpression of LINC01936 significantly reduced proliferation, migration and invasion of LUSC cells, and promoted cell apoptosis. The knockdown of LINC01936 promoted cell proliferation and metastasis. Pathway and GSVA analysis indicated that LINC01936 might participated in DNA repair, complement, cell adhesion and EMT, etc. LINC01936 was predicted to interact with TCF21, AOC3, RASL12, MEOX2 or HSPB7, which are involved in EMT and PI3K-AKT-MTOR pathway, etc. The expression of LINC01936 was also positively correlated with the infiltrating immune cells in LUSC. Conclusions LINC01936 is downregulated in LUSC. LINC01936 affected proliferation, migration and invasion of LUSC cells probably by EMT and immune infiltration, which might serve as a new target for the treatment of LUSC.

Summary: Single-stranded DNA-binding proteins (SSBs) have been regarded as indispensable replication factors. Herein, we report that the genes encoding the canonical SSB (SisSSB) and the non-canonical SSB (SisDBP) in Saccharolobus islandicus REY15A are not essential for cell viability. Interestingly, at a lower temperature (55°C), the protein level of SisSSB increases and the growth of ΔSisssb and ΔSisssbΔSisdbp is retarded. SisSSB exhibits melting activity on dsRNA and DNA/RNA hybrid in vitro and is able to melt RNA hairpin in Escherichia coli. Furthermore, the core SisSSB domain is able to complement the absence of cold-shock proteins in E. coli. Importantly, these activities are conserved in the canonical SSBs from Crenarchaeota species that lack bacterial Csp homologs. Overall, our study has clarified the function of the archaeal canonical SSBs which do not function as a DNA-processing factor, but play a role in the processes requiring melting of dsRNA or DNA/RNA hybrid.

Abstract Background The L1 cell adhesion molecule (L1CAM, OMIM 308840) gene is primarily expressed in the nervous system and encodes the L1 adhesion molecule protein. Variations in L1CAM cause a wide spectrum of X‐linked neurological disorders summarized as the L1 syndrome. Methods We report a 29‐year‐old pregnant woman who experienced multiple adverse pregnancy outcomes due to recurrent fetal hydrocephalus with an X‐linked recessive inheritance. Genomic DNA was extracted from the third aborted male fetus and analyzed via trio whole‐exome sequencing (WES). Total RNA was isolated from the pregnant woman to assess splicing variation at the mRNA level, and amniotic fluid was extracted from the woman for prenatal diagnosis on her fourth fetus. Results All four male fetuses were affected by severe hydrocephalus. We identified a maternally derived hemizygous splicing variation NM_000425.5:[c.3046 + 1G > A]; NP_000416.1 p.(Gly1016AspfsTer6) (chrX:153130275) in Intron 22 of the L1CAM. This variation disrupts the donor splice site and causes the retention of Intron 22, which results in frame shift and a premature termination codon at position 1021 with the ability to produce a truncated protein without the fifth fibronectin‐repeat III, transmembrane, and cytoplasmic domains or to induce the degradation of mRNAs by nonsense‐mediated mRNA decay. The same hemizygous variant was also detected in the amniocytes. Conclusion This report enhances our knowledge of genetic and phenotypic characteristics of X‐linked fetal hydrocephalus, providing a new genetic basis for prenatal diagnosis and pre‐implantation prenatal diagnosis.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited cerebral white matter disorder in children. Pathogenic variations in the causative gene MLC1 are found in approximately 76% of patients and are inherited in an autosomal recessive manner. In this study, we identified an IVS2 + 1delG variant in MLC1 in the firstborn girl of a pregnant woman who has the clinical features of MLC, including macrocephaly, motor development delay, progressive functional deterioration, and myelinopathy, whereas no obvious subcortical cysts were observed by magnetic resonance imaging of the brain. The proband is homozygous for the IVS2 + 1delG mutation, which was inherited from the parents. This variant disrupts the donor splice site, causing an abnormal transcript that results in a premature termination codon and produces a truncated protein, which was confirmed to affect splicing by MLC1 cDNA analysis. This variant was also detected in family members, and a prenatal diagnosis for the fetus was undertaken. Eventually, the couple gave birth to an unaffected baby. Furthermore, we conducted a long-term follow-up of the proband’s clinical course. This report improves our understanding of the genetic and phenotypic characteristics of MLC and provides a new genetic basis for prenatal diagnosis and genetic counseling.

Abstract Kinase, putative Endopeptidase, and Other Proteins of Small size (KEOPS) is a multisubunit protein complex conserved in eukaryotes and archaea. It is composed of Pcc1, Kae1, Bud32, Cgi121, and Gon7 in eukaryotes and is primarily involved in N6‐threonylcarbamoyl adenosine (t6A) modification of transfer RNAs (tRNAs). Recently, it was reported that KEOPS participates in homologous recombination (HR) repair in yeast. To characterize the KEOPS in archaea (aKEOPS), we conducted genetic and biochemical analyses of its encoding genes in the hyperthermophilic archaeon Saccharolobus islandicus. We show that aKEOPS also possesses five subunits, Pcc1, Kae1, Bud32, Cgi121, and Pcc1‐like (or Gon7‐like), just like eukaryotic KEOPS. Pcc1‐like has physical interactions with Kae1 and Pcc1 and can mediate the monomerization of the dimeric subcomplex (Kae1‐Pcc1‐Pcc1‐Kae1), suggesting that Pcc1‐like is a functional homolog of the eukaryotic Gon7 subunit. Strikingly, none of the genes encoding aKEOPS subunits, including Pcc1 and Pcc1‐like, can be deleted in the wild type and in a t6A modification complementary strain named TsaKI, implying that the aKEOPS complex is essential for an additional cellular process in this archaeon. Knock‐down of the Cgi121 subunit leads to severe growth retardance in the wild type that is partially rescued in TsaKI. These results suggest that aKEOPS plays an essential role independent of the cellular t6A modification level. In addition, archaeal Cgi121 possesses dsDNA‐binding activity that relies on its tRNA 3ʹ CCA tail binding module. Our study clarifies the subunit organization of archaeal KEOPS and suggests an origin of eukaryotic Gon7. The study also reveals a possible link between the function in t6A modification and the additional function, presumably HR.

Abstract Background Hair follicle stem cells (HFSCs) are considered as a promising cell type in the stem cell transplantation treatment of neurological diseases because of their rich sources, easy access, and the same ectoderm source as the nervous system. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that shows neuroprotective function in ischemic stroke. Here we assessed the therapeutic effects of HFSCs on ischemic stroke injury and the synthetic effect of HGF along with HFSCs. Methods Rat HFSCs were intravenously transplanted into a middle cerebral artery ischemia/reperfusion (I/R) rat model. Neurological scoring and TTC staining were performed to assess the benefits of HFSC transplantation. Inflammatory cytokines, blood–brain barrier integrity and angiogenesis within penumbra were estimated by Western blot and immunohistochemistry. The differentiation of HFSCs was detected by immunofluorescence method 2 weeks after transplantation. Results HFSC transplantation could significantly inhibit the activation of microglia, improve the integrity of blood–brain barrier and reduce brain edema. Moreover, the number of surviving neurons and microvessels density in the penumbra were upregulated by HFSC transplantation, leading to better neurological score. The combination of HFSCs and HGF could significantly improve the therapeutic benefit. Conclusion Our results indicate for the first time that HGF modified HFSCs can reduce I/R injury and promote the neurological recovery by inhibiting inflammatory response, protecting blood–brain barrier and promoting angiogenesis.

Abstract Background The cytoplasmic male sterility (CMS) of rice is caused by chimeric mitochondrial DNA (mtDNA) that is maternally inherited in the majority of multicellular organisms. Wild rice (Oryza rufipogon Griff.) has been regarded as the ancestral progenitor of Asian cultivated rice (Oryza sativa L.). To investigate the distribution of original CMS source, and explore the origin of gametophytic CMS gene, a total of 427 individuals with seventeen representative populations of O. rufipogon were collected in from Dongxiang of Jiangxi Province to Sanya of Hainan Province, China, for the PCR amplification of atp6, orfH79 and B-atp6-orfH79, respectively. Results The B-atp6-orfH79 and its variants (B-atp6-GSV) were detected in five among seventeen populations (i.e. HK, GZ, PS, TL and YJ) through PCR amplification, which could be divided into three haplotypes, i.e., BH1, BH2, and BH3. The BH2 haplotype was identical to B-atp6-orfH79, while the BH1 and BH3 were the novel haplotypes of B-atp6-GSV. Combined with the high-homology sequences in GenBank, a total of eighteen haplotypes have been revealed, only with ten haplotypes in orfH79 and its variants (GSV) that belong to three species (i.e. O. rufipogon, Oryza nivara and Oryza sativa). Enough haplotypes clearly demonstrated the uniform structural characteristics of the B-atp6-orfH79 as follows: except for the conserved sequence (671 bp) composed of B-atp6 (619 bp) and the downstream followed the B-atp6 (52 bp, DS), and GSV sequence, a rich variable sequence (VS, 176 bp) lies between the DS and GSV with five insertion or deletion and more than 30 single nucleotide polymorphism. Maximum likelihood analysis showed that eighteen haplotypes formed three clades with high support rate. The hierarchical analysis of molecular variance (AMOVA) indicated the occurrence of variation among all populations (F ST = 1; P

Abstract Background Muscle wasting is a common complication of chronic kidney disease (CKD) that is associated with higher mortality. Although the mechanisms of myofibre loss in CKD has been widely studied, the contribution of muscle precursor cell (MPC) senescence remains poorly understood. Senescent MPCs no longer proliferate and can produce proinflammatory factors or cytokines. In this study, we tested the hypothesis that the senescence associated secretory phenotype (SASP) of MPCs contributes to CKD‐induced muscle atrophy and weakness. Methods CKD was induced in mice by 5/6th nephrectomy. Kidney function, muscle size, and function were measured, and markers of atrophy, inflammation, and senescence were evaluated using immunohistochemistry, immunoblots, or qPCR. To study the impact of senescence, a senolytics cocktail of dasatinib + quercetin (D&Q) was given orally to mice for 8 weeks. To investigate CKD‐induced senescence at the cellular level, primary MPCs were incubated with serum from CKD or control subjects. The roles of specific proteins in MPC senescence were studied using adenoviral transduction, siRNA, and plasmid transfection. Results In the hindlimb muscles of CKD mice, (i) the senescence biomarker SA‐β‐gal was sharply increased (~30‐fold); (ii) the DNA damage response marker γ‐H2AX was increased 1.9‐fold; and (iii) the senescence pathway markers p21 and p16INK4a were increased 1.99‐fold and 2.82‐fold, respectively (all values, P

According to the China Earthquake Networks Center, a strong earthquake of M6.8 occurred in Luding County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China (102.08°E, 29.59°N), on September 5, 2022, with a focal depth of 16 km. Rapid determination of the source parameters of the earthquake sequence is vital for post-earthquake rescue, disaster assessment, and scientific research. Near-field seismic observations play a key role in the fast and reliable determination of earthquake source parameters. The numerous broadband seismic stations and strong-motion stations recently deployed by the National Earthquake Intensity Rapid Report and Early Warning project have provided valuable real-time near-field observation data. Using these near-field observations and conventional mid- and far-field seismic waveform records, we obtained the focal mechanism solutions of the mainshock and M ≥ 3.0 aftershocks through the waveform fitting method. We were further able to rapidly invert the rupture process of the mainshock. Based on the evaluation of the focal mechanism solution of the mainshock and the regional tectonic setting, we speculate that the Xianshuihe fault formed the seismogenic structure of the M6.8 strong earthquake. The aftershocks formed three spatially separated clusters with distinctly different focal mechanisms, reflecting the segmented nature of the Xianshuihe fault. As more high-frequency information has been applied in this study, the absolute location of the fault rupture is better constrained by the near-field strong-motion data. The rupture process of the mainshock correlates well with the spatial distribution of aftershocks, i.e., aftershock activities were relatively weak in the maximum slip area, and strong aftershock activities were distributed in the peripheral regions.

BackgroundSome studies have shown that PM2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM2.5-induced depression- and anxiety-like behaviors in mice. ObjectiveTo observe the effects of PM2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM2.5. MethodsEight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. ResultsThe percentage of open-arm entry [M(P25, P75)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P

Abstract It aims to examine the correlation between the expression of YTHDF1 and YTHDF2 and the clinical, pathological, and prognostic factors in HCC. The study was done using statistics from TCGA to establish the noted relationship. The degree of YTHDF1 and YTHDF2 protein expression in 88 HCC as well as the adjacent tissues was then determined through IHC examination, and we examined how that expression linked with other clinicopathological traits and clinical outcomes. Bioinformatics examination revealed that YTHDF1 and YTHDF2 expression was increased in HCC tissues, and poor pathology grade and prognosis were linked to high expression. YTHDF1 protein expression in IHC was notably higher in HCC tissue (p = .023). It was associated with age (p = .002) but not with other clinicopathological characteristics or prognoses. When compared to paraneoplastic tissues, the expression of the protein YTHDF2 was considerably higher in HCC tissues (p

In this study, phenolics extracted from male walnut flowers were purified and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. After ultrasonic extraction of male walnut flowers with 60% ethanol, AB-8, D3520, NKA-9, D101, and NKA macroporous adsorption resins were compared for purification. The AB-8 macroporous resin gave the best adsorption and desorption performance for 0.7 mg gallic acid equivalents/mL samples (pH 3.0) loaded at a flow rate of 1 mL/min. Elution was carried out with 50% ethanol without pH adjustment. The purity of the phenolics in the eluate (72.5%) was 3.1 times that in the original extract. Analysis by ultra-high-performance liquid chromatography tandem mass spectrometry identified 16 compounds, including phenolic acids, flavonoids, and coumarins in the purified phenolics. The most abundant compounds were chlorogenic acid, kaempferol, and methoxycoumarin. Two compounds were got in male walnut flowers for the first time, and those need yet to be proved by further experiments.

AbstractThe MADS-box transcription factor family plays an important role in regulating growth and signal transduction in animals and plants. TaMADS32 encodes a type II MADS-box transcription factor which is mainly expressed in wheat root system. In this study, we used bioinformatics methods to analyse TaMADS32, and investigate its function in plant root development and response to various abiotic stresses. We mapped TaMADS32 on chromosome 2B of wheat. Both TaMADS32 and its orthologs contained 7 exons and 6 introns and all the orthologous proteins have the MADS domains. Prokaryotic experiments showed that TaMADS32 could be expressed in prokaryotic cells. The predicted subcellular localization of TaMADS32 in plant cells was in the nucleus and in the cell membrane. Abiotic stresses (drought, heat and cold) can alter the expression of TaMADS32 in transgenic Arabidopsis. Phenotypic analysis showed that overexpression of TaMADS32 enhanced the tolerance of Arabidopsis to abiotic stresses. These results indicate that TaMADS32 is probably involved in the adaptation of plants to abiotic stress environments.

In this paper, the regional full waveform inversion of the broadband waveforms from China Seismic Network were conducted, and the focal mechanism solutions of the 18 earthquakes with M≥4.0 in the mainland of China from July 1 to September 30, 2022 were obtained. The centroid location and time shift of the M6.8 Luding, Sichuan earthquake were determinated by a grid search in the horizontal plane. The types of these focal mechanism solutions show 6 reverse faulting, 7 strike-slip faulting, 4 normal faulting and 1 unknown earthquakes.

Abstract The tripartite-motif (TRIM) family represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases. TRIM family is involved in a variety of cellular signaling transductions and biological processes. TRIM family also contributes to cancer initiation, progress, and therapy resistance, exhibiting oncogenic and tumor-suppressive functions in different human cancer types. Moreover, TRIM family members have great potential to serve as biomarkers for cancer diagnosis and prognosis. In this review, we focus on the specific mechanisms of the participation of TRIM family members in tumorigenesis, and cancer development including interacting with dysregulated signaling pathways such as JAK/STAT, PI3K/AKT, TGF-β, NF-κB, Wnt/β-catenin, and p53 hub. In addition, many studies have demonstrated that the TRIM family are related to tumor resistance; modulate the epithelial–mesenchymal transition (EMT) process, and guarantee the acquisition of cancer stem cells (CSCs) phenotype. In the end, we havediscussed the potential of TRIM family members for cancer therapeutic targets.

Pontocerebellar hypoplasia type 8(PCH8) is a rare neurodegenerative disorder, reportedly caused by pathogenic variants of the CHMP1A in autosomal recessive inheritance, and CHMP1A variants have also been implicated in other diseases, and yet none of the prenatal fetal features were reported in PCH8. In this study, we investigated the phenotype and genotype in a human subject with global developmental delay, including clinical data from the prenatal stage through early childhood. Prenatally, the mother had polyhydramnios, and the bilateral ventricles of the fetus were slightly widened. Postnatally, the infant was observed to have severely delayed psychomotor development and was incapable of visual tracking before 2 years old and could not fix on small objects. The young child had hypotonia, increased knee tendon reflex, as well as skeletal malformations, and dental crowding; she also had severe and recurrent pulmonary infections. Magnetic resonance imaging of the brain revealed a severe reduction of the cerebellum (vermis and hemispheres) and a thin corpus callosum. Through whole exome sequencing and whole genomics sequencing, we identified two novel compound heterozygous variations in CHMP1A [c.53 T > C(p.Leu18Pro)(NM_002768.5) and exon 1 deletion region (NC_000016.10:g.89656392_89674382del)]. cDNA analysis showed that the exon1 deletion region led to the impaired expression, and functional verification with zebrafish embryos using base edition indicated variant c.53 T > C (p.Leu18Pro), causing dysplasia of the cerebellum and pons. These results provide further evidence that CHMP1A variants in a recessive inheritance pattern contribute to the clinical characteristics of PCH8 and further expand our knowledge of the phenotype and genotype spectrum of PCH8.

The existing data regarding the effects of polyethylene (PE) microplastics (MPs) smaller than 5 mm in size on earthworms are insufficient to fully comprehend their toxicity. In this study, earthworms Eisenia fetida were exposed to artificially added PE at a concentration ranging from 0.05 to 20 g/kg soil (0.005%−2%) for 60 days to determine the concentration range causing negative effects on earthworms and to uncover the potential toxic mechanisms. The individual growth, reproduction, and metabolic enzyme activities, including phase I enzymes (cytochrome P450 [CYP] 1A2, 2B6, 2C9, and 3A4), and phase II metabolic enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione sulfotransferase (GST)), and metabolomics were measured. The observed variations in responses of multiple cross-scale endpoints indicated that individual indices are less responsive to PE MPs than metabolic enzymes or metabolomics. Despite the absence of significant alterations in growth inhibition based on body weight, PE MPs at concentrations equal to or exceeding 2.5 g/kg were found to exert a toxic effect on earthworms, which was evidenced by significant changes in metabolic enzyme activities (CYP1A2, 2B6, 2C9, and 3A4, SOD, CAT, and GST) and important small molecule metabolites screened based on metabolomics, likely due to the bioaccumulation of PE. The toxicity of PE MPs to earthworms is inferred to be associated with neurotoxicity, oxidative damage, decreased detoxification capacity, energy metabolism imbalance, and impaired amino acid and purine metabolism due to bioaccumulation. The findings of this study will enhance our understanding of the molecular toxicity mechanisms of PE MPs and contribute to a more accurate assessment of the ecological risks posed by PE MPs in soil.

Summary: Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of Bacteroides thetaiotaomicron through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.

ABSTRACT Forkhead-associated (FHA) domain proteins specifically recognize phosphorylated threonine via the FHA domain and are involved in signal transduction in various processes especially DNA damage response (DDR) and cell cycle regulation in eukaryotes. Although FHA domain proteins are found in prokaryotes, archaea, and bacteria, their functions are far less clear as compared to the eukaryotic counterparts, and it has not been studied whether archaeal FHA proteins play a role in DDR. Here, we have characterized an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) by genetic, biochemical, and transcriptomic approaches. We find that ΔSisarnA exhibits higher resistance to DNA damage agent 4-nitroquinoline 1-oxide (NQO). The transcription of ups genes, encoding the proteins for pili-mediated cell aggregation and cell survival after DDR, is elevated in ΔSisarnA. The interactions of SisArnA with two predicted partners, SisvWA1 (SisArnB) and SisvWA2 (designated as SisArnE), were enhanced by phosphorylation in vitro. ΔSisarnB displays higher resistance to NQO than the wild type. In addition, the interaction between SisArnA and SisArnB, which is reduced in the NQO-treated cells, is indispensable for DNA binding in vitro. These indicate that SisArnA and SisArnB work together to inhibit the expression of ups genes in vivo. Interestingly, ΔSisarnE is more sensitive to NQO than the wild type, and the interaction between SisArnA and SisArnE is strengthened after NQO treatment, suggesting a positive role of SisArnE in DDR. Finally, transcriptomic analysis reveals that SisArnA represses a number of genes, implying that archaea apply the FHA/phospho-peptide recognition module for extensive transcriptional regulation. IMPORTANCE Cellular adaption to diverse environmental stresses requires a signal sensor and transducer for cell survival. Protein phosphorylation and its recognition by forkhead-associated (FHA) domain proteins are widely used for signal transduction in eukaryotes. Although FHA proteins exist in archaea and bacteria, investigation of their functions, especially those in DNA damage response (DDR), is limited. Therefore, the evolution and functional conservation of FHA proteins in the three domains of life is still a mystery. Here, we find that an FHA protein from the hyperthermophilic Crenarchaeon Saccharolobus islandicus (SisArnA) represses the transcription of pili genes together with its phosphorylated partner SisArnB. SisArnA derepression facilitates DNA exchange and repair in the presence of DNA damage. The fact that more genes including a dozen of those involved in DDR are found to be regulated by SisArnA implies that the FHA/phosphorylation module may serve as an important signal transduction pathway for transcriptional regulation in archaeal DDR.

With global climate warming, recurring extreme heat and high temperatures irreversibly damage plants. Raspberries, known for their nutritional and medicinal value, are in high demand worldwide. Thus, it is important to study how high-temperature stress (HTS) affects raspberries. The physiological and biochemical responses and molecular genetic mechanisms of raspberry leaves to different HTS treatments were investigated: mild high temperature at 35°C (HT35), severe high temperature at 40°C (HT40), and the control at room temperature of 25°C (CK). The physiological results suggested that leaves in both the 35°C and 40°C treatments showed maximum relative conductivity at 4 d of stress, increasing by 28.54% and 43.36%, respectively, compared to CK. Throughout the stress period (0–4 d), malondialdehyde (MDA) and soluble protein contents of raspberry leaves increased under HT35 and HT40 treatments, while soluble sugar content first decreased and then increased. Catalase (CAT) activity increased, superoxide dismutase (SOD) activity first increased and then decreased, and peroxidase (POD) activity gradually decreased. Photosynthetic and fluorescence responses of raspberry leaves showed the most severe impairment after 4 d of stress. Transcriptomics results revealed significant alterations in 42 HSP family genes, two SOD-related differentially expressed genes (DEGs), 25 POD-related DEGs, three CAT-related DEGs, and 38 photosynthesis-related DEGs under HTS. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly enriched in photosynthesis-antenna proteins, pentose and glucuronide interconversion, phenylpropane biosynthesis, and indole alkaloid biosynthesis. HTS induced excessive ROS accumulation in raspberry leaves, causing oxidative damage in plant cells and subsequently reducing photosynthesis in raspberry leaves. This reduction in photosynthesis, in turn, affects photosynthetic carbon fixation and starch and sucrose metabolism, which, combined with phenol propane biosynthesis, mitigates the HTS-induced damage.

Summary: Vaccination is an effective means of preventing pneumococcal disease and SPY1 is a live attenuated pneumococcal vaccine we obtained earlier. We found IL-27 and its specific receptor (WSX-1) were increased in SPY1 vaccinated mice. Bacterial clearance and survival rates were decreased in SPY1 vaccinated IL-27Rα−/− mice. The vaccine-induced Th17 cell response and IgA secretion were also suppressed in IL-27Rα−/− mice. STAT3 and NF-κB signaling and expression of the Th17 cell polarization-related cytokines were also decreased in IL-27Rα−/− bone-marrow-derived dendritic cells(BMDC) stimulated with inactivated SPY1. The numbers of memory CD4+T cells were also decreased in SPY1 vaccinated IL-27Rα−/− mice. These results suggested that IL-27 plays a protective role in SPY1 vaccine by promoting Th17 polarization through STAT3 and NF-κB signaling pathways and memory CD4+T cells production in the SPY1 vaccine. In addition, we found that the immune protection of SPY1 vaccine was independent of aerobic glycolysis.

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.