Electrochemically Driven Nickel-Catalyzed Halogenation of Unsaturated Halide and Triflate Derivatives.

A robust electrochemically driven nickel-catalyzed halogen exchange of unsaturated halides and triflates (Br to Cl, I to Cl, I to Br, and OTf to Cl) is reported. A combination of NiCl2 ⋅ glyme as the precatalyst, 2,2'-bipyridine as a ligand, NMP as the solvent, and electrochemistry allowed the generation of a nickel species that promotes reductive elimination of the desired product. This paired electrochemical halogenation is compatible with a range of unsaturated halides and triflates, including heterocycles, dihaloarenes, and alkenes with good functional-group tolerance. Joint experimental and theoretical mechanistic investigations highlighted three catalytic events: i) oxidative addition of the aryl halide to a Ni(0) species to deliver a Ni(II) intermediate; ii) halide metathesis at Ni(II); iii) electrochemical oxidation of Ni(II) to Ni(III) to enable the formation of the desired aryl halide upon reductive elimination. This methodology allows the replacement of heavy halogens (I or Br) or polar atoms (O) with the corresponding lighter and more lipophilic Cl group to block undesired reactivity or modify the properties of drug and agrochemical candidates.

Effects of various coating methods on the mechanical, physical, and aesthetic properties of GUMMETAL® archwires: In vitro study.

PURPOSE: The objective of this study was to evaluate the mechanical, physical, and aesthetic properties of GUMMETAL® (GM) orthodontic archwires after the application of various aesthetic coating materials. METHODS: This in vitro study included 180 orthodontic wires: five experimental groups used 0.016×0.022-inch GM as the core-based wire followed by the application of epoxy, polytetrafluoroethylene (PTFE), clear ceramic, white ceramic, or silicone; and four control groups: 0.016×0.022-inch GM, 0.019×0.025-inch GM, 0.016×0.022-inch stainless steel (SS), and 0.019×0.025-inch SS. Frictional forces, force deflection rate, yield strength, aesthetic colour value, corrosive and wear resistance were compared between the experimental and control groups. RESULTS: Among the coated wires, white ceramic exhibited the highest frictional force (2.06±0.20 N) and silicone showed the lowest values (0.88±0.12 N). There were significant differences in static friction between experimental and control groups (P<0.001). PTFE coating had the highest force deflection rate (9.03±0.12 N/mm) and yield strength (10.0±0.14 N/mm) among coated wires and white ceramic exhibited the lowest values (6.86±0.14 N/mm and 7.74±0.17 N/mm for force deflection rate and yield strength, respectively). Differences in force deflection rate and yield strength between experimental and control groups were statistically significant (P<0.001). All coated wire groups had a clinical difference in colour when compared to A1 shade. Coated and uncoated wires showed good corrosion resistance after one week in corrosive saliva with no detectable loss of mass. CONCLUSIONS: This study has shown that coating wires can improve some aspects of the wire properties but not all when compared to uncoated GM and SS. Future investigation of the materials used in this study is required to further characterize their properties.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Short-term effects of wildfire on soil arthropods in a semi-arid grassland on the Loess Plateau.

Fires lead to dramatic shifts in ecosystems and have a large impact on the biota. Soil organisms, especially soil fauna, are often used as indicators of environmental change. At present, minimal attention has been paid to using soil fauna as an indicator of environmental change after a fire. Here, a field survey of burnt herbaceous vegetation in semi-arid areas was conducted to determine the response of soil arthropods to fire and their short-term recovery after fire. Overall, the abundance and biomass of soil arthropods was more sensitive to fire than the number of groups. The number of soil arthropod groups, especially the dominant groups (mites and springtails), was not significantly affected by wildfires. At the unburned site, soil arthropod abundance showed significant seasonal shifts that may be related to the vegetation properties, temperature, and precipitation caused by seasonal changes. In contrast, soil arthropods at the burnt sites showed a delayed recovery and had only reached 56%-82%, 17%-54%, and 91%-190% of the biomass in the unburnt forest at the 3, 6, and 9 months after the burning event. Our findings of soil arthropod abundance changes in the present study suggest that fire-induced changes in soil and vegetation properties (e.g., AN, LT, and VC) were crucial factors for the changes in soil arthropod abundance in this semi-arid grassland. We conclude that fire disturbance reduces the seasonal sensitivity of soil arthropods by altering their habitat. This study furthers our understanding of wildfire impact recovery by documenting the short-term temporal dynamics of soil arthropods.

Phylogenetic position and morphological polymorphism of the chafer, Clinterocera nigra (Coleoptera: Scarabaeidae: Cetoniinae) from Taiwan.

Three mitochondrial genomes of the cetoniine beetle, Clinterocera nigra (Kano, 1931) were assembled via next-generation sequencing. The newly sequenced mitogenomes all have 37 genes, showing standard gene order and annotation as the other insects. To examine their phylogenetic positions and relationships between their elytral color (red-spot and melanistic forms) and sequence variation, a total of 118 public mitogenomes of Scarabaeidae were used to infer a maximum-likelihood (ML) tree. Our results show that the melanistic form is grouped within red-spot ones, revealing a population level variation on the elytra color. Our work also provides the first mitogenomic reference of myrmecophilous chafers.

Luteolin Phosphate Derivatives Generated by Cultivating Bacillus subtilis var. Natto BCRC 80517 with Luteolin.

Luteolin (LUT), a plant-derived flavone, exhibits various bioactivities; however, the poor aqueous solubility hampers its applications. Here, we revealed bioconversion of LUT by Bacillus subtilis BCRC 80517, yielding three water-soluble phosphate conjugates. These derivatives were identified as luteolin 4'-O-phosphate (L4'P), luteolin 3'-O-phosphate (L3'P), and luteolin 7-O-phosphate (L7P) by LC-ESI-MS/MS and NMR. Besides, we found that Bacillus subtilis BCRC 80517 was able to convert different levels of LUT but showed a limited conversion rate. By observing bacterial morphology with transmission electron microscopy and confocal fluorescence microscopy, we found that LUT disrupted the bacterial membrane integrity, which explained the incomplete conversion. Additionally, we revealed a spontaneous intramolecular transesterification of L4'P to L3'P, the thermodynamically more stable form, under acidic conditions and proposed the possible mechanism involving a cyclic phosphate as the intermediate. This study provides insight into development of a potent structural modification strategy to enhance the solubility of LUT through biophosphorylation.

Furin and TMPRSS2 Resistant Spike Induces Robust Humoral and Cellular Immunity Against SARS-CoV-2 Lethal Infection.

An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8+ T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.

Complications associated with irradiated homologous costal cartilage use in rhinoplasty: A systematic review and meta-analysis.

BACKGROUND: The use of irradiated homologous costal cartilage (IHCC) as an alternative source of graft material for rhinoplasty remains controversial because of the risk of complications. Herein, we aimed to perform a comprehensive assessment of complications associated with IHCC use in rhinoplasty through a meta-analysis of published studies. METHODS: We searched the PubMed, Embase, and Cochrane Library databases to identify eligible published studies, and we evaluated the complication rates of IHCC use in rhinoplasty. Published studies meeting the inclusion criteria included clinical studies involving at least 10 patients and assessing at least 1 postoperative long-term complication of rhinoplasty. Two investigators independently extracted data from the included studies using a standardized form. Meta-analysis was performed using a random-effects model. The main outcomes were the rates of various complications, including the need for revision surgery. RESULTS: Ten studies involving a total of 959 patients were analyzed. The complication rates were 2.07% (95% confidence interval [CI], 0.80%-5.23%) for warping, 1.77% (95% CI, 1.10%-2.83%) for infection, 1.34% (95% CI, 0.34%-5.16%) for resorption, 2.13% (95% CI, 0.86%-5.19%) for displacement, 2.99% (95% CI, 1.24%-7.03%) for revision, 0.16% (95% CI, 0.01%-3.25%) for extrusion, and 2.04% (95% CI, 1.02%-4.02%) for avulsion. All the included trials had moderate-to-high methodological quality except for small sample sizes and subjectively reporting of some complications. CONCLUSIONS: The overall long-term complication rates associated with IHCC use in rhinoplasty were low. Revision and displacement were the most common complications at the one-year follow-up; surgeons should pay special attention to the risk of these complications. IHCC can serve as a reliable material for rhinoplasty and achieve good patient satisfaction.

N-Aryl and N-Alkyl Carbamates from 1 Atmosphere of CO2.

We have successfully isolated and characterized the zinc carbamate complex (phen)Zn(OAc)(OC(=O)NHPh) (1; phen=1,10-phenanthroline), formed as an intermediate during the Zn(OAc)2 /phen-catalyzed synthesis of organic carbamates from CO2 , amines, and the reusable reactant Si(OMe)4 . Density functional theory calculations revealed that the direct reaction of 1 with Si(OMe)4 proceeds via a five-coordinate silicon intermediate, forming organic carbamates. Based on these results, the catalytic system was improved by using Si(OMe)4 as the reaction solvent and additives like KOMe and KF, which promote the formation of the five-coordinated silicon species. This sustainable and effective method can be used to synthesize various N-aryl and N-alkyl carbamates, including industrially important polyurethane raw materials, starting from CO2 under atmospheric pressure.

Artificial intelligence in gastroenterology and hepatology: Status and challenges.

Originally proposed by John McCarthy in 1955, artificial intelligence (AI) has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images. Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology. This review will illustrate AI technology procedures for medical image analysis, including data processing, model establishment, and model validation. Furthermore, we will summarize AI applications in endoscopy, radiology, and pathology, such as detecting and evaluating lesions, facilitating treatment, and predicting treatment response and prognosis with excellent model performance. The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation, ethics and legal concerns, and the incomprehensibility of the output results. Therefore, doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.

Two complete mitochondrial genomes of Papilio butterflies obtained from historical specimens (Lepidoptera: Papilionidae).

Museum specimens are collected for education, exhibition, and various multiple scientific purposes. However, millions of specimens remain in their collection boxes for years without being analyzed. Historical specimens have been known to contain low-quality DNA; hence, it is difficult to utilize their sequence information in phylogenetic studies. However, recent advances in high-throughput sequencing (HTS) make these collections amenable to phylogenomic studies. In this study, two historical specimens (Papilio xuthus Linnaeus, 1767, and Papilio thoas Linnaeus, 1771) were sampled and DNA extracted for HTS via the Miseq platform. Two complete mitogenomes were assembled, even though the DNA quality of those specimens was highly fragmented, below 250 bp in length. The 37 genes of 60 mitogenomes were aligned and used for inferring the phylogenetic relationships of Papilioninae. These two newly sequenced mitogenomes are correctly grouped in the genus Papilio, and this result indicates that historical specimens show great potential for phylogenetic studies with HTS technology.

Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) sponges microRNA-124-3p to up-regulate phosphodiesterase 4B (PDE4B) to accelerate the progression of Parkinson's disease.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson's disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) -124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Novel biomarkers for the diagnosis and prognosis of gallbladder cancer.

Gallbladder cancer (GBC) is the most common form of biliary tract malignancy with a dismal prognosis. A poor outcome in patients with GBC is related to the aggressive nature of the tumor, delayed diagnosis, and a lack of reliable biomarkers and effective treatment. Therefore, early diagnosis and accurate disease assessment are crucial to prolonging the patient survival. Identification of novel prognostic and diagnostic biomarkers may help improve the early diagnostic rate and develop specific targeted treatments for patients with GBC. We herein review the novel biomarkers that may be associated with the diagnosis and prognosis in GBC and their potential clinical significance in the management of GBC.

Factors Affecting the Competence of Nursing Assistants in Taiwan Long-Term Care Institutions.

With the increasing number of people with disabilities caused by an aging global population, the need for long-term care is gradually increasing. Nursing assistants (NAs) are the primary providers of direct care services to older adults with disabilities, whose knowledge, skills, and beliefs affect the quality of care provided. This study aimed to investigate the influential factors affecting NAs' current competences. A total of 255 NAs' valid questionnaires were collected from 20 long-term care institutions in Taiwan through convenience sampling. The questionnaire comprised dimensions of demographics and care competence. The study results indicated that NAs had the greatest care competence in the domain of recognition of patient rights (4.64 ± 0.54 points). The multiple regression indicated that age, religion, job category, disability care experience, the receiving of performance bonuses, and the receiving of year-end bonuses significantly affected the level of care competence (p < 0.05). With the aforementioned findings, the results of this study serve as references for the government in employing long-term care NAs and developing management policies. Training programs for NAs should be developed to improve the quality of care provided to older adults with disabilities.

Laparoscopic surgery for early gallbladder carcinoma: A systematic review and meta-analysis.

BACKGROUND: There is a controversy as to whether laparoscopic surgery leads to a poor prognosis compared to the open approach for early gallbladder carcinoma (GBC). We hypothesized that the laparoscopic approach is an alternative for early GBC. AIM: To identify and evaluate the safety and feasibility of laparoscopic surgery in the treatment of early GBC. METHODS: A comprehensive search of online databases, including MEDLINE (PubMed), Cochrane libraries, and Web of Science, was performed to identify non-comparative studies reporting the outcomes of laparoscopic surgery and comparative studies involving laparoscopic surgery and open surgery in early GBC from January 2009 to October 2019. A fixed-effects meta-analysis was performed for 1- and 5-year overall survival and postoperative complications, while 3-year overall survival, operation time, blood loss, the number of lymph node dissected, and postoperative hospital stay were analyzed by random-effects models. RESULTS: The review identified 7 comparative studies and 8 non-comparative studies. 1068 patients (laparoscopic surgery: 613; open surgery: 455) were included in the meta-analysis of 1-, 3-, and 5-year overall survival with no significant differences observed [(HR = 0.54; 95%CI: 0.29-1.00; I 2 = 0.0%; P = 0.051), (HR = 0.75; 95%CI: 0.34-1.65; I 2 = 60.7%; P = 0.474), (HR = 0.71; 95%CI: 0.47-1.08; I 2 = 49.6%; P = 0.107), respectively]. There were no significant differences in operation time [weighted mean difference (WMD) = 18.69; 95%CI: -19.98-57.36; I 2 = 81.4%; P = 0.343], intraoperative blood loss (WMD = -169.14; 95%CI: -377.86-39.57; I 2 = 89.5%; P = 0.112), the number of lymph nodes resected (WMD = 0.12; 95%CI: -2.95-3.18; I 2 = 73.4%; P = 0.940), and the complication rate (OR = 0.69; 95%CI: 0.30-1.58; I 2 = 0.0%; P = 0.377 ) between the two groups, while patients who underwent laparoscopic surgery had a reduced length of hospital stay (WMD = -5.09; 95%CI: -8.74- -1.45; I 2 = 91.0%; P= 0.006). CONCLUSION: This systematic review and meta-analysis confirms that laparoscopic surgery is a safe and feasible alternative to open surgery with comparable survival and operation-related outcomes for early GBC.

Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma.

BACKGROUND: Despite significant advances in multimodality treatments, hepatocellular carcinoma (HCC) remains one of the most common malignant tumors. Identification of novel prognostic biomarkers and molecular targets is urgently needed. AIM: To identify potential key genes associated with tumor microenvironments and the prognosis of HCC. METHODS: The infiltration levels of immune cells and stromal cells were calculated and quantified based on the ESTIMATE algorithm. Differentially expressed genes (DEGs) between high and low groups according to immune or stromal scores were screened using the gene expression profile of HCC patients in The Cancer Genome Atlas and were further linked to the prognosis of HCC. These genes were validated in four independent HCC cohorts. Survival-related key genes were identified by a LASSO Cox regression model. RESULTS: HCC patients with a high immune/stromal score had better survival benefits than patients with a low score. A total of 899 DEGs were identified and found to be involved in immune responses and extracellular matrices, 147 of which were associated with overall survival. Subsequently, 52 of 147 survival-related DEGs were validated in additional cohorts. Finally, ten key genes (STSL2, TMC5, DOK5, RASGRP2, NLRC3, KLRB1, CD5L, CFHR3, ADH1C, and UGT2B15) were selected and used to construct a prognostic gene signature, which presented a good performance in predicting overall survival. CONCLUSION: This study extracted a list of genes associated with tumor microenvironments and the prognosis of HCC, thereby providing several valuable directions for the prognostic prediction and molecular targeted therapy of HCC in the future.

Prognostic factors and predictors of postoperative adjuvant transcatheter arterial chemoembolization benefit in patients with resected hepatocellular carcinoma.

BACKGROUND: Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) has improved overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the prognostic and predictive factors remain unclear. AIM: To assess the prognostic factors and the predictors of PA-TACE benefit for OS in patients with resected HCC. METHODS: Univariate and multivariate analyses were performed to identify the potential prognostic factors for OS. In order to assess the predictive factors of PA-TACE benefit, the interaction variables between treatments for each subgroup were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 378 patients (PA-TACE vs surgery alone, 189:189) from three centers were included after a propensity-score 1:1 matching analysis. Compared to the group receiving surgery alone, PA-TACE prolonged the OS rate in patients with resected HCC (P < 0.001). The Barcelona Clinic Liver Cancer system and ferritin-to-hemoglobin ratio (FHR) were used as the prognostic factors for OS in both groups. Age (P = 0.023) and microscopic vascular invasion (MVI) (P = 0.002) were also identified in the PA-TACE group, while gender (P = 0.027), hepatitis B virus (P = 0.034) and albumin-bilirubin grade (P = 0.027) were also selected in the surgery alone group. In addition, PA-TACE resulted in longer OS than surgery alone across subgroups [all hazard ratios (PA-TACE-to-surgery alone) < 1]. Notably, a significantly prolonged OS following PA-TACE was observed in patients with high FHR (P = 0.038) and without MVI (P = 0.048). CONCLUSION: FHR and Barcelona Clinic Liver Cancer stages were regarded as prognostic factors for OS. Moreover, high FHR and the absence of MVI were important predictive factors, which can be used to assist clinicians in selecting which patients could achieve a better OS with PA-TACE.

PP4 deficiency leads to DNA replication stress that impairs immunoglobulin class switch efficiency.

The serine/threonine phosphatase PP4 has been implicated in DNA damage repair and cell cycle regulation through its dephosphorylation of specific substrates. We previously showed that PP4 is required for mouse B cell development, germinal center (GC) formation and immunoglobulin (Ig) class switch recombination (CSR). Here, we investigate the mechanisms underlying this requirement and demonstrate that murine PP4-deficient B lymphocytes have a defect in cell proliferation. Strikingly, the DNA damage response pathway that involves ATM/p53 and is linked to cell cycle arrest and impaired cell survival is strongly induced in these mutant B cells. In response to LPS + IL-4, stimuli that trigger IgG1 production, these PP4-deficient B cells show inefficient phosphorylation of ATR, leading to reduced retention of γH2AX-NBS1 complexes at sites of DNA damage, and compromised switching to IgG1. However, beyond the cell proliferation phase, conditional deletion of PP4 under the control of AID/cre completely restores normal IgG1 production in mutant B cell cultures. In vivo, co-deletion of PP4 and p53 by AID/cre partially rescues switching to IgG1 in B cells of mice immunized with TNP-KLH. Our findings establish that PP4 is indispensable for preventing DNA replication stress that could interfere with CSR, thereby promoting antibody switching during the humoral immune response.

Laparoscopic repair via the transabdominal preperitoneal procedure for bilateral lumbar hernia: Three cases report and review of literature.

A lumbar hernia is a rare entity, and a bilateral lumbar hernia is much rarer. From May 2015 to October 2017, we treated only three patients with bilateral lumbar hernias. One patient came to the hospital presenting with right-sided abdominal pain, and the other two patients presented with bilateral lumbar masses. The previous bilateral lumbar hernia reported in the literature was repaired by open surgery. The laparoscopic approach via the transabdominal preperitoneal (TAPP) procedure with the self-gripping Parietex ProGrip™ mesh was performed at our center. The laparoscopic repair was conducted by a skilled hernia surgeon, and was successfully performed in the three patients. The patients resumed a semi-liquid diet and had no activity restriction after six hours following the operation. No antibiotics were used after the surgery. The operative times of the three patients were 120 min, 85 min, and 130 min. The blood loss volumes of the three patients were 20 mL, 5 mL, and 5 mL. The visual analogue scale pain scores of the three patients were 1, 2, and 2 on postoperative day 1, and were 1, 2, and 1 on postoperative day 3. No perioperative complications, such as bulge, wound infection and hematoma, occurred after the surgery. All of the patients were discharged on the third day after the operation. There was no chronic pain and no hernia recurrence during the follow-up. This study showed that the laparoscopic TAPP approach with the self-gripping mesh is safe and feasible, and can be considered an alternative method for the treatment of bilateral lumbar hernias.

DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation.

Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/-), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6-/- T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6-/- T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6-/- T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6-/- TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.