Corrigendum: Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.

[This corrects the article DOI: 10.3389/fmicb.2023.1212582.].

Bisphosphonates and Their Connection to Dental Procedures: Exploring Bisphosphonate-Related Osteonecrosis of the Jaws.

Bisphosphonates are widely used to treat osteoporosis and malignant tumors due to their effectiveness in increasing bone density and inhibiting bone resorption. However, their association with bisphosphonate-related osteonecrosis of the jaws (BRONJ) following invasive dental procedures poses a significant challenge. This review explores the functions, mechanisms, and side effects of bisphosphonates, emphasizing their impact on dental procedures. Dental patients receiving bisphosphonate treatment are at higher risk of BRONJ, necessitating dentists' awareness of these risks. Topical bisphosphonate applications enhance dental implant success, by promoting osseointegration and preventing osteoclast apoptosis, and is effective in periodontal treatment. Yet, systemic administration (intravenous or intraoral) significantly increases the risk of BRONJ following dental procedures, particularly in inflamed conditions. Prevention and management of BRONJ involve maintaining oral health, considering alternative treatments, and careful pre-operative and post-operative follow-ups. Future research could focus on finding bisphosphonate alternatives with fewer side effects or developing combinations that reduce BRONJ risk. This review underscores the need for further exploration of bisphosphonates and their implications in dental procedures.

Unraveling the interplay between norovirus infection, gut microbiota, and novel antiviral approaches: a comprehensive review.

Norovirus infection is a leading cause of acute gastroenteritis worldwide and can also cause harmful chronic infections in individuals with weakened immune systems. The role of the gut microbiota in the interactions between the host and noroviruses has been extensively studied. While most past studies were conducted in vitro or focused on murine noroviruses, recent research has expanded to human noroviruses using in vivo or ex vivo human intestinal enteroids culture studies. The gut microbiota has been observed to have both promoting and inhibiting effects on human noroviruses. Understanding the interaction between noroviruses and the gut microbiota or probiotics is crucial for studying the pathogenesis of norovirus infection and its potential implications, including probiotics and vaccines for infection control. Recently, several clinical trials of probiotics and norovirus vaccines have also been published. Therefore, in this review, we discuss the current understanding and recent updates on the interactions between noroviruses and gut microbiota, including the impact of norovirus on the microbiota profile, pro-viral and antiviral effects of microbiota on norovirus infection, the use of probiotics for treating norovirus infections, and human norovirus vaccine development.

Novel cancer treatment paradigm targeting hypoxia-induced factor in conjunction with current therapies to overcome resistance.

Chemotherapy, radiotherapy, targeted therapy, and immunotherapy are established cancer treatment modalities that are widely used due to their demonstrated efficacy against tumors and favorable safety profiles or tolerability. Nevertheless, treatment resistance continues to be one of the most pressing unsolved conundrums in cancer treatment. Hypoxia-inducible factors (HIFs) are a family of transcription factors that regulate cellular responses to hypoxia by activating genes involved in various adaptations, including erythropoiesis, glucose metabolism, angiogenesis, cell proliferation, and apoptosis. Despite this critical function, overexpression of HIFs has been observed in numerous cancers, leading to resistance to therapy and disease progression. In recent years, much effort has been poured into developing innovative cancer treatments that target the HIF pathway. Combining HIF inhibitors with current cancer therapies to increase anti-tumor activity and diminish treatment resistance is one strategy for combating therapeutic resistance. This review focuses on how HIF inhibitors could be applied in conjunction with current cancer treatments, including those now being evaluated in clinical trials, to usher in a new era of cancer therapy.

Analgesic Effects of Regional Analgesic Techniques in Pediatric Inguinal Surgeries: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Various regional analgesic techniques have been used in pediatric inguinal surgery to facilitate postoperative recovery. However, each technique's relative performance was undetermined owing to the lack of quantitative analysis. METHODS: We systematically searched MEDLINE, Cochrane Library, EMBASE, and Web of Science for randomized controlled trials that compared regional analgesia in pediatric inguinal surgeries. After critical study screening and selection, a random-effects network meta-analysis was performed. The primary outcome was the time to the first rescue analgesic after surgery, and the secondary outcomes were the number of patients requiring rescue analgesics after surgery, postoperative pain scores, incidence of postoperative nausea and vomiting, and other adverse events. RESULTS: This network meta-analysis included 69 randomized controlled trials (4636 patients) that compared 10 regional analgesic techniques. Our study revealed that the quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic after pediatric inguinal surgeries, by 7.7 hours (95% confidence interval [CI], 5.0-10.3) and 6.0 hours (95% CI, 3.9-8.2) when compared with the control group, respectively. In the subgroup involving only inguinal hernia repair, the quadratus lumborum block significantly prolonged the time to the first rescue analgesic than all other regional analgesics. In contrast, in the subgroup involving orchidopexies, only the caudal block significantly prolonged the time to the first rescue analgesic when compared with the control group (4.1 hours; 95% CI, 0.7-7.5). Wound infiltration and landmark-based ilioinguinal-iliohypogastric block had relatively poor analgesic effects than other regional analgesics. No serious adverse effects related to the regional analgesic techniques were reported in any of the included studies. CONCLUSIONS: The quadratus lumborum and transversus abdominis plane blocks had the longest time to the first rescue analgesic and the least rescue analgesic requirement for pediatric inguinal surgeries. Specifically, the quadratus lumborum block had the longest analgesic duration in inguinal hernia repair, and the caudal block was found to be the only regional analgesia that extended the time to the first rescue analgesic in pediatric orchidopexy. Most included randomized controlled trials had some concern or a high risk of bias, and future studies should focus on providing high-quality evidence to further clarify the analgesic effects of regional analgesia for pediatric inguinal surgeries.

Comparison of the Efficacy of Single-Injection Regional Analgesia Techniques for Total Abdominal Hysterectomy: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Single-injection regional analgesia techniques can provide effective analgesia for abdominal hysterectomy. However, few randomized controlled trials (RCTs) have directly compared these techniques for total abdominal hysterectomy (TAH), and the best strategy remains unknown. OBJECTIVES: In this network meta-analysis, we compared the analgesic efficacy of single-injection regional analgesia techniques in patients who underwent TAH. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: We searched the PubMed, Embase, Cochrane, and CINAHL databases for relevant trials from inception until April 2022. RCTs that examined single-injection regional analgesia techniques for TAH were included. Random-effects network meta-analyses were performed using the frequentist approach. The primary outcome was 24-hour cumulative morphine equivalent consumption. The secondary outcomes were pain scores, time to first request for rescue analgesia, and rates of postoperative nausea and vomiting (PONV). RESULTS: In total, 36 RCTs were included. Network meta-analyses indicated that the erector spinae plane block provided superior analgesia in terms of reduced morphine consumption, low PONV incidence, and longer time to first analgesia request. Moreover, compared with control (i.e., sham or placebo), the quadratus lumborum block provided superior analgesia in terms of time to first analgesia request and resting pain scores. LIMITATIONS: (1) Few studies have examined single-injection regional analgesia techniques other than the transversus abdominis plane block (TAPB) and wound infiltration, leading to a few indirect effect estimates. (2) Heterogeneity existed due to analgesic type/dose, plane block timing, and injection site. (3) Objective outcomes, such as length of hospital stay, were lacking; most studies only included the patient-reported subjective pain score. CONCLUSION: Single-injection blocks are effective analgesic techniques for TAH. Among them, the erector spinae plane block and quadratus lumborum block seem to have superior effects. Further studies should evaluate techniques other than TAPB and wound infiltration to draw definitive conclusions.

Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis.

PURPOSE: According to criteria recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), we analyzed the effects of branched-chain amino acid (BCAA)-rich supplements on muscle strength, muscle mass, and physical performance in older people. METHODS: We searched PubMed, Embase, Cochrane Library, and CINAHL from inception until March 2021. Randomized controlled trials that examined the effect of BCAA-rich supplements on older people were included. Random-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were stratified by participant and supplementation characteristics. Meta-regression analyses were performed to examine the effect of continuous variables. RESULTS: Thirty-five studies were included in this meta-analysis. Quality assessment revealed that 14 of 35 RCTs had some potential bias. The overall standardized mean difference (SMD) in muscle strength, muscle mass, and physical performance between the supplement and control groups was 0.35 (95% CI = [0.15, 0.55], P = 0.0007), 0.25 (95% CI = [0.10, 0.40], P = 0.0008), and 0.29 (95% CI = [0.00, 0.57], P = 0.05), respectively. Subgroup analysis revealed that essential amino acid supplementation improved handgrip strength more significantly than whey protein supplementation in older people. Meta-regression analysis revealed a significant linear relationship between improvements in handgrip strength and body mass index. CONCLUSIONS: BCAA-rich supplementation by older people may have beneficial effects on muscle mass and strength. However, the included studies had high heterogeneity, and the results must be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42020206674.

DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics.

Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (DHA-PLs) in physiology. Here, we investigated the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) triggered by RhoA inhibition-associated cell spreading. Lipidomic analyses showed that human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet undergo a 6-fold enrichment in DHA-PLs at the plasma membrane (PM) at the expense of monounsaturated oleic acid-containing PLs (OA-PLs). Consequently, DHA-PL enrichment at the PM induces a reduction in cell thickness and shifts cellular membranes towards a permissive mode of membrane fusion for transcellular tunnel initiation. We provide evidence that a global homeostatic control of membrane tension and cell cortex rigidity minimizes overall changes of TEM area through a decrease of TEM size and lifetime. Conversely, low DHA-PL levels at the PM lead to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PL levels in membranes affect cell biomechanical properties.

The impact of biomechanics on corneal endothelium tissue engineering.

The integrity of innermost layer of the cornea, the corneal endothelium, is key to sustaining corneal transparency. Therefore, disease or injury causing loss or damage to the corneal endothelial cell population may threaten vision. Transplantation of corneal tissue is the standard treatment used to replace malfunctioning corneal endothelial cells. However, this surgery is dependent upon donor tissue, which is limited in supply. Hence, tissue engineers have attempted to construct alternative transplantable tissues or cell therapies to alleviate this problem. Nevertheless, the intrinsic non-dividing nature of corneal endothelial cells continues to foil scientists in their attempts to yield large numbers of cells in the laboratory for use in such novel therapies. Interestingly, the contribution of the biomechanical properties of the underlying extracellular matrix (ECM) on cell division, tissue development and maintenance has been extensively investigated in other many cell types. However, the impact of biomechanics on corneal endothelial cell behaviour is relatively unexplored. Here, we describe contemporary tissue engineering solutions aimed at circumventing donor tissue scarcity. We review the ECM structure and biomechanical features of corneal endothelial cells. We discuss the alterations of ECM in endothelial disease development and progression and point out the role of ECM in developing a tissue-engineered corneal endothelium. We highlight the main biomechanical cues, including topographical and mechanical features, that impact cellular behaviors. Finally, we discuss the influence of biomechanical cues on cell and tissue development, and how corneal endothelial cells response to individual biomechanical stimuli in tissue engineering, which have implications for designing an engineered endothelium and maintaining cell function.

Molecular and cellular dissection of the oxysterol-binding protein cycle through a fluorescent inhibitor.

ORPphilins are bioactive natural products that strongly and selectively inhibit the growth of some cancer cell lines and are proposed to target intracellular lipid-transfer proteins of the oxysterol-binding protein (OSBP) family. These conserved proteins exchange key lipids, such as cholesterol and phosphatidylinositol 4-phosphate (PI(4)P), between organelle membranes. Among ORPphilins, molecules of the schweinfurthin family interfere with intracellular lipid distribution and metabolism, but their functioning at the molecular level is poorly understood. We report here that cell line sensitivity to schweinfurthin G (SWG) is inversely proportional to cellular OSBP levels. By taking advantage of the intrinsic fluorescence of SWG, we followed its fate in cell cultures and show that its incorporation at the trans-Golgi network depends on cellular abundance of OSBP. Using in vitro membrane reconstitution systems and cellular imaging approaches, we also report that SWG inhibits specifically the lipid transfer activity of OSBP. As a consequence, post-Golgi trafficking, membrane cholesterol levels, and PI(4)P turnover were affected. Finally, using intermolecular FRET analysis, we demonstrate that SWG directly binds to the lipid-binding cavity of OSBP. Collectively these results describe SWG as a specific and intrinsically fluorescent pharmacological tool for dissecting OSBP properties at the cellular and molecular levels. Our findings indicate that SWG binds OSBP with nanomolar affinity, that this binding is sensitive to the membrane environment, and that SWG inhibits the OSBP-catalyzed lipid exchange cycle.

A case of palatine tonsillar metastasis of lung adenocarcinoma: A CARE-compliant article.

RATIONALE: Palatine tonsil is an extremely rare site for metastatic disease, accounting for 0.8% of malignant tonsillar neoplasms. To the best of our knowledge, this is the first report of metastatic adenocarcinoma in the tonsil treated with wide excision and targeted therapy, with no local recurrence 6 months postoperatively. PATIENT CONCERNS: A 75-year-old man presented hemoptysis and mild productive cough for 2 weeks. DIAGNOSES: Palatine tonsil metastasis from lung adenocarcinoma, pT2bN0M1b, stage IVA, was confirmed. INTERVENTIONS: Wide excision of primary lung tumor and metastatic tonsil carcinoma has been performed, and the patient was undergoing targeted therapy with the epidermal growth factor receptor inhibitor afatinib. OUTCOMES: There was no local recurrence in the oropharynx 6 months postoperatively. LESSONS: We aim at highlighting the importance of a thorough evaluation for suspicion of tonsillar enlargement, which might be a sign of a primary malignancy elsewhere.

ADP-ribosylation factor-like 4A interacts with Robo1 to promote cell migration by regulating Cdc42 activation.

Cell migration is a highly regulated event that is initiated by cell membrane protrusion and actin reorganization. Robo1, a single-pass transmembrane receptor, is crucial for neuronal guidance and cell migration. ADP-ribosylation factor (Arf)-like 4A (Arl4A), an Arf small GTPase, functions in cell morphology, cell migration, and actin cytoskeleton remodeling; however, the molecular mechanisms of Arl4A in cell migration are unclear. Here, we report that the binding of Arl4A to Robo1 modulates cell migration by promoting Cdc42 activation. We found that Arl4A interacts with Robo1 in a GTP-dependent manner and that the Robo1 amino acid residues 1394-1398 are required for this interaction. The Arl4A-Robo1 interaction is essential for Arl4A-induced cell migration and Cdc42 activation but not for the plasma membrane localization of Robo1. In addition, we show that the binding of Arl4A to Robo1 decreases the association of Robo1 with the Cdc42 GTPase-activating protein srGAP1. Furthermore, Slit2/Robo1 binding down-regulates the Arl4A-Robo1 interaction in vivo, thus attenuating Cdc42-mediated cell migration. Therefore, our study reveals a novel mechanism by which Arl4A participates in Slit2/Robo1 signaling to modulate cell motility by regulating Cdc42 activity.

Ezrin enrichment on curved membranes requires a specific conformation or interaction with a curvature-sensitive partner.

One challenge in cell biology is to decipher the biophysical mechanisms governing protein enrichment on curved membranes and the resulting membrane deformation. The ERM protein ezrin is abundant and associated with cellular membranes that are flat, positively or negatively curved. Using in vitro and cell biology approaches, we assess mechanisms of ezrin's enrichment on curved membranes. We evidence that wild-type ezrin (ezrinWT) and its phosphomimetic mutant T567D (ezrinTD) do not deform membranes but self-assemble anti-parallelly, zipping adjacent membranes. EzrinTD's specific conformation reduces intermolecular interactions, allows binding to actin filaments, which reduces membrane tethering, and promotes ezrin binding to positively-curved membranes. While neither ezrinTD nor ezrinWT senses negative curvature alone, we demonstrate that interacting with curvature-sensing I-BAR-domain proteins facilitates ezrin enrichment in negatively-curved membrane protrusions. Overall, our work demonstrates that ezrin can tether membranes, or be targeted to curved membranes, depending on conformations and interactions with actin and curvature-sensing binding partners.

Effusion-based lymphoma with morphological regression but with clonal genetic features after aspiration.

Effusion-based lymphoma (EBL) is a rare but distinct entity of large B-cell lymphoma in effusion without association with human herpes virus-8 (HHV-8). Spontaneous regression after pleurocentesis has been observed; but to our knowledge, there are no reports on the morphological and molecular features of subsequent aspirations in regressing cases. Here, we report the case of a 92-year-old male with chronic obstructive pulmonary disease, who presented with right pleural effusion. He had no human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection, and CT scans revealed no mass lesion. The first pleural effusion aspiration cytology revealed large lymphoma cells with vesicular nuclei, irregular nuclear contours, and prominent nucleoli, consistent with EBL. The second aspiration cytology showed a few slightly enlarged lymphocytes in a background of small lymphocytes. Immunohistochemical study on cell block of the second aspiration revealed equal amounts of CD3-positive and CD20-positive cells. All these cells on the section tested negative for HHV-8 through immunohistochemistry and Epstein-Barr virus by in situ hybridization. Our initial impression was EBL in regression. However, flow cytometric immunophenotyping showed monotypic light chain expression of the gated B-cells. B-cell receptor gene rearrangement study showed a clonal result. Furthermore, fluorescence in situ hybridization revealed rearrangement of IGH gene. The diagnosis of the second aspiration was EBL with morphological regression but retained clonal genetic features. The patient passed away one month after diagnosis without chemotherapy. This case illustrated the importance of ancillary studies in confirming the clonal nature of a morphologically regressing EBL.

Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation.

Transendothelial cell macroaperture (TEM) tunnels control endothelium barrier function and are triggered by several toxins from pathogenic bacteria that provoke vascular leakage. Cellular dewetting theory predicted that a line tension of uncharacterized origin works at TEM boundaries to limit their widening. Here, by conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We develop a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. This establishes the critical role of ezrin and non-muscle myosin II (NMII) in the progressive implementation of line tension. Mechanistically, fluorescence-recovery-after-photobleaching experiments point for the upstream role of ezrin in stabilizing actin filaments at the edges of TEMs, thereby favouring their crosslinking by NMIIa. Collectively, our findings ascribe to ezrin and NMIIa a critical function of enhancing line tension at the cell boundary surrounding the TEMs by promoting the formation of an actomyosin ring.

DDR2 overexpression in urothelial carcinoma indicates an unfavorable prognosis: a large cohort study.

The migration ability of urothelial carcinoma corresponding to dismal prognosis had not been fully investigated. The interaction of extracellular collagen with a unique transmembrane receptor tyrosine kinase, Discoidin domain receptor 2 (DDR2), was selected by data mining. We arranged real-time reverse transcription polymerase chain reaction assays to evaluate the transcript levels in 26 urinary tract urothelial carcinoma and 26 urinary bladder urothelial carcinoma specimens, showing significantly increase corresponding to advanced primary stage (p = 0.003 and p < 0.001, respectively). An immunohistochemistry analysis and H-score calculation were performed to determine DDR2 expression in 340 urinary tract urothelial carcinoma and 295 urinary bladder urothelial carcinoma. Assessments of the correlation to clinicopathologic features, disease-specific survival, and metastasis-free survival were conducted. The transcript levels in advanced stage were higher than those in early stage and were correlated with poor prognosis. The higher expression was positively correlated to higher pT status (p < 0.001), higher histological grade (urinary tract, p = 0.041; urinary bladder, p < 0.001), greater vascular invasion (p < 0.001), and higher mitotic rate (urinary tract, p = 0.039; urinary bladder, p < 0.001). Higher expression also indicates significantly worse disease-specific survival and metastasis-free survival. In vitro study revealed knockdown of DDR2 resulted in a depletion of cellular viability, migratory, and invasive ability, supporting the oncogenic function of DDR2.

Efficiency Enhancement of Nanotextured Black Silicon Solar Cells Using Al2O3/TiO2 Dual-Layer Passivation Stack Prepared by Atomic Layer Deposition.

In this study, efficient nanotextured black silicon (NBSi) solar cells composed of silicon nanowire arrays and an Al2O3/TiO2 dual-layer passivation stack on the n(+) emitter were fabricated. The highly conformal Al2O3 and TiO2 surface passivation layers were deposited on the high-aspect-ratio surface of the NBSi wafers using atomic layer deposition. Instead of the single Al2O3 passivation layer with a negative oxide charge density, the Al2O3/TiO2 dual-layer passivation stack treated with forming gas annealing provides a high positive oxide charge density and a low interfacial state density, which are essential for the effective field-effect and chemical passivation of the n(+) emitter. In addition, the Al2O3/TiO2 dual-layer passivation stack suppresses the total reflectance over a broad range of wavelengths (400-1000 nm). Therefore, with the Al2O3/TiO2 dual-layer passivation stack, the short-circuit current density and efficiency of the NBSi solar cell were increased by 11% and 20%, respectively. In conclusion, a high efficiency of 18.5% was achieved with the NBSi solar cells by using the n(+)-emitter/p-base structure passivated with the Al2O3/TiO2 stack.

cDNA cloning and transcriptional expression profiles of a hexamerin in the oriental fruit fly, Bactrocera dorsalis.

A Bactrocera dorsalis hexamerin (BdAr) cDNA was cloned (GenBank accession no. KF815528), and its transcriptional expression profiles were determined. The complete 2,530-bp cDNA encodes a 780-amino acid protein with a predicted molecular mass of 94.01 kDa. The proportions of phenylalanine (7.8%), tyrosine (11.2%), and methionine (2.6%) in BdAr as well as all other amino acids are reported. BdAr transcripts were detected in the brain, flight muscle, foregut, Malpighian tubules, and fat body. In the larval stage, BdAr transcripts were expressed in the early third instar and increased in the late third instar. In pupae, the highest expression of BdAr mRNA was present on day 1, then declined and persisted through day 2 to day 8. In adult females, the relative expression of BdAr was significantly higher on day 0 and day 1 compared to day 6 to day 10 while it was highest in newly eclosed adult males. The comparison of the BdAr expression between 8-10-day-old males and females showed a higher level in females. Our phylogenetic analysis results suggest to us that BdAr is similar to Drosophila larval serum protein 1γ.