Epineurectomy of extracranial facial nerve trunk for non-flaccid sequelae following Bell's palsy: A single-arm trial.

BACKGROUND: Non-flaccid facial palsy sequelae manifest as sequelae following Bell's palsy. Currently, there are no effective remedies for addressing this issue. In this study, we proposed a new surgical solution, epineurectomy of the extracranial facial nerve trunk, and assessed its safety and efficacy as a potential remedy.. METHODS: In this single-arm trial, adult patients with non-flaccid facial palsy sequelae were enrolled and subjected to epineurectomy of the extracranial facial nerve trunk. The primary efficacy endpoint was the Sunnybrook scores at months 12 postoperatively. The secondary endpoints included non-flaccid facial palsy sequelae symptom scores, such as facial tightness or facial stiffness, facial synkinesis, eyefissures narrowing or difficulty in opening the eyes, House-Brackmann grade scale, and Facial Disability Index. RESULTS: A total of 22 patients were enrolled between July 2020 and January 2021. One patient was lost to follow up. One year after surgery, the Sunnybrook score was 72.0 (63.0 - 75.0) at 12 months versus 68.0 (58.0 - 70.8) at baseline. The mean difference was -5.4 (-7.2 to -3.6). The scores of facial tightness or facial stiffness, synkinesis, eye fissures narrowing or difficulty in opening eyes were 0.0 (0.0 - 1.0), 1.0 (1.0 - 1.0), 1.0 (1.0 - 2.0) at 12 months versus 3.0 (1.3 - 3.0), 2.0 (1.0 - 2.8), 2.0 (2.0 - 3.0) at baseline, respectively. The median (IQR) values of the Facial Disability Index physical function were 92.0 (90.0 - 95.0) at months 12, and the mean difference (95% CI) was -32 (-38 to -26) compared to baseline. The mean difference (95% CI) in the Facial Disability Index social/well-being function between month 12 and baseline was -38 (-46 to -31). CONCLUSIONS: Epineurectomy of the extracranial facial nerve trunk can effectively and safely alleviate the sequelae of non-flaccid facial palsy.

PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells.

PARP1 is crucial in DNA damage repair, chromatin remodeling, and transcriptional regulation. The principle of synthetic lethality has effectively guided the application of PARP inhibitors in treating tumors carrying BRCA1/2 mutations. Meanwhile, PARP inhibitors have exhibited efficacy in BRCA-proficient patients, further highlighting the necessity for a deeper understanding of PARP1 function and its inhibition in cancer therapy. Here, we unveil PIN2/TRF1-interacting telomerase inhibitor 1 (PINX1) as an uncharacterized PARP1-interacting protein that synergizes with PARP inhibitors upon its depletion across various cancer cell lines. Loss of PINX1 compromises DNA damage repair capacity upon etoposide treatment. The vulnerability of PINX1-deficient cells to etoposide and PARP inhibitors could be effectively restored by introducing either a full-length or a mutant form of PINX1 lacking telomerase inhibitory activity. Mechanistically, PINX1 is recruited to DNA lesions through binding to the ZnF3-BRCT domain of PARP1, facilitating the downstream recruitment of the DNA repair factor XRCC1. In the absence of DNA damage, PINX1 constitutively binds to PARP1, promoting PARP1-chromatin association and transcription of specific DNA damage repair proteins, including XRCC1, and transcriptional regulators, including GLIS3. Collectively, our findings identify PINX1 as a multifaceted partner of PARP1, crucial for safeguarding cells against genotoxic stress and emerging as a potential candidate for targeted tumor therapy.

The Effect of Expanded Vermiculite on the Fire Resistance of Waterborne Acrylic Coatings.

Due to their ability to prevent or slow the spread of fires, fire-retardant coatings are utilized as the main means of fire protection for steel structures, combining easy application and high economic efficiency. This study investigates the effects of the particle size and dosage of expanded vermiculite (EV) on the fire resistance and application performance of coatings. Ammonium polyphosphate, melamine, and pentaerythritol were used as intumescent fire-retardant systems, along with waterborne hydroxyl-modified acrylic resins as the film-forming substances. The properties of fire resistance coatings were tested via scanning electron microscope (SEM), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), limiting oxygen index (LOI), and cone calorimetry. The excellent fire performance of the coatings with 3 wt.% 300-mesh EV was proven, exhibiting a relative expansion of 30.43 times. Moreover, the surface structure of the charcoal layer was dense. The total smoke production (TSP) and smoke concentration (TSR) were only 0.18 m2 and 0.25 m2/m2.

The Relationship between Football Participation and Sport Trait Confidence for Adolescents: A Chain-Mediated Effect of Collective Self-Esteem and Self-Esteem.

To investigate the relationship between sports participation and sport trait confidence, 1659 teenagers in primary and secondary schools who regularly play football were asked to complete the Sports Participation Scale, Collective Self-Esteem Scale, Self-Esteem Scale, and Sport Trait Confidence Scale. The results show that (1) the positive prediction of football participation on sport trait confidence is not significant; (2) collective self-esteem and self-esteem play a mediating role between football participation and sport trait confidence; (3) the mediating effect occurs through three pathways. The study provides theoretical guidance and empirical evidence for the lead and intervention of adolescent football participation on sport trait confidence. This study created a chain-mediated model to examine the mediating role of collective self-esteem and self-esteem in their relationship, as well as the impact of the two as chain mediators on football participation and sport trait confidence.

Management of Meige syndrome with bilateral trigeminal and facial nerves combing.

Objective: Meige syndrome (MS) is an adult-onset segmental dystonia for which no satisfactory remedy currently exists. Our team developed a novel surgical approach called bilateral trigeminal/facial nerve combing (BTFC). This study aimed to evaluate the outcomes of patients who underwent BFTC (Clinical Trial Registry Number: ChiCTR2000033481). Method: We assigned 22 patients with MS to undergo BTFC. The primary outcome was assessed using the movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-M) at 12 months postoperatively. The second outcome was evaluated using the Medical Outcome Study (MOS) 36-item Short Form Health Survey (SF-36), the dysfunction subscale of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-D), and the sub-item scores of the BFMDRS-M. Safety outcomes included the House-Brackmann (HB) functional grading score and the visual analog scale (VAS) for facial numbness. Results: At the final follow-up at 12 months, the BFMDRS-M showed a mean improvement of 70.7% from baseline. Mean scores of the BFMDRS-M sub-motor (including the eyes, mouth, and speech/swallowing) improved by 65.6, 81.00, and 60%, respectively. The median score of the total BFMDRS-D score was 0.70 ± 1.17 compared with 1.86 ± 2.21 at baseline. There were no serious operative complications in this population. The quality of life of the patients significantly improved (P < 0.05). Conclusion: BFTC has proven to be effective in relieving the symptoms of Meige syndrome. This novel surgical approach offers a new alternative treatment for patients who have failed to respond to medications, botulinum toxin injections, and deep brain stimulation (DBS). Clinical Trial Registration: https://www.chictr.org.cn/bin/project/edit?pid=54567, ChiCTR2000033481.

Salvaging the transected hypoglossal nerve using descendens hypoglossi in patients undergoing hypoglossal-facial nerve anastomosis for facial palsy: a randomized clinical trial.

OBJECTIVE: Hypoglossal-facial nerve anastomosis (HFA) is the most commonly used surgical treatment for severe facial palsy that does not respond to conservative treatments. A major complication of HFA is the loss of tongue function. The authors aimed to evaluate whether anastomosing the transected hypoglossal nerve using the ramus descendens hypoglossi could prevent tongue deviation and dysfunction in patients undergoing HFA. METHODS: In this randomized trial, adult patients with severe peripheral facial palsy (House-Brackmann grade V or VI) who did not respond to at least 6 months of conservative treatment were randomized at a 1:1 ratio to undergo either HFA alone (control group) or HFA plus anastomosis between the hypoglossal nerve and descendens hypoglossi (intervention group). The primary endpoint was tongue deviation angle at 12 months. Key secondary endpoints included tongue disability (chewing difficulty, swallowing defect, and articulation defect), tongue disability index (TDI; range 1-4, with a higher score indicating more severe disability), and facial nerve function. RESULTS: Twenty patients were enrolled (10 in each group). At 12 months, the tongue deviation angle was significantly lower in the intervention group than in the control group (7.8° ± 5.1° vs 23.6° ± 9.6°, p < 0.001). Although not statistically significant, the intervention group had lower rates of chewing difficulty (1/10 vs 3/10, p = 0.58), swallowing defect (1/10 vs 5/10, p = 0.14), and articulation defect (2/10 vs 6/10, p = 0.17). TDI was significantly lower in the intervention group (1.5 ± 0.6 vs 2.5 ± 0.3, p < 0.001). The percentage of the patients achieving House-Brackmann grade II or III was 80% in each group. CONCLUSIONS: Anastomosis of the descendens hypoglossi to the transected hypoglossal nerve attenuated tongue deviation in patients undergoing HFA for facial palsy, without compromising facial nerve function. Clinical trial registration no: ChiCTR2000034372 (Chinese Clinical Trials Registry).

Discrimination and evaluation of commercial salmons by low-molecule-weight compounds: Oligopeptides and phosphatides.

In this study, the overall sensory characteristics and low-molecule-weight compounds were analyzed to achieve the discrimination of different commercial salmons and investigate the salmon's sensory and nutritional quality. The results showed that above the overall sensory properties, O. mykiss, S. salar, and O. kisutch were the most satisfied salmons by the panel with the desirable texture and flavor, which displayed a large potential for growth in the consumption market. The alcohols and sulfur compounds were key volatile compounds contributing to typical aroma of O. masou and O. gorbuscha, response higher than others by 147% to 167%. The oligopeptides and phospholipids in salmon could be used as biomarkers for discrimination of these salmon. Oligopeptides were also closely related to the taste quality of salmon. Seventeen oligopeptides showed potential umami activity based on molecular docking results, especially Arg-Val and Ser-Asn, which were the key tastants contributing to the umami of salmon.

NAMPT-targeting PROTAC and nicotinic acid co-administration elicit safe and robust anti-tumor efficacy in NAPRT-deficient pan-cancers.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the biosynthesis of nicotinamide adenine dinucleotide (NAD+), making it a potential target for cancer therapy. Two challenges hinder its translation in the clinic: targeting the extracellular form of NAMPT (eNAMPT) remains insufficient, and side effects are observed in normal tissues. We previously utilized proteolysis-targeting chimera (PROTAC) to develop two compounds capable of simultaneously degrading iNAMPT and eNAMPT. Unfortunately, the pharmacokinetic properties were inadequate, and toxicities similar to those associated with traditional inhibitors arose. We have developed a next-generation PROTAC molecule 632005 to address these challenges, demonstrating exceptional target selectivity and bioavailability, improved in vivo exposure, extended half-life, and reduced clearance rate. When combined with nicotinic acid, 632005 exhibits safety and robust efficacy in treating NAPRT-deficient pan-cancers, including xenograft models with hematologic malignancy and prostate cancer and patient-derived xenograft (PDX) models with liver cancer. Our findings provide clinical references for patient selection and treatment strategies involving NAMPT-targeting PROTACs.

Microvascular Decompression Using the Gelatin Sponge Insertion Technique for Trigeminal Neuralgia: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Microvascular decompression (MVD) is the primary surgical intervention for trigeminal neuralgia (TN), with Teflon being the most conventional decompressing material. However, Teflon has been associated with adhesion and granulomas after MVD, which closely correlated with the recurrence of TN. Therefore, we developed a new technique to prevent direct contact between Teflon and nerve. The purpose of this study is to compare the efficacy of MVD using the gelatin sponge (GS) insertion technique with that of Teflon inserted alone in treating primary TN. METHODS: We retrospectively analyzed the medical records and the follow-up data of 734 patients with unilateral primary TN who underwent MVD at our center from January 2014 to December 2019. After exclusions, we identified 313 cases of GS-inserted MVD and 347 cases of traditional MVD. The follow-up exceeded 3 years. RESULTS: The operating time of the GS-inserted group was longer than that of the Teflon group (109.38 ± 14.77 vs 103.53 ± 16.02 minutes, P < .001). There was no difference between 2 groups in immediate surgical outcomes and postoperative complications. The yearly recurrence rate for GS-inserted MVD was lower at first (1.0%), second (1.2%), and third (1.2%) years after surgery, compared with its counterpart of Teflon group (3.7%, 2.9%, and 1.7% respectively). The first-year recurrence rate (P = .031) and total recurrence rate in 3 years (P = .013) was significantly lower in the GS-inserted group than Teflon group. Kaplan-Meier survival analysis demonstrated better outcomes in GS-inserted MVD groups (P = .020). CONCLUSION: The application of the GS insertion technique in MVD reduced first-year postoperative recurrence of TN, with similar complications rates compared with traditional MVD.

Surgical Removal of Foramen Ovale Osteophyte Completely Relieved Atypical Trigeminal Neuralgia: A Case Report and Literature Review.

Atypical trigeminal neuralgia (TN), usually caused by nonvascular compression, lacks a clearly localized trigger and complete remission periods. Although variations of foramen ovale may compress the mandibular nerve branch of the trigeminal nerve, resulting in atypical TN, only a few case reports are reported in the literature. The authors describe a case of a 50-year-old female diagnosed with atypical TN for two months. A high-resolution computed tomography imaging revealed an osteophyte of the left foramen ovale that may compress the mandibular nerve branch of the trigeminal nerve. The patient underwent osteophyte resection, and the pain disappeared completely and immediately after surgery without recurrence in the follow-up to six months. The numbness was also relieved slightly. This case provides a new perspective on the clinical diagnosis and treatment of patients with atypical TN.

Transient hydroxycholesterol treatment restrains TCR signaling to promote long-term immunity.

T cell receptor (TCR) plays a fundamental role in adaptive immunity, and TCR-T cell therapy holds great promise for treating solid tumors and other diseases. However, there is a noticeable absence of chemical tools tuning TCR activity. In our study, we screened natural sterols for their regulatory effects on T cell function and identified 7-alpha-hydroxycholesterol (7a-HC) as a potent inhibitor of TCR signaling. Mechanistically, 7a-HC promoted membrane binding of CD3ε cytoplasmic domain, a crucial signaling component of the TCR-CD3 complex, through alterations in membrane physicochemical properties. Enhanced CD3ε membrane binding impeded the condensation between CD3ε and the key kinase Lck, thereby inhibiting Lck-mediated TCR phosphorylation. Transient treatments of TCR-T cells with 7a-HC resulted in reduced signaling strength, increased memory cell populations, and superior long-term antitumor functions. This study unveils a chemical regulation of TCR signaling, which can be exploited to enhance the long-term efficacy of TCR-T cell therapy.

The role of lncFABP4 in modulating adipogenic differentiation in buffalo intramuscular preadipocytes.

Intramuscular fat (IMF) is a crucial determinant of meat quality and is influenced by various regulatory factors. Despite the growing recognition of the important role of long noncoding RNAs (lncRNAs) in IMF deposition, the mechanisms underlying buffalo IMF deposition remain poorly understood. In this study, we identified and characterized a lncRNA, lncFABP4, which is transcribed from the antisense strand of fatty acid-binding protein 4 (FABP4). lncFABP4 inhibited cell proliferation in buffalo intramuscular preadipocytes. Moreover, lncFABP4 significantly increased intramuscular preadipocyte differentiation, as indicated by an increase in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARG), CCAAT enhancer binding protein alpha (C/EBPα), and FABP4. Mechanistically, lncFABP4 was found to have the potential to regulate downstream gene expression by participating in protein-protein interaction pathways. These findings contribute to further understanding of the intricate mechanisms through which lncRNAs modulate intramuscular adipogenesis in buffaloes.

From suppressor to enhancer: IL-10's alternative role in CAR-T cell therapies against solid tumors.

Aiming to improve the effector function of CAR-T cells, Zhao et al.1 report that IL-10 metabolically reprograms CAR-T cells, and this promotes their effectiveness against solid tumors and challenges IL-10's perceived role as merely immunosuppressive. This simple but promising strategy fosters durable immune memory and eagerly awaits validation in clinical trials.

Nitrogen-Doped CoP with optimized d-Band center as bidirectional electrocatalyst for high areal capacity of Li-S battery.

Lithium polysulfide (LiPSs) shuttle effect and difficulties with Li2S oxidation are hinder the marketization of lithium-sulfur batteries. We suggest using a bidirectional catalyst in the sulfur host to solve these problems. We produced a nitrogen-doped cobalt phosphide (N-CoP@NC) as a sulfur carrier in this work. The introduction of nitrogen into cobalt phosphide enhances the electron transmission speed and forms shorter Co-N bonds. As a result, new defect energy levels are introduced, leading to an increase in the charge number of Co central atoms, which abate the Li-S and SS bonds in Li2S and Li2S4, thereby promoting the oxidation of Li2S during charging, as well as the alteration process of LiPSs during charge and discharge. Additionally, the crystal flaws that result in increased Co-S bond formation help to boost polysulfides' adsorption ability. The Li-S batteries shows outstanding cyclability when paired with this electrocatalyst, demonstrating a minimal capacity degradation rate of only 0.07 % per cycle over 500 cycles at a rate of 0.5C. As a result, incorporating anion doping in the host emerges as a promising method for crafting materials tailored for Li-S batteries.

Hypoxic Bone Mesenchymal Stem Cell-Derived Exosomes Direct Schwann Cells Proliferation, Migration, and Paracrine to Accelerate Facial Nerve Regeneration via circRNA_Nkd2/miR-214-3p/MED19 Axis.

Background: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism. Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments. Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p. Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI.

Evaluation of generic EMG-Torque models across two Upper-Limb joints.

Advanced single-use dynamic EMG-torque models require burdensome subject-specific calibration contractions and have historically been assumed to produce lower error than generic models (i.e., models that are identical across subjects and muscles). To investigate this assumption, we studied generic one degree of freedom (DoF) models derived from the ensemble median of subject-specific models, evaluated across subject, DoF and joint. We used elbow (N = 64) and hand-wrist (N = 9) datasets. Subject-specific elbow models performed statistically better [5.79 ± 1.89 %MVT (maximum voluntary torque) error] than generic elbow models (6.21 ± 1.85 %MVT error). However, there were no statistical differences between subject-specific vs. generic models within each hand-wrist DoF. Next, we evaluated generic models across joints. The best hand-wrist generic model had errors of 6.29 ± 1.85 %MVT when applied to the elbow. The elbow generic model had errors of 7.04 ± 2.29 %MVT when applied to the hand-wrist. The generic elbow model was statistically better in both joints, compared to the generic hand-wrist model. Finally, we tested Butterworth filter models (a simpler generic model), finding no statistical differences between optimum Butterworth and subject-specific models. Overall, generic models simplified EMG-torque training without substantive performance degradation and provided the possibility of transfer learning between joints.