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Adenosquamous carcinoma (ASC) of the duodenum is a malignant tumor that combines adenocarcinoma and squamous cell carcinoma components. Case reports of ASC are rare, and our understanding of the complex clinicopathological features and treatment strategies for the disease remains incomplete. The current study presents a case of duodenal ASC and discusses the available literature on this rare condition. A 55-year-old male patient presented with a history of jaundice and fever, with pruritus and clay-colored stools. Preoperative investigations suggested an increase in transaminase, bilirubin and tumor markers. Enhanced magnetic resonance imaging of the abdomen revealed a mass in the descending duodenum and another in the pancreatic region, without distant metastases. An endoscopy of the upper gastrointestinal tract revealed an infiltrative growth mass invading the duodenal papilla in the descending part of the duodenum. The patient underwent a Whipple procedure. Histopathological and immunohistochemical examinations confirmed duodenal ASC. Although an R0 resection was performed, the patient developed hepatic metastases 2 months after surgery and succumbed 6 months post-surgery. This case underscores the aggressive nature of duodenal ASC and the need for further studies to develop effective treatment interventions., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Zhang et al.)

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (P max ) (named MFC-HP) and lower P max (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased P max of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH 4 + -N removal and maintained high P max (424.33 mW/m 2 ) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bioelectrochemical systems (BESs) have shown great potential in enhancing sulfamethoxazole (SMX) removal. However, electroactive biofilms (EBs) constructed with single potentials struggle due to limited biocatalytic activity, hindering deep SMX degradation. Here, we constructed a double-working potential BES (BES-D) to investigate its ability to eliminate SMX and reduce the levels of corresponding antibiotic resistance genes (ARGs). The preferable electrochemical activity of EB in BES-D was confirmed by electrochemical characterization, EPS analysis, physical structure, viability of the biofilm, and cytochrome content. BES-D exhibited a notably greater SMX removal efficiency (94.2 %) than did the single-working potential BES (BES-S) and the open-circuit group (OC). Degradation pathway analysis revealed that the cooperative EB could accelerate the in-depth removal of SMX. Moreover, EB interaction in BES-D decreased the relative abundance of ARGs in biofilms compared to that in BES-S, although the absolute number of ARG copies increased in BES-D effluents. Compared to those in BES-S and OC, more complex cross-niche microbial associations in the EB of BES-D were observed by network analysis of the bacterial community and ARG hosts, enhancing the degradation efficiency of SMX. In conclusion, BES-D has significant potential for SMX removal and the enhancement of EB activity. Nonetheless, the risk of ARG dissemination in effluent remains a concern., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbial degradation plays a crucial role in removing sulfonamides from soil, enhancing sulfamethoxazole (SMX) remediation. To further augment SMX removal efficiency and mitigate the transmission risk associated with antibiotic resistance genes (ARGs), this study proposes a novel approach that integrates micro-animals, microorganisms, and microbial fuel cell (MFC) technology. The results showed that earthworm-MFC synergy substantially reduces SMX content and ARGs abundance in soil. The introduction of earthworms enhances humus content, facilitating electron transfer within MFC and consequently improving current generation. Furthermore, electrical stimulation applied to earthworms led to increased protein secretion and enhanced antioxidant system activity, thereby accelerating SMX degradation. Earthworms also foster MFC-associated bacterial growth and SMX-degrading bacteria proliferation, augmenting MFC treatment efficacy. This synergistic effect significantly augmented the overall efficacy of MFC treatment for antibiotics. Overall, integrating earthworm activity with MFC technology effectively optimizes electricity generation and enhances pollutant removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth., Methods: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role., Results: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes., Conclusions: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to establish a simple and practical grading system for evaluating the status of the sphincter of Oddi (SO) during intraoperative choledochoscopy. This system helps identify relevant variables that influence the status of the SO and provides recommendations for preventing stone recurrence., Methods: Ninety-three patients were selected retrospectively from a total of 316 patients diagnosed with choledocholithiasis between July 2020 and June 2023. All patients underwent common bile duct (CBD) exploration surgery and intraoperative choledochoscopy. The status of the SO was assessed during choledochoscopy. According to the severity of the condition, the patients were categorized into 4 groups. Data from each group, grades 1, 2, 3, 4, was analyzed statistically., Results: The number of patients in grade 1 was significantly lower than that of the other 3 groups. Except for grade 1, patients in grade 4 exhibited significant differences compared with the other 2 groups in terms of the diameter of the CBD, size of stones, presence of pneumobilia, and history of endoscopic retrograde cholangiopancreatography (ERCP) ( P <0.05). There were no significant differences between the groups in terms of sex, age, liver function, number of stones, history of gastrectomy, cholecystectomy, or CBD exploration., Conclusions: The grading system helps us classify different sphincter functions and better understand the formation of choledocholithiasis by subdividing the status of the SO. Endoscopic sphincterotomy (EST) treatment can easily result in the loss of SO function, which increases the risk of stone recurrence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Antibiotic resistance genes (ARGs) have been steadily increasing due to the extensive overuse of antibiotics in the marine environment. Currently, the research considering ARGs distribution in marine ecosystems gains more interest. As the coastal sea has been regarded as one of the most polluted areas by antibiotic contaminants in China. However, no comprehensive review of the spatial distribution of ARGs in marine environment surrounding China. The main objective of this review is to investigate the level, characteristic, and spatial distribution of ARGs in the marine environment (seawater and sediments) surrounding China. Key sea areas, such as Bohai Sea, Yellow Sea, East China Sea, and South China Sea were selected in this review. The marine environment was the reservoir of ARGs, and ARGs in seawater were generally 1 to 2 orders of magnitude higher than that in sediments. Total ARGs were more abundant in the Yellow Sea, followed by the Bohai Sea, the East China Sea, and the South China Sea. This study raises questions regarding the spread and distribution for antibiotic resistance in marine environments., Competing Interests: Declaration of competing interest The authors declare that they have no competing., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Unlike graphene derived from graphite, borophenes represent a distinct class of synthetic two-dimensional materials devoid of analogous bulk-layered allotropes, leading to covalent bonding within borophenes instead of van der Waals (vdW) stacking. Our investigation focuses on 665 vdW-stacking boron bilayers to uncover potential bulk-layered boron allotropes through vdW stacking. Systematic high-throughput screening and stability analysis reveal a prevailing inclination toward covalently bonded layers in the majority of boron bilayers. However, an intriguing outlier emerges in δ 5 borophene, demonstrating potential as a vdW-stacking candidate. We delve into electronic and topological structural similarities between δ 5 borophene and graphene, shedding light on the structural integrity and stability of vdW-stacked boron structures across bilayers, multilayers, and bulk-layered allotropes. The δ 5 borophene analogues exhibit metallic properties and characteristics of phonon-mediated superconductors, boasting a critical temperature near 22 K. This study paves the way for the concept of "borophite", a long-awaited boron analogue of graphite.

Biochar is a carbon-neutral tool for combating climate change. Artificial intelligence applications to estimate the biochar mitigation effect on greenhouse gases (GHGs) can assist scientists in making more informed solutions. However, there is also evidence indicating that biochar promotes, rather than reduces, N 2 O emissions. Thus, the effect of biochar on N 2 O remains uncertain in constructed wetlands (CWs), and there is not a characterization metric for this effect, which increases the difficulty and inaccuracy of biochar-driven alleviation effect projections. Here, we provide new insight by utilizing machine learning-based, tree-structured Parzen Estimator (TPE) optimization assisted by a meta-analysis to estimate the potency of biochar-driven N 2 O mitigation. We first synthesized datasets that contained 80 studies on global biochar-amended CWs. The mitigation effect size was then calculated and further introduced as a new metric. TPE optimization was then applied to automatically tune the hyperparameters of the built extreme gradient boosting (XGBoost) and random forest (RF), and the optimum TPE-XGBoost obtained adequately achieved a satisfactory prediction accuracy for N 2 O flux (R 2  = 91.90%, RPD = 3.57) and the effect size (R 2  = 92.61%, RPD = 3.59). Results indicated that a high influent chemical oxygen demand/total nitrogen (COD/TN) ratio and the COD removal efficiency interpreted by the Shapley value significantly enhanced the effect size contribution. COD/TN ratio made the most and the second greatest positive contributions among 22 input variables to N 2 O flux and to the effect size that were up to 18% and 14%, respectively. By combining with a structural equation model analysis, NH 4 + -N removal rate had significant negative direct effects on the N 2 O flux. This study implied that the application of granulated biochar derived from C-rich feedstocks would maximize the net climate benefit of N 2 O mitigation driven by biochar for future biochar-based CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Salidroside (Sal), the main bioactive substance in Rhodiola rosea , is a promising functional food component with a wide range of pharmacological effects, but its biological activity is challenging to sustain due to its short half-life, low oral bioavailability, and susceptibility to environmental factors. The aim of this study was to investigate the effect of sodium alginate (SA) concentration on the construction of W/O/W emulsion in the protection of Sal. With the escalation of SA concentrations, the range of droplet size distribution was smaller and the droplets were more uniform. When the concentration of SA was 2 %, the average droplet size reached 9.1 ± 0.1 μm, and the encapsulation efficiency of Sal was 77.8 ± 1.8 %. Moreover, the double emulsion with 2 % SA was the most stable for 28 days at 4 °C since the oil droplets were embedded in the network structure of SA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Common wheat ( Triticum aestivum L.) is a global staple food, while nitrogen (N) limitation severely hinders plant growth, seed yield, and grain quality of wheat. Genetic variations in the responses to low N stresses among allohexaploid wheat (AABBDD, 2 n = 6 x = 42) genotypes emphasize the complicated regulatory mechanisms underlying low N tolerance and N use efficiency (NUE). In this study, hydroponic culture, inductively coupled plasma mass spectrometry, noninvasive microtest, high-performance liquid chromatography, RNA-seq, and bioinformatics were used to determine the differential growth performance, ionome and phytohormone profiles, and genome-wide expression profiling of wheat plants grown under high N and low N conditions. Transcriptional profiling of NPFs, NRT2s, CLCs, SLACs/SLAHs, AAPs, UPSs, NIAs, and GSs characterized the core members, such as TaNPF6.3-6D , TaNRT2.3-3D , TaNIA1-6B , TaGLN1;2-4B , TaAAP14-5A / 5D , and TaUPS2-5A , involved in the efficient transport and assimilation of nitrate and organic N nutrients. The low-N-sensitivity wheat cultivar XM26 showed obvious leaf chlorosis and accumulated higher levels of ABA, JA, and SA than the low-N-tolerant ZM578 under N limitation. The TaMYB59 - 3D- TaNPF7.3 / NRT1.5-6D module-mediated shoot-to-root translocation and leaf remobilization of nitrate was proposed as an important pathway regulating the differential responses between ZM578 and XM26 to low N. This study provides some elite candidate genes for the selection and breeding of wheat germplasms with low N tolerance and high NUE.

Variations in the resistance to potassium (K) deficiency among rapeseed genotypes emphasize complicated regulatory mechanisms. In this study, a low-K-sensitivity accession (L49) responded to K deficiency with smaller biomasses, severe leaf chlorosis, weaker photosynthesis ability, and deformed stomata morphology compared to a low-K resistant accession (H280). H280 accumulated more K + than L49 under low K. Whole-genome resequencing (WGS) revealed a total of 5,538,622 single nucleotide polymorphisms (SNPs) and 859,184 insertions/deletions (InDels) between H280 and L49. RNA-seq identified more differentially expressed K + transporter genes with higher expression in H280 than in L49 under K deficiency. Based on the K + profiles, differential expression profiling, weighted gene coexpression network analysis, and WGS data between H280 and L49, BnaC4.AKT1 was proposed to be mainly responsible for root K absorption-mediated low K resistance. BnaC4.AKT1 was expressed preferentially in the roots and localized on the plasma membrane. An SNP and an InDel found in the promoter region of BnaC4.AKT1 were proposed to be responsible for its differential expression between rapeseed genotypes. This study identified a gene resource for improving low-K resistance. It also facilitates an integrated knowledge of the differential physiological and transcriptional responses to K deficiency in rapeseed genotypes.

Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation., Methods: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS)., Results: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs., Conclusion: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To explore whether the protein Deglycase protein 1 (DJ1) can ameliorate Alzheimer's disease (AD)-like pathology in Amyloid Precursor Protein/Presenilin 1 (APP/PS1) double transgenic mice and its possible mechanism to provide a theoretical basis for exploring the pathogenesis of AD., Methods: Adeno-associated viral vectors (AAV) of DJ1-overexpression or DJ1-knockdown were injected into the hippocampus of 7-month-old APP/PS1 mice to construct models of overexpression or knockdown. Mice were divided into the AD model control group (MC), AAV vector control group (NC), DJ1-overexpression group (DJ1 + ), and DJ1-knockdown group (DJ1 - ). After 21 days, the Morris water maze test, immunohistochemistry, immunofluorescence, and western blotting were used to evaluate the effects of DJ1 on mice., Results: DJ1 + overexpression decreased the latency and increased the number of platform traversals in the water maze test. DJ1 - cells were cured and atrophied, and the intercellular structure was relaxed; the number of age spots and the expression of AD-related proteins were significantly increased. DJ1 + increased the protein expression of Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), light chain 3 (LC3), phosphorylated AMPK (p-AMPK), and B cell lymphoma-2 (BCL-2), as well as the antioxidant levels of total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), and Glutathione peroxidase (GSH-PX), while decreasing the levels of Kelch-like hydrates-associated protein 1 (Keap1), mammalian target of rapamycin (mTOR), p62/sequestosome1 (p62/SQSTM1), Caspase3, and malondialdehyde (MDA)., Conclusion: DJ1-overexpression can ameliorate learning, memory, and AD-like pathology in APP/PS1 mice, which may be related to the activation of the NRF2/HO-1 and AMPK/mTOR pathways by DJ1., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The utilization of membrane foulant is expected to push forward the developments of membrane bioreactor (MBR). In this study, the combination of microbial fuel cell (MFC) with bio-electrochemical enhanced hydrolysis process was proposed, and three systems were conducted to utilize the membrane foulant and simultaneously harvest electricity. Polysaccharides (PS), proteins (PN) and humic acid (HA) concentration variations and the fluorescent compound changes in different chambers revealed the biodegradability of membrane foulant. Optimized HRT improved the hydrolysis of membrane foulant while allowing MFC to utilize the biodegradable components efficiently. MFC-MFC system had the highest voltage and satisfactory effluent quality at HRT of 1 d. Microbial community structure analysis indicated that Proteobacteria, Planctomycetes and Bacteroidetes were the majority phyla and network analysis further revealed that Proteobacteria played a key role in membrane foulant utilization. This study suggests that MFC hybrid systems has potential application for synchronous membrane foulant reuse and energy recovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A coupled system comprised of a biofilm electrode reactor (BER) and a manganese ore substrate microbial fuel cell-constructed wetland (MFC-CW) system was used to remove co-exposed antibiotic and Zn (II), as well as simultaneously reduce copies of antibiotic resistance genes (ARGs) in the current study. In this system, BER primarily reduced the concentrations of antibiotics and Zn (II), and the effluent was used as the input to the MFC-CW, thereby providing electricity to BER. Co-exposure to a high concentration of Zn (II) decreased the relative abundances (RAs) of ARGs in the BER effluent, whereas the remaining sub-lethal concentration of Zn (II) increased the RAs of ARGs in the MFC-CW effluent. Even though the absolute copies of ARGs in the effluents increased during co-exposure, the total number of target ARG copies in the effluent of MFC-CW was significantly lower than that of BER. Moreover, BER pre-treatment eliminated most of Zn (II), which improved the electrical power generation characteristic of the MFC-CW unit. Correspondingly, the bacterial community and the ARGs hosts were analyzed to demonstrate the mechanism. In conclusion, the coupled system demonstrates significant potential to reduce antibiotics, Zn (II) and environmental risks posed by ARGs., Competing Interests: Conflicts of interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergic A11-SDH ) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1 + ) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1 + neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1 + neurons form synapses with GRP receptor-expressing (GRPR + ) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1 + neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1 + neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch., (© 2023 The Authors.)

Osmotic membrane bioreactors (OMBRs) are considered a suitable technology for treating wastewater containing tetracycline due to their high rejection and biodegradation efficiency. However, the impact of membrane fouling layer (i.e., chemical composition, microbial composition, and formation) on the filtration and biodegradation of tetracycline is still unclear. Herein, the effects of draw solute concentration and type on the formation of a membrane fouling layer for tetracycline filtration and its relationship with microbial activity were investigated. The results showed that over 99% of tetracycline was retained on the feed side by membrane rejection, and the fouling layer played an important role in tetracycline filtration. Specifically, membrane foulants resulted in a more hydrophilic membrane facilitating tetracycline filtration, while the tetracycline-degrading genera from the fouled membrane promoted tetracycline degradation. The structure equation model showed that tetracycline filtration dominated by electrostatic repulsion between tetracycline and the fouled membrane was more important than tetracycline degradation for tetracycline removal (path coefficient of 0.655 vs. 0.395). This study provided insights into the combined effect of membrane foulants and microorganisms on tetracycline removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Manganese ore substrate up-flow microbial fuel cell constructed wetland (UCW-MFC(Mn)) as an innovative wastewater treatment technology for purifying antibiotics and electricity generation with few antibiotic resistance genes (ARGs) generation has attracted attention. However, antibiotic purifying effects should be further enhanced. In this study, a biofilm electrode reactor (BER) that needs direct current driving was powered by a Mn ore anode (UCW-MFC(Mn)) to form a coupled system without requiring direct-current source. Removal efficiencies of sulfadiazine (SDZ), ciprofloxacin (CIP) and the corresponding ARGs in the coupled system were compared with composite (BER was powered by direct-current source) and anaerobic systems (both of BER and UCW-MFC were in open circuit mode). The result showed that higher antibiotic removal efficiency (94% for SDZ and 99.1% for CIP) in the coupled system was achieved than the anaerobic system (88.5% for SDZ and 98.2% for CIP). Moreover, electrical stimulation reduced antibiotic selective pressure and horizontal gene transfer potential in BER, and UCW-MFC further reduced ARG abundances by strengthening the electro-adsorption of ARG hosts determined by Network analysis. Bacterial community diversity continuously decreased in BER while it increased in UCW-MFC, indicating that BER mitigated the toxicity of antibiotic. Degree of modularity, some functional bacteria (antibiotic degrading bacteria, fermentative bacteria and EAB), and P450 enzyme related to antibiotic and xenobiotics biodegradation genes were enriched in electric field existing UCW-MFC, accounting for the higher degradation efficiency. In conclusion, this study provided an effective strategy for removing antibiotics and ARGs in wastewater by operating a BER-UCW-MFC coupled system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The prognosis in cases of pancreatic ductal adenocarcinoma (PDAC) with current treatment modalities is poor owing to the highly desmoplastic tumor microenvironment (TME). Herein, a β-glucans-functionalized zinc-doxorubicin nanoparticle system (βGlus-ZnD NPs) that can be orally administered, is developed for targeted PDAC therapy. Following oral administration in PDAC-bearing mice, βGlus-ZnD NPs actively target/transpass microfold cells, overcome the intestinal epithelial barrier, and then undergo subsequent phagocytosis by endogenous macrophages (βGlus-ZnD@Mϕ). As hitchhiking cellular vehicles, βGlus-ZnD@Mϕ transits through the intestinal lymphatic system and enters systemic circulation, ultimately accumulating in the tumor tissue as a result of the tumor-homing and "stealth" properties that are conferred by endogenous Mϕ. Meanwhile, the Mϕ that hitchhikes βGlus-ZnD NPs is activated to produce matrix metalloproteinases, destroying the desmoplastic stromal barrier, and differentiates toward the M 1 -like phenotype, modulating the TME and recruiting effector T cells, ultimately inducing apoptosis of the tumor cells. The combination of βGlus-ZnD@Mϕ and immune checkpoint blockade effectively inhibits the growth of the primary tumor and suppresses the development of metastasis. It thus represents an appealing approach to targeted PDAC therapy., (© 2023 Wiley-VCH GmbH.)

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10 -11 ). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3 . Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10 -4 ), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

Aroma is an important attribute of infant formula (IF). In this study, 218 volatiles and 62 odor-active compounds were detected from IF by dynamic headspace sampling combined with comprehensive 2-dimensional gas chromatography-olfactometry-mass spectrometry. Aldehydes and ketones were determined as the most abundant odor-active compounds. Among them, the contents of pentanal and hexanal were the most abundant, while 1-octen-3-one had the highest flavor dilution factor and odor activity value in most of the IF. Sensory evaluation and electronic nose analysis showed that the skimming process, the fatty acid composition, and powdered or liquid milk base used for the production of IF may be important factors resulting in their differences in aroma profiles and compounds. These differences were assumed to be mainly ascribed to the Maillard reaction and lipid oxidation, which were largely influenced by the temperature and water activity., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 ( JAG1 ) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population. Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1 a and jag1b in biliary development were examined by morpholino knockdown in zebrafish. Results: Single nucleotide polymorphisms rs6077861 [ P Allelic = 1.74 × 10 -4 , odds ratio = 1.78, 95% confidence interval: 1.31-2.40] and rs3748478 ( P Allelic = 5.77 × 10 -4 , odds ratio = 1.39, 95% confidence interval: 1.15-1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model. Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Pei, Zhou, Song, Pan, Gong, Wu, Yu, Cui, Gu, Chu and Cai.)

The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide 275VQIINK280 of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies, including AD. However, the mechanism that links tau acetylated on lysine 280 (tau-acK280) to subsequent progression to neurodegenerative disease remains unclear. Here, we demonstrate that tau-acK280 is critical for tau propagation processes including secretion, aggregation, and seeding. We developed an antibody, Y01, that specifically targets tau-acK280 and solved the crystal structure of Y01 in complex with an acK280 peptide. The structure confirmed that Y01 directly recognizes acK280 and the surrounding residues. Strikingly, upon interaction with acetylated tau aggregates, Y01 prevented tauopathy progression and increased neuronal viability in neuron cultures and in tau-Tg mice through antibody-mediated neutralization and phagocytosis, respectively. Based on our observations that tau-acK280 is a core species involved in seeding and propagation activities, the Y01 antibody that specifically recognizes acK280 represents a promising therapeutic candidate for AD and other neurodegenerative diseases associated with tauopathy.

Tetracycline in wastewater can pose adverse impacts on the environment and human health. Forward osmosis (FO) is a promising method to reject antibiotics due to its low energy demand and high rejection rate. Tetracycline rejection during FO is a complicated process. Mechanistic models have been developed to describe antibiotic rejection by the FO membrane under ideal conditions but cannot be applied to real wastewater. Herein, the effects of draw concentration, pH, and solute type on the fate of tetracycline during FO were investigated by combining experimentation, factor analysis, and artificial neural network (ANN) modeling. High draw concentrations led to high convection that favored tetracycline diffusion. Low draw pH helped reject antibiotics potentially due to the decreased tortuosity and pore size of the FO membrane. When different draw solutes were tested, both convection and electrostatic interaction exerted effects on tetracycline retention on the FO membrane surface, and steric hindrance could further affect the amount of tetracycline in the draw solution. Exploratory factor analysis (EFA) showed that tetracycline rejection was a combined result of convection, steric hindrance, and electrostatic interactions. Path analysis revealed the significant roles of initial conductivity and draw pH in tetracycline rejection. Eight representative input variables were selected from 13 observed explanatory variables using redundancy analysis (RDA), based on which an ANN was trained and successfully predicted tetracycline diffusion and transfer through the FO membrane. These results have provided practical and predictive insights in the development of FO processes for efficient treatment of pharmaceutical wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lymphadenopathy with increased immunoglobulin (Ig) G4 + plasma cells can be a nonspecific finding or a manifestation of immunoglobulin G4-related disease (IgG4-RD). It remains unclear whether there are characteristic pathologic features of IgG4-RD involving lymph nodes, or if IgG4-RD lymphadenopathy can occur without other manifestations of IgG4-RD. In this study, we assessed 55 lymph node biopsy specimens (44 men and 11 women with a mean age of 55 y) with increased IgG4 + plasma cells that had 1 of the 6 well-described pathologic patterns. We also correlated these findings with IgG4 serum levels and followed these patients for 7 to 108 months (mean, 34.9 mo) for the occurrence of extranodal IgG4-RD. We further compared lymphadenopathy in patients who developed other manifestations of IgG4-RD (RD + , n=20, 36%) versus those who did not (RD - , n=35, 64%). We found that there were only minor significant differences between 2 groups, including frequency of receiving treatment (RD + , 90% vs. RD - , 60%, P =0.021) and higher serum levels of C-reactive protein (>8 mg/L, RD + , 53% vs. RD - , 13%, P =0.007). Other differences were either borderline or not significant, including mean age (RD + , 59.8 y vs. RD - , 51.9 y, P =0.097), male-to-female ratio (RD + , 16:4 vs. RD - , 28:7, P =1), constitutional symptoms (RD + , 25% vs. RD - , 9%, P =0.096), multiple enlarged lymph nodes (RD + , 45% vs. RD - , 26%, P =0.143), good response to therapy (RD + , 94% vs. RD - , 94%, P =1); higher serum IgG4 levels (>280 mg/dL, RD + , 75% vs. RD - , 51%, P =0.086), anemia (RD + , 45% vs. RD - , 43%, P =0.877), leukopenia (RD + , 0% vs. RD - , 3%, P =0.446), thrombocytopenia (RD + , 10% vs. RD - , 6%, P =0.556), positivity for antinuclear antibody (RD + , 24% vs. RD - , 29%, P =0.688), elevated serum levels of lactate dehydrogenase (>225 U/L, RD + , 0% vs. RD - , 20%, P =0.064), elevated serum IgE level (>100 IU/mL, RD + , 75% vs. RD - , 92%, P =0.238), and hypergammaglobulinemia (RD + , 90% vs. RD - , 86%, P =0.754). There were also no differences in morphologic patterns ( P =0.466), IgG4 + cell location ( P =0.104), eosinophil counts (RD + , 10.3±11.3 vs. RD - , 13.4±17.5, P =0.496), Epstein-Barr virus positivity (RD + , 35% vs. RD - , 60%, P =0.074), and Epstein-Barr virus-positive cell location ( P =0.351). Our findings suggest that there are minimal differences between stringently defined IgG4-RD lymphadenopathy with versus without other manifestations of IgG4-RD. These findings also suggest the existence of IgG4-RD lymphadenopathy as the sole presentation of IgG4-RD., Competing Interests: Conflicts of Interest and Source of Funding: Supported by grants from the Ministry of Science and Technology, Taiwan (MOST 109-2320-B-006-045-MY3) to K.-C.C. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Apis laboriosa is the largest honeybee that lives mainly on cliff faces, with strong migratory ability. In this study, we firstly sequenced and assembled two complete mitochondrial genomes of A. laboriosa isolated from two distant locations in China (Chongqing and Shangri-La regions). Combined with the published mitochondrial genome of A. laboriosa from Nepal, comparative genomic analyses were conducted to gain insight into the genetic diversity of giant honeybees from different geographical distributions. The mitochondrial genomes of A. laboriosa from Chongqing and Shangri-La regions were 15,579 and 15,683 bp in length, respectively, both larger than that from Nepal with the length of 15,510 bp. Three mitochondrial genomes all harbor 37 common genes and present the same AT bias and the frequency of codon usage. However, the fragments including COX 1, SSUrRNA, LSUrRNA, and the AT-rich region of the mitochondrial genome from Shangri-La region demonstrate distinctive insertions and deletions compared to those from Chongqing and Nepal regions. Phylogenetic trees of mitochondrial genomes show that A. laboriosa from Chongqing is most closely related to that from Nepal, rather than to Shangri-La. Genetic distance between Shangri-La and Chongqing or Nepal was even larger than that between the various subspecies of Apis mellifera . Overall, these results unmark that A. laboriosa in different geographical distributions can exhibit high genetic diversity at the mitochondrial genomic level, and therein, A. laboriosa from Shangri-La may be the subspecies. All these studies will contribute to our understanding of the geographical distribution and genetic differentiation of black giant honeybee in Asian region., Competing Interests: We certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Wheat plants are ubiquitously simultaneously exposed to salinity and limited iron availability caused by soil saline-alkalisation. Through this study, we found that both low Fe and NaCl severely inhibited the growth of seminal roots in wheat seedlings; however, sufficient Fe caused greater growth cessation of seminal roots than low Fe under salt stress. Low Fe improved the root meristematic division activity, not altering the mature cell sizes compared with sufficient Fe under salt stress. Foliar Fe spray and split-root experiments showed that low Fe-alleviating the salinity-induced growth cessation of seminal roots was dependent on local low Fe signals in the roots. Ionomics combined with TEM/X-ray few differences in the root Na + uptake and vacuolar Na + sequestration between two Fe levels under salt stress. Phytohormone profiling and metabolomics revealed salinity-induced overaccumulation of ACC/ethylene and tryptophan/auxin in the roots under sufficient Fe than under low Fe. Differential gene expression, pharmacological inhibitor addition and the root growth performance of transgenic wheat plants revealed that the rootward auxin efflux and was responsible for the low Fe-mediated amelioration of the salinity-induced growth cessation of seminal roots. Our findings will provide novel insights into the modulation of crop root growth under salt stress., (© 2022 John Wiley & Sons Ltd.)

Current in the milliampere range can be used for electrochemical inactivation of bacteria. Yet, bacteria-including antibiotic resistant bacteria (ARB) may be subjected to sublethal conditions due to imperfect mixing or energy savings measures during electrochemical disinfection. It is not known whether such sublethal current intensities have the potential to stimulate plasmid transfer from ARB. In this study, conjugal transfer of plasmid pKJK5 was investigated between Pseudomonas putida strains under conditions reflecting electrochemical disinfection. Although the abundance of culturable and membrane-intact donor and recipient cells decreased with applied current (0-60 mA), both transconjugant density and transconjugant frequency increased. Both active chlorine and superoxide radicals were generated electrolytically, and ROS generation was induced. In addition, we detected significant over expression of a core oxidative stress defense gene (ahpCF) with current. Expression of selected conjugation related genes (traE, traI, trbJ, and trbL) also significantly correlated with current intensity. ROS accumulation, SOS response and subsequent derepression of conjugation are therefore the plausible consequence of sublethal current exposure. These findings suggest that sublethal intensities of current can enhance conjugal plasmid transfer, and that it is essential that conditions of electrochemical disinfection (applied voltage, current density, time and mixing) are carefully controlled to avoid conjugal ARG transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Zero-waste biochar is an emerging tool for carbon neutralization, but the role of biochar in reducing greenhouse gases (GHGs) emissions from CWs were controversy and uncertainty. Yet, no previous study has integrated multiple research systems to quantitatively examine biochar-mediated GHGs emission reduction potential in CWs. Here we synthesized 114 studies to quantify biochar-induced declines ability of GHGs in the CWs by using the multi-level meta-analysis, reveal the variation of GHGs emission effect in different biochar-CWs and its response relationship with biochar, and identify the moderating variables that had a strong explanatory effect on the emission reduction effect of biochar. We showed that biochar remarkably affect CO 2 mitigation (p < 0.05), but has insignificant and heterogeneous effects on CH 4 and N 2 O. Pyrolysis time, influent dissolved oxygen (DO), influent NO 3 - -N concentration, hydraulic retention time (HRT) and wetland type can significantly affect the effect of biochar on CH 4 emission reduction. Particularly, the importance of HRT and wetland type was 0.89 and 0.85, respectively. Specially, the surface batch CWs modified by biochar could significantly promote the emission of CH 4 (p < 0.001), and the effect size was up to 89.59. For N 2 O, biochar diameter, biochar addition ratio, influent COD/TN ratio, plant name, and removal efficiency of NO 3 - -N/TN/COD were significant moderators. Among them, influent COD/TN ratio and plant name showed a stronger explanation. Planting Cyperus alternifolius L. significantly enhanced the N 2 O emission reduction capacity by biochar (p < 0.001), and effect size was as low as -24.32. 700-900 °C biochar can promote CH 4 flux but inhibit N 2 O flux. This study provides an important theoretical basis and valuable strategic guidance for more accurate estimation and improvement of synergistic emission reduction benefits between CH 4 and N 2 O of biochar in CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed ( Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR , GLK , NIGT1/HRS1/HHO , KAN , and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis -acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs . Further, 29 putative miRNAs were identified to be targeting BnaGARPs . Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases., Materials and Methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018., Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time., Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Zhou, Sun, Li, Liu, Song, Yang, Teng, Wei and Xu.)

Osteoarthritis (OA) is considered to be a highly heterogeneous disease with progressive cartilage loss, subchondral bone remodeling, and low-grade inflammation. It is one of the world's leading causes of disability. Most conventional clinical treatments for OA are palliative drugs, which cannot fundamentally cure this disease. The stromal vascular fraction (SVF) from adipose tissues is a heterogeneous cell population. According to previous studies, it contains a large number of mesenchymal stem cells, which have been used to treat OA with good therapeutic results. This safe, simple, and effective therapy is expected to be applied and promoted in the future. In this paper, the detailed pathogenesis, diagnosis, and current clinical treatments for OA are introduced. Then, clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Insufficient nitrogen removal is a key challenge for the application of an osmotic membrane bioreactor (OMBR). The integration of a bioelectrochemical system (BES) and an OMBR was constructed to enhance nitrogen removal.To optimize the operation, five aeration intensities and three draw solutes (DSs) were applied in the proposed system. The results showed that the proposed system obtained the highest nitrogen removal efficiency of 77.36 ± 3.55 % with an aeration intensity of 0.6 L/min, and it was further increased to 94.99 ± 2.83 % and 99.92 ± 0.14 %with the NaOAc DS and the glucose DS, respectively.The analysis ofmetabolic pathways implied that species interactions existed,andthe following different mechanisms of enhanced nitrogen removal for the two organic DSs were proposed. The growth of denitrifying bacteria was enhanced by using reverse-fluxed organic NaOAc DS as a carbon source;glucoseDS stimulated electron transfer system activity to accelerate denitrification., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Excessive consumption of sodium salt is one of the important inducers of cardiovascular and cerebrovascular diseases. The reduction of physical labor and attention to health make research on low-sodium salt imminent. Ultrafiltration, gel filtration, preparative high-performance liquid chromatography, and liquid chromatography with tandem mass spectrometry were employed for further purification and identification of the salty enhancing peptides in yeast extracts. Moreover, human transmembrane channel-like 4 (TMC4) was constructed and evaluated by computer-based methods, and salt-enhancing peptides were identified based on its allosteric sites. PN, NSE, NE and SPE were further determined to be salty enhancing peptides through sensory evaluation, and their taste mechanism was investigated. The results presented here suggest that silicon screening focused on TMC4 allosteric sites and sensory evaluation experiments can greatly increase the discoverability and identifiability of salty enhancer peptides, and this strategy is the first to be applied to the development of salty enhancer peptides., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Soil microbial fuel cells (MFCs) have been applied for the in situ remediation of soils polluted by single antibiotics. However, the investigation of only single antibiotic pollution has hindered MFC application in real-world soil remediation, where the effects of multiple antibiotics with similar chemical structures on the fate of antibiotics and their corresponding antibiotic resistance genes (ARGs) remain unknown. In this study, antibiotic removal rates, microbial community compositions, metabolite compositions, and ARG abundances were investigated in soil MFCs by adding two commonly used antibiotics (sulfadiazine, SDZ, and sulfamethoxazole, SMX), and comparing them with the addition of only a single antibiotic (SDZ). The antibiotic removal rate was higher in the soil MFC with addition of mixed antibiotics compared to the single antibiotic due to enhanced biodegradation efficiency in both the upper (57.24% of the initial antibiotic concentration) and lower layers (57.07% of the initial concentration) of the antibiotic-polluted soils. Bacterial community diversity in the mixed antibiotic conditions increased, and this likely resulted from the decreased toxicity of intermediates produced during antibiotic biodegradation. Moreover, the addition of mixed antibiotics led to lower risks of ARG release into soil environments, as reflected by higher abundances of host bacteria in the single antibiotic treatment. These results encourage the further development of soil MFC technology for in situ remediation of antibiotic-polluted soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The reconstruction of a large bone defect to an extent that exceeds its self-healing capacity has been a great clinical challenge. In pursuit of this goal, a biomaterial-based scaffold that comprises radially aligned mineralized collagen (RA-MC) fibers that incorporate nanosilicon (RA-MC/nSi), is proposed. The chemical composition of the MC fibers is similar to that of natural bone matrices. The therapeutic efficacy of the RA-MC/nSi scaffold is evaluated in a mouse model with an experimentally created large calvarial defect. In vitro and in vivo results reveal that the RA-MC fibers of the scaffold guide the directional infiltration and migration of reparative cells from the host tissue toward the center of the defect, suggesting a potential application in promoting osteoconductivity. The incorporated nSi renders the scaffold able sustainably to release gaseous hydrogen and water-soluble silicic acid during the healing process. The released hydrogen gas can effectively regulate redox homeostasis and mitigate excessive inflammation, and the silicic acid can promote the proliferation of reparative cells and enhance their osteogenic differentiation, indicative of osteoinductivity. These findings support the use of the as-proposed biomimetic RA-MC/nSi scaffold as a promising bone substitute to enhance the regeneration of large bone defects., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Diabetes mellitus (DM) is a global epidemic with increasing incidence, which results in diverse complications, seriously affects the patient quality of life, and brings huge economic burdens to society. Diabetic neuropathy is the most common chronic complication of DM, resulting in neuropathic pain and chronic itch. The precise mechanisms of diabetic neuropathy have not been fully clarified, hindering the exploration of novel therapies for diabetic neuropathy and its terrible symptoms such as diabetic pain and itch. Accumulating evidence suggests that neuroinflammation plays a critical role in the pathophysiologic process of neuropathic pain and chronic itch. Indeed, researchers have currently made significant progress in knowing the role of glial cells and the pro-inflammatory mediators produced from glial cells in the modulation of chronic pain and itch signal processing. Here, we provide an overview of the current understanding of neuroinflammation in contributing to the sensitization of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, we also summarize the inflammation mechanisms that contribute to the pathogenesis of diabetic itch, including activation of glial cells, oxidative stress, and pro-inflammatory factors. Targeting excessive neuroinflammation may provide potential and effective therapies for the treatment of chronic neuropathic pain and itch in DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fang, Wang, Song, Wang and Zhang.)

Considering conventional disinfection methods are not effective in simultaneously removing ARB and ARGs, a novel electrochemical disinfection (ED) process assisted by molybdenum carbide (Mo 2 C) electrodes was developed in this study. The established ED process was proved to effectively inactivate multi-resistant ARB (i.e. Escherichia coli K-12 LE392 with resistance to kanamycin, ampicillin, and tetracycline) and to degrade ARGs (including tetA and bla TEM in the form of both intracellular (iARGs) and extracellular ARGs (eARGs)). Specifically, within 15 min treatment by the Mo 2 C-assisted ED under 2.0 V, a 5-log ARB removal was realized, without any ARB regrowth observed, indicating a permanent inactivation of ARB by the process. Moreover, degradation of the iARGs (0.4-log reduction of the bla TEM and 3.1-log reduction of the tetA) and the eARGs (4.2-log reduction of the bla TEM and 1.1-log reduction of the tetA) were achieved within 60 min, further underpinning the viability of the Mo 2 C-based ED. While e - , H 2 O 2 , and •O 2 - played leading roles in the entire process of ED, H + and •OH contributed to bacterial inactivation in the early and late stages of ED, respectively. The reactive species induced by electrolysis posed pressure to the ARB strains, which enhanced oxidative stress response, triggered higher reactive oxygen species generation, induced membrane damage and changed cellular structure. Collectively, the Mo 2 C-assisted ED demonstrated in the present study represents an attractive alternative to the traditional disinfection methods in combating the spread of antibiotic resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microbial electrolysis cells (MECs) have been applied for antibiotic degradation but simultaneously induced antibiotic resistance genes (ARGs), thus representing a risk to disseminate antibiotic resistance. However, few studies were on the potential and risk of ARGs transmission in the MECs. This work assessed conjugative transfer of ARGs under three tested conditions (voltages, cell concentration, and donor/recipient ratio) in both single- and two-chamber MECs. The results indicated that voltages (> 0.9 V) facilitated the horizontal frequency of ARGs in the single-chamber MECs and anode chamber of two-chamber MECs. The donor cell number (donor/recipient ratio was 2:1) increased the transfer frequency of ARGs. Furthermore, voltages ranged from 0.9 to 2.5 V increased reactive oxygen species (ROS) production and cell membrane permeability in MECs. These findings offer new insights into the roles of ARG transfer under different applied voltages in the MECs, which should not be ignored for horizontal transfer of antibiotic resistance., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng . Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. We found that various doses of Rh2 intrathecal injection dose-dependently attenuated SNI-induced mechanical allodynia and thermal hyperalgesia. Rh2 also inhibited microglia and astrocyte activation in the spinal cord of a murine SNI model. Rh2 treatment inhibited SNI-induced increase of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. Expression of miRNA-21, an endogenous ligand of Toll like receptor (TLR)8 was also decreased. Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.

Antibiotics removal and ARGs control in microbial fuel cell (MFC) has received extensive attention. In particular, the critical role of bioelectrochemical characteristics deserves further study. Bioelectrochemical characteristics significantly affected sulfamethoxazole (SMX) removal and ARGs fate, in which the current intensity played a more critical role than anode potential. High-concentration SMX (2 mg/L and 10 mg/L) facilitated the anode potential tend to be close, and thus, the strengthening effect of current on the system was highlighted. However, the SMX degradation pathway under different bioelectrochemical characteristics was not affected. Furthermore, the higher current intensity was preferable to antibiotic removal, but unfavorable for ARGs control might be due to the oxidative stress on microorganisms. Low-concentration SMX (0.5 mg/L) contributed to improving higher electricity generation because of Geobacter enrichement. This study suggested that appropriate bioelectrochemical characteristics regulation in MFCs was essential in removing antibiotics and controlling ARGs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Microbial electrolysis cells (MECs) are widely considered as promising alternatives for degrading antibiotics. As one of the major operating parameters in MECs, voltage might affect the spread of antibiotic resistance genes (ARGs) given it can affect the physiological characteristics of bacteria. However, little is known about the impacts of voltage on the acceleration of bacterial mutation and the promotion of ARG dissemination via horizontal transfer in MECs. In this study, two voltages (0.9 V and 1.5 V) were applied to identify if electrical stimulation could increase bacterial mutation frequency. Three voltages (0.9 V, 1.5 V, and 2.5 V) were used to evaluate the conjugative transfer frequency of plasmid-encoded the ARGs from the donor (E. coli K-12) to the recipient (E. coli HB101) in MECs. After repeating subculture in MECs for 10 days, the mutation frequency of E. coli K-12 was promoted, consequently, the generated mutants became more resistant against tetracycline. When the voltage was higher than 0.9 V, conjugative ARG transfer frequency was significantly increased in the anode chamber (p < 0.05). The over-production of reactive oxygen species (ROS) (voltage >0.9 V) and cell membrane permeability (voltage >1.5 V) were significantly enhanced under electrical stimulations (p < 0.05). Genome-wide RNA sequencing indicated that the expressions of genes related to oxidative stress and cell membrane were upregulated with exposure to electrical stimulation. Electrical stimulations induced oxidative reactions, which triggered ROS over-production, SOS response, and enhancement of cell membrane permeability for both donor and recipient in the MECs. These findings provide insights into the potential role of voltage in the generation and spread of ARGs in MECs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)