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Abstract Background Commensal bacteria in the intestine release enzymes to degrade and ferment dietary components, producing beneficial metabolites. However, the regulatory effects of microbial-derived enzymes on the intestinal microbiota composition and the influence on host health remain elusive. Xylanase can degrade xylan into oligosaccharides, showing wide application in feed industry. Results To validate the immune-protective effects of xylanase, Nile tilapia was used as the model and fed with xylanase. The results showed that dietary xylanase improved the survival rate of Nile tilapia when they were challenged with Aeromonas hydrophila. The transcriptome analysis showed significant enrichment of genes related to interleukin-17d (il-17d) signaling pathway in the xylanase treatment group. High-throughput sequencing revealed that dietary xylanase altered the composition of the intestinal microbiota and directly promoted the proliferation of Allobaculum stercoricanis which could produce butyrate in vitro. Consequently, dietary xylanase supplementation increased the butyrate level in fish gut. Further experiment verified that butyrate supplementation enhanced the expression of il-17d and regenerating islet-derived 3 gamma (reg3g) in the gut. The knockdown experiment of il-17d confirmed that il-17d is necessary for butyrate to protect Nile tilapia from pathogen resistance. Flow cytometry analysis indicated that butyrate increased the abundance of IL-17D+ intestinal epithelial cells in fish. Mechanistically, butyrate functions as an HDAC3 inhibitor, enhancing il-17d expression and playing a crucial role in pathogen resistance. Conclusion Dietary xylanase significantly altered the composition of intestinal microbiota and increased the content of butyrate in the intestine. Butyrate activated the transcription of il-17d in intestinal epithelial cells by inhibiting histone deacetylase 3, thereby protecting the Nile tilapia from pathogen infection. This study elucidated how microbial-derived xylanase regulates host immune function, providing a theoretical basis for the development and application of functional enzymes. Video Abstract

Abstract Background Intravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health. Case presentation This case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient’s hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient’s cardiac structure and function. Conclusion This manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Abstract Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate’s function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. Graphical Abstract

Abstract Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia.

Abstract Background There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. Methods Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. Results The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p

Adding edible fungal polysaccharides to animal diets improves growth performance, meat quality, intestinal health, and immunity without adverse effects. This study aimed to evaluate the impact of Pleurotus citrinopileatus polysaccharide (PCP, including PCP250, PCP500, PCP750, and PCP1000 mg/kg) on the growth performance, meat quality, and microbial composition of Arbor Acre (AA) broilers (total 180) by metabolomics and high-throughput sequencing. The results showed that adding PCP enhanced chicken meat tenderness, redness (a*), and water retention and raised essential amino acids and flavor amino acids (such as umami and sweet amino acids) content. The metabolomics revealed that IMP, creatine, betaine, sarcosine, and taurine were related to improving meat quality in broilers by PCP addition. In addition, amino acid, purine, and lipid metabolism were the main metabolic pathways. Moreover, PCP could regulate muscle metabolism by increasing the relative abundance of Lachnospiraceae and Lactobacillus and the content of short-chain fatty acids (SCFAs). Therefore, PCP may become a promising new dietary supplement in the future, which may improve the yield and quality of broiler chickens.

Abstract Background To investigate the clinical efficacy of a percutaneous “tripod” combined with radiofrequency ablation and bone cement filling surgery in treating acetabular bone metastases. Methods We retrospectively analyzed 11 patients who underwent percutaneous “tripod” combined with radiofrequency ablation and bone cement filling for acetabular bone metastases at a tertiary care hospital from February 2021 to December 2022. Results 11 cases with 13 hips underwent this procedure, including two female patients who underwent both sides, and the rest were unilateral. All cases were followed up for 3–24 months, with a mean of 12 months and a median follow-up time of 11 months. Two of the 11 patients died by the final follow-up, and nine survived. One died 7 months after surgery, and one died 8 months after surgery; the survival of the deceased patients was 7.5 months (range: 7–8 months), with a median survival time of 7.5 months. All 11 patients completed the surgery successfully, and the average unilateral operation time was 167.4 min (148–193). The amelioration of postoperative pain, concomitant with improved quality of life, was observed significantly, ultimately resulting in a prolonged and sustained effect. Conclusions The combination of percutaneous “tripod”, radiofrequency ablation, and bone cement filling can effectively relieve pain without delaying the patient's systemic anti-tumor therapy and is a minimally invasive, safe, and effective procedure for the treatment of periacetabular metastases.

IntroductionThe gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis.MethodsAccording to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines.ResultsWe showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10.ConclusionDiverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB.

Abstract Background Soybean (Glycine max) meal is one of the important protein sources for fish, but the non-starch polysaccharides (NSP) in soybean meal impair the intestinal barrier function. Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism. Results Nile tilapia (Oreochromis niloticus) (4.09 ± 0.02 g) were fed with two diets including SM (soybean meal) and SMC (soybean meal + 3,000 U/kg xylanase) for 8 weeks. We characterized the effects of xylanase on the gut barrier, and the transcriptome analysis was performed to investigate the underlying mechanism. Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide (LPS) in serum. The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2 (MUC2) which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (perk)/activating transcription factor 4 (atf4) signaling pathways. Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut. Notably, dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia, and the data verified that sodium butyrate mirrored the beneficial effects of xylanase. Conclusions Collectively, supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia. The present study reveals the mechanism by which xylanase improves the intestinal barrier, and it also provides a theoretical basis for the application of xylanase in aquaculture.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defects in motile ciliary function and/or structure. Outer dynein arm docking complex subunit 1 (ODAD1) is an important component of the outer dynein arm docking complex (ODA-DC). To date, 13 likely pathogenic mutations of ODAD1 have been reported. However, the pathogenesis of ODAD1 mutations remains elusive. To investigate the pathogenesis of splice-site mutations in ODAD1 discovered in this study and those reported previously, molecular and functional analyses were performed. Whole-exome sequencing revealed a compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) in a patient with PCD, with c.598-2A>C being a novel mutation that resulted in two mutant transcripts. The compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) led to aberrant splicing that resulted in the absence of the wild-type ODAD1 and defects of the outer dynein arm in ciliary axonemes, causing a decrease in ciliary beat frequency. Furthermore, we demonstrated that the truncated proteins resulting from splice-site mutations in ODAD1 could retain partial function and inhibit the interaction between wild-type ODAD1 and ODAD3. The results of this study expand the mutational and clinical spectrum of PCD, provide more evidence for genetic counseling, and offer new insights into gene-based therapeutic strategies for PCD.

Solid tumor cells live in a highly dynamic mechanical microenvironment. How the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an enigma. Here, we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like cells. Mechanistically, integrin β8 was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein (YAP). YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), allowing MAFG to transactivate the stemness genes NANOG, SOX2, and NESTIN. Inactivation also restored β8 expression, thereby forming a closed mechanical loop. Importantly, MAFG expression is correlated with worse prognosis. Our findings provide mechanical insights into the regulation of tumor cell dedifferentiation, which has therapeutic implications for exploring innovative strategies to attack malignancies.

BackgroundPylephlebitis refers to an infective suppurative thrombosis that occurs in the portal vein and its branches. Concurrent pylephlebitis and subarachnoid hemorrhage (SAH) are rare but fatal for patients with sepsis. This scenario drives the clinicians into a dilemma of how to deal with coagulation and bleeding simultaneously.Case summaryAn 86-year-old man was admitted to hospital for chills and fever. After admission, he developed headache and abdominal distension. Neck stiffness, Kernig's and Brudzinski's sign were present. Laboratory tests discovered decreased platelet count, elevated inflammatory parameters, aggravated transaminitis, and acute kidney injury. Escherichia coli (E. coli) were identified in blood culture. Computed tomography (CT) revealed thrombosis in the superior mesenteric vein and portal veins. Lumbar puncture and Brain CT indicated SAH. The patient had eaten cooked oysters prior to illness. It was speculated that the debris from oyster shell might have injured his intestinal mucosa and resulted in bacterial embolus and secondary thrombosis in portal veins. The patient was treated with effective antibiotics, fluid resuscitation, and anticoagulation. The dose titration of low molecular weight heparin (LMWH) under close monitoring attributed to diminution of the thrombosis and absorption of SAH. He recovered and was discharged after 33-day treatment. One-year follow-up indicated that the post-discharge course was uneventful.ConclusionThis report describes a case of an octogenarian with E. coli septicemia who survived from concurrent pylephlebitis and SAH along with multiple organ dysfunction syndrome. For such patients with life-threatening complications, even in the acute stage of SAH, decisive employment of LMWH is essential to resolve thrombosis and confers a favorable prognosis.

While it is common for pregnant women to take anesthesia during surgery, the effects of prenatal anesthesia exposure (PAE) on the long-term neurodevelopment of the offspring remain to be clarified. Preclinical animal research has shown that in utero anesthetic exposure causes neurotoxicity in newborns, which is mainly characterized by histomorphological changes and altered learning and memory abilities. Regional birth cohort studies that are based on databases are currently the most convenient and popular types of clinical studies. Specialized questionnaires and scales are usually employed in these studies for the screening and diagnosis of neurodevelopmental disorders in the offspring. The time intervals between the intrauterine exposure and the onset of developmental outcomes often vary over several years and accommodate a large number of confounding factors, which have an even greater impact on the neurodevelopment of the offspring than prenatal anesthesia itself. This narrative review summarized the progress in prenatal anesthetic exposure and neurodevelopmental outcomes in the offspring from animal experimental research and clinical studies and provided a brief introduction to assess the neurodevelopment in children and potential confounding factors.

Objective Nerve growth factor (NGF) and tropomyosin kinase receptors A (TrKA) exert a crucial effect on the regulation of autonomic nervous system which contributes to the progress of atrial fibrillation (AF). Valvular heart disease (VHD) patients are more easily to induce the AF. We investigated whether NGF/TrKA could impact the occurrence of AF in VHD patients. Materials and methods Atrial tissues were resected from 30 VHD patients with chronic AF (n = 15, AF >6 months) or sinus rhythm (SR, n = 15). The expression of NGF, TrKA, protein kinase B (PKB/Akt), beta-isoforms of glycogen synthase kinase-3 (GSK3β), Serine473 phosphorylation of Akt (p-Ser473 Akt), Serine9 phosphorylation of GSK-3β (p-Ser9 GSK3β) in right atrial tissues and peripheral blood lymphocyte were quantified by Western blot. The localization of those genes expression was measured by immunohistochemistry. Double sandwich enzyme-linked immunosorbent assay was used to observe the trace changes of NGF-β in peripheral plasma. Results Our results revealed that the NGF expression was markedly elevated in the tissue of right atrial appendage and peripheral blood lymphocytes from AF patients compared with the SR patients. But, the expression of TrKA, GSK3β, p-Akt and p-GSK3β were decreased. There was no difference about the expression of Akt from the AF patients and the SR patients. The NGF-β level in peripheral blood plasma of patients with AF and SR was not statistical difference. Conclusion Thus, we thought that NGF/TrKA signaling pathway may be involved in the AF in the patients with VHD, inactivation of GSK3β could increase the incidence of AF, but not relevant to phosphorylation.

Language is central to the interactional nature of the social life within which it is situated. To react or respond in a particular situation, we must be able to recognize the social situation. Growing evidence has demonstrated the negative impact of perceived loneliness on late-life executive functions. Yet little is known about how social factors impact language processing for older people. The current study aims to fill this gap, first by assessing age-related changes in lexical processing during Chinese word reading, second, by examining whether older adults’ individual differences, such as processing speed and verbal abilities, modulate meaning retrieval and, third, by investigating whether perceived loneliness can hinder word reading. The use of compound words in Chinese enables significant sublexical ambiguity, requiring varying executive load during word recognition: when a word’s constituent characters carry multiple meanings, readers must consider the meaning contributions of both constituent characters and use top-down word information to determine the most accurate meaning of the ambiguous character, a process termed “sublexical ambiguity resolution.” In this study, adults read real Chinese words (including both sublexically ambiguous and unambiguous words) and pseudowords, and they were asked to make lexical decisions. Older adults exhibited greater lexicality effects (i.e., real words were easier to be identified than pseudowords) and similar sublexical ambiguity effects compared with young adults. Among older participants, processing speed could account for their ability to differentiate between words and pseudowords. In contrast, the level of perceived loneliness modulated the efficacy of sublexical ambiguity resolution: the participants with higher perceived loneliness displayed a greater sublexical ambiguity disadvantage effect. These results indicate that perceived loneliness may affect the use of contextual information in meaning retrieval during reading. The findings provide an important link between social connections and language processing.

Chinese milk vetch (CMV) is a leguminous green manure that is commonly cultivated in paddy fields and can partially substitute synthetic nitrogen fertilizer. However, the impacts of incorporating CMV on CH4 and N2O emissions are still a subject of controversy. Therefore, we conducted a field experiment over three years to investigate emissions under different substitution ratios: urea only (CF); incorporating a traditional amount of CMV (MV); and with incorporation ratios of 1/3 (MV1/3), 2/3 (MV2/3), and 4/3 (MV4/3) of MV for partial urea substitution. Compared with CF, MV2/3, MV, and MV 4/3 resulted in increased yields. MV and MV4/3 reduced N2O emissions but increased CH4 emissions by 28.61% and 85.60% (2019), 32.38% and 103.19% (2020), and 28.86% and 102.98% (2021), respectively, resulting in an overall increase in total global warming potential (except for MV in 2021). MV2/3 exhibited a low greenhouse gas intensity value ranging from 0.46 to 0.47. Partial least-squares-path model results showed that CH4 and N2O emissions were influenced by substitution ratios, which indirectly regulated the gene abundances of mcrA and nosZ. Overall, the impact of CMV on CH4 and N2O emissions was determined by substitution ratios. MV2/3, which involved partial substitution of synthetic N fertilizer with 15.0 t ha−1 of CMV, resulted in improved rice productivity without increasing CH4 and N2O emissions, making it a recommended approach in the study area.

Excessive chemical fertilizer application in greenhouse vegetable cultivation results in environmental risks and residual nutrients in the soil. Conventional plot experiments conducted in one field cannot recommend fertilizer reduction to farmers when the residual nutrient levels were various among different fields. In this study, nine plot experiments were simultaneously conducted in nine greenhouse fields where the soils could reflect different residual levels of nutrient, with two application rates (100 and 0%) for each nitrogen, phosphorus, and potassium fertilizer. The results showed that fertilizer reduction did not decrease vegetable yield when soil nitrate, Olsen–phosphorus, and exchangeable potassium were ≥173.3, 45.8, and 93.1 mg kg−1, respectively. However, no N treatment decreased vegetable yields in fields 1–3 because the inadequately residual nitrate (≤103.9 mg kg−1) in these fields led to low nitrate absorbed from sources other than chemical fertilizer, high recovery efficiencies of N, and high productivity of N absorbed from chemical fertilizer. Residual nitrate that soil EC could reflect was the limiting factor of yield under fertilizer reduction. This study indicated that reducing fertilizer in greenhouse vegetable cultivation should be based on the residual level of nutrients in the soil, which is meaningful in agricultural sustainability and environmental safety.

With the development of big data, data collection and publishing are symmetrical. The purpose of data collection is to better publish data. To better collect user data and promote data analysis, publishing massive amounts of data can better provide services for people’s lives. However, in the process of publishing data, the problem of low data availability caused by over protection is widespread. In addition, the attacker indirectly obtains the data of the target user by accessing the data of the user’s friends or neighbors, which leads to the disclosure of the user’s privacy. In order to solve these problems, a structure–attribute social network data publishing model is proposed. This model protects the privacy of user attribute data and prevents homogeneity attacks through attribute data perturbation. In addition, the model disrupts the structure of social networks by introducing uncertainty graphs into network partitions to generate published social network data. Our scheme has been tested on three public datasets, and the results show that our scheme can retain the social network structure as much as possible.

Semantic image segmentation is of crucial importance to many applications, such as autonomous driving, robot vision, and scene understanding. However, the border of a segmented image tends to be rough, and the labeling process is tedious and labor-intensive. Therefore, this study is the first proposing to use a deep generative adversarial network (GAN) with double-layered upsampling based on max-pooling indexed deconvolution. Our proposed upsampling method replaces the bilinear interpolation upsampling method; i.e., we fuse the deep deconvolution method by saving the indices of relative locations of the max weights computed during pooling. Combined with the deep GAN, our upsampling method can improve the extraction of low-resolution features, and compensate for the loss of the image size. To further reduce the whole network's dependence on labeled datasets, a weakly supervised feedback method is proposed. The unlabeled data can improve the generalization ability of the model. Considering the generalization to unseen image domains, we introduce transfer learning based on a deep GAN and a weakly supervised method. The segmentation model using the trained data in the source domain can obtain good segmentation in the target domain using transfer learning. Extensive experiments in various domains demonstrate the advantages of the proposed method compared to the generalization ability of semantic segmentation. This method also significantly decreases the dependence on labeled data and ensures the network accuracy.

In recent years, low-power wireless sensors with high flexibility, portability and computing capability have been extensively applied in areas such as military, medicine and mechanical equipment condition monitoring. In this paper, a novel symmetrical T-shaped trapezoidal micro piezoelectric energy harvester (STTM-PEH) is proposed to supply energy for wireless sensors monitoring the vibrations of mechanical equipment. Firstly, the finite element model (FEM) of the STTM-PEH is established. Secondly, the modal analysis of the T-shaped trapezoidal piezoelectric cantilever beam is carried out by finite element software and its vibration modes are obtained. Additionally, the structural characteristics of the STTM-PEH and the composition of piezoelectric patches are described. Furthermore, the effects of resistance, acceleration coefficient, substrate materials and structural parameters of the output performance of the STTM-PEH are researched. The results indicate that the output power of the STTM-PEH rises first and then falls with a change in resistance, while the output voltage does not increase as resistance increases to a certain extent. Meanwhile, selecting copper as the piezoelectric material of the T-shaped trapezoidal piezoelectric cantilever beam can generate a higher energy output. Finally, how the structural parameters, including piezoelectric patch thickness, substrate thickness and cantilever head length, affect the output performance of the STTM-PEH is studied, which illustrates that the load range of the STTM-PEH can be appropriately broadened by adjusting the length of the cantilever beam head. This research is valuable for designing a novel high performance piezoelectric energy harvester.

Entecavir (ETV) is a first‐line therapy for chronic hepatitis B virus (HBV), demonstrating potent suppression of HBV DNA and a high barrier to viral resistance. Previous studies revealed that ETV‐resistant (ETVr) HBV DNA resulted from substitutions in the HBV reverse transcriptase (RT) at positions rtT184, rtS202, or rtM250 in combination with lamivudine resistance (LVDr) substitutions rtM204I/V±rtL180M. In vitro, viral variants exhibit varying degrees of ETV susceptibility and replication capacity depending on specific resistance substitutions. To explore the potential for additional pathways to ETVr, HBV RT sequences from 982 evaluable patients enrolled in 17 ETV clinical studies were analyzed. Thirty novel emergent substitutions at amino acid positions not previously associated with HBV nucleos(t)ide drug resistance were observed in at least 2 patients and were identified in patient‐derived HBV with a wild‐type, LVDr, or ETVr RT sequence. Phenotypic analysis of these substitutions indicated that they had no effect on ETV susceptibility. Phenotypic analysis was also performed on patient‐derived HBV RT sequences from 10 LVD‐naive and 13 LVD‐experienced patients with virologic breakthrough and emergent novel substitutions while on ETV treatment. One LVD‐experienced patient‐derived HBV RT harboring LVDr substitutions rtL180M+rtM204V with rtA181C displayed reduced ETV susceptibility (122‐fold greater than wild‐type HBV) and remained susceptible to adefovir and tenofovir. HBV harboring the rtA181C substitution without LVDr substitutions rtL180M+rtM204V remained susceptible to inhibition by ETV, adefovir, and tenofovir, although cross‐resistance to LVD and telbivudine was observed. Conclusion: An integrated genotypic analysis of HBV RT sequences from patients with chronic HBV treated with ETV led to the discovery of the novel ETVr substitution rtA181C. This substitution was always detected in combination with LVDr substitutions rtL180M+rtM204V in ETV‐treated patients.

With the development of industry IoT, microprocessors and sensors are widely used for autonomously transferring information to cyber-physics systems. Massive quantities and huge power consumption of the devices result in a severe increment of the chemical batteries, which is highly associated with problems, including environmental pollution, waste of human/financial resources, difficulty in replacement, etc. Driven by this issue, mechanical energy harvesting technology has been widely studied in the last few years as a great potential solution for battery substitution. Therefore, the piezoelectric generator is characterized as an efficient transformer from ambient vibration into electricity. In this paper, a spoke-like piezoelectric energy harvester is designed and fabricated with detailed introductions on the structure, materials, and fabrication. Focusing on improving the output efficiency and broadening the pulse width, on the one hand, the energy harvesting circuit is optimized by adding voltage monitoring and regulator modules. On the other hand, magnetic mass is adopted to employ the magnetic field of repulsive and upper repulsion–lower attraction mode. The spoke-like piezoelectric energy harvester suggests broadening the frequency domain and increasing the output performance, which is prepared for wireless sensors and portable electronics in remote areas and harsh environments.

Connexin (Cx) family members form hemichannels (HCs) and gap junctions (GJs). Biological functions of Cx HCs have not been adequately characterized due to the inability to selectively target HCs or GJs. Recently, we developed a 6-mer peptide mimetic (P5) of the first extracellular loop of Cx43 and showed that it can block the permeability of HCs but not GJs formed by Cx43. In this study, we further characterized the HC blocking property of P5 and investigated the role of Cx HCs in acute lung injury (ALI). We found that P5 administration decreased HC permeability, in pulmonary microvascular endothelial cells, HepG2 cells, and even Cx43-deficient astrocytes, which express different sets of Cxs, suggesting that P5 is a broad spectrum Cx HC blocker. In addition, P5 reduced HC permeability of alveolar cells in vivo. Moreover, P5 decreased endotoxin-induced release, by vascular endothelial cells in vitro, of high mobility group box protein 1 (HMGB1), a critical mediator of acute lung injury (ALI), and reduced HMGB1 accumulation in bronchoalveolar lavage fluid (BALF) of mice subjected to intratracheal endotoxin instillation. Furthermore, P5 administration resulted in a significant decrease in the concentrations of ALT, AST, and LDH in the BALF, the accumulation of leukocytes in alveoli, and the mortality rate of mice subjected to ALI. Wright-Giemsa staining showed that P5 caused similar reductions of both neutrophils and monocytes in BALF of ALI mice. Together, these results suggest that Cx HCs mediate HMGB1 release, augment leukocyte recruitment, and contribute to ALI pathology.

With the rapid development of microelectronics technology, low-power electronic sensors have been widely applied in many fields, such as Internet of Things, aerospace, and so on. In this paper, a symmetrical ring-shaped piezoelectric energy harvester (SR-PEH) is designed to provide energy for the sensor to detect the ambient temperature. The finite element method is used by utilizing software COMSOL 5.4, and the electromechanical coupling model of the piezoelectric cantilever is established. The output performance equations are proposed; the microelectromechanical system (MEMS) integration process of the SR-PEH, circuit, and sensor is stated; and the changing trend of the output power density is explained from an energy perspective. In the logarithmic coordinate system, the results indicate that the output voltage and output power are approximately linear with the temperature when the resistance is constant. In addition, the growth rate of the output voltage and output power decreases with an increase of resistance under the condition of constant temperature. In addition, with an increase of temperature, the growth rate of the output power is faster than that of the output voltage. Furthermore, resistance has a more dramatic effect on the output voltage, whereas temperature has a more significant effect on the output power. More importantly, the comparison with the conventional cantilever-shaped piezoelectric energy harvester (CC-PEH) shows that the SR-PEH can improve the output performance and broaden the frequency band.

The p21-activated kinase 3 (PAK3) and the serum and glucocorticoid-induced kinase 2 (SGK2) have been previously proposed as essential kinases for human papillomavirus positive (HPV+) cervical cancer cell survival. This was established using a shRNA knockdown approach. To validate PAK3 and SGK2 as potential targets for HPV+ cervical cancer therapy, the relationship between shRNA-induced phenotypes in HPV+ cervical cancer cells and PAK3 or SGK2 knockdown was carefully examined. We observed that the phenotypes of HPV+ cervical cancer cells induced by various PAK3 and SGK2 shRNAs could not be rescued by complement expression of respective cDNA constructs. A knockdown-deficient PAK3 shRNA with a single mismatch was sufficient to inhibit HeLa cell growth to a similar extent as wild-type PAK3 shRNA. The HPV+ cervical cancer cells were also susceptible to several non-human target shRNAs. The discrepancy between PAK3 and SGK2 shRNA-induced apoptosis and gene expression knockdown, as well as cell death stimulation, suggested that these shRNAs killed HeLa cells through different pathways that may not be target-specific. These data demonstrated that HPV+ cervical cancer cell death was not associated with RNAi-induced PAK3 and SGK2 knockdown but likely through off-target effects.

Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER-negative human breast cancer.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1β, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells. [ABSTRACT FROM AUTHOR]

The magnetotelluric (MT) method is a widely used geophysical technique for deep structure exploration. However, rapid industrial development has resulted in significant anthropogenic interference for practical applications of this method in recent years. To carry out MT survey in regions with strong electromagnetic (EM) noise, we develop a strategy, in which part of MT sites are set for night time period and a newly proposed automatic clustering method based on MT signal patterns is applied to process measured data from Yingde area in Guangdong. The MT sites are employed in night time to avoid human activity and measure the quiet time MT signal to make sure that we can capture portion of MT signal. Based on cosine similarity, we can use clustering algorithms to separate the signals from the noise. The application of this strategy for geothermal exploration in Yingde area in Guangdong, indicates the validity of our proposed strategy for real geothermal detection. [ABSTRACT FROM AUTHOR]

Elevation of reactive oxygen species (ROS) levels is a general consequence of tumor cells' response to treatment and may cause tumor cell death. Mechanisms by which tumor cells clear fatal ROS, thereby rescuing redox balance and entering a chemoresistant state, remain unclear. Here, we show that cysteine sulfenylation by ROS confers on aryl hydrocarbon receptor (AHR) the ability to dissociate from the heat shock protein 90 complex but to bind to the PPP1R3 family member PPP1R3C of the glycogen complex in drug-treated tumor cells, thus activating glycogen phosphorylase to initiate glycogenolysis and the subsequent pentose phosphate pathway, leading to NADPH production for ROS clearance and chemoresistance formation. We found that basic ROS levels were higher in chemoresistant cells than in chemosensitive cells, guaranteeing the rapid induction of AHR sulfenylation for the clearance of excess ROS. These findings reveal that AHR can act as an ROS sensor to mediate chemoresistance, thus providing a potential strategy to reverse chemoresistance in patients with cancer. [ABSTRACT FROM AUTHOR]