Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Immunodeviation towards T cell-mediated immune response in the testes of LPS-induced mouse epididymo-orchitis.

The testicular consequences of acute epididymo-orchitis remain largely unelucidated in long-term damage, which might be a neglected factor for male infertility. In this study, the differential phenotype of testicular immune cell subpopulations in lipopolysaccharide (LPS)-induced mouse epididymo-orchitis were analyzed by flow cytometry on day 1, day 7, and day 28. The number of macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) steadily decreased in the testes with inoculation. Total F4/80-CD11c+ dendritic cells (DCs) maintained a relatively stable level, whereas conventional type 1 dendritic cells (cDC1) increased gradually from day 1 to day 28. There was a lower number of CD4+ and CD8+ T cells at day 1 and day 7, and they had similar results with a ceiling level at day 28. The testes displayed a higher level of CD3+ T cells but a lower frequency of macrophages, cDC2, and neutrophils at 28 days post-inoculation compared with the epididymis. In summary, our data indicates acute epididymo-orchitis could lead to long-term damage in the testes, which is characterized by CD3+ T cell (including CD4+ and CD8+ T cells)-mediated immune responses.

Styxl2 regulates de novo sarcomere assembly by binding to non-muscle myosin IIs and promoting their degradation.

Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown in zebrafish or genetic knockout in mice, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one with Styxl2 being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role in de novo sarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions in de novo sarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotes de novo sarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.

A novel MAPT variant (E342K) as a cause of familial progressive supranuclear palsy.

Background: MAPT variants are a known cause of frontotemporal dementia and Parkinsonian syndrome, of which progressive supranuclear palsy syndrome (PSP) is a rare manifestation. Objective: To report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants. Methods: A comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient's pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms. Results: The proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier. Conclusion: The PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT.

Attention decoupled contrastive learning for semi-supervised segmentation method based on data augmentation.

OBJECTIVE: Deep learning algorithms have demonstrated impressive performance by leveraging large labeled data. However, acquiring pixel-level annotations for medical image analysis, especially in segmentation tasks, is both costly and time-consuming, posing challenges for supervised learning techniques. Existing semi-supervised methods tend to underutilize representations of unlabeled data and handle labeled and unlabeled data separately, neglecting their interdependencies. APPROACH: To address this issue, we introduce the Data-Augmented Attention-Decoupled Contrastive model (DADC). This model incorporates an attention decoupling module and utilizes contrastive learning to effectively distinguish foreground and background, significantly improving segmentation accuracy. Our approach integrates an augmentation technique that merges information from both labeled and unlabeled data, notably boosting network performance, especially in scenarios with limited labeled data. MAIN RESULTS: We conducted comprehensive experiments on the ABUS dataset and the results demonstrate that DADC outperforms existing segmentation methods in terms of segmentation performance.

CPT2 mediated fatty acid oxidation is dispensable for humoral immunity.

B cell activation is accompanied by dynamic metabolic reprogramming, supported by a multitude of nutrients that include glucose, amino acids and fatty acids. While several studies have indicated that fatty acid mitochondrial oxidation is critical for immune cell functions, contradictory findings have been reported. Carnitine palmitoyltransferase II (CPT2) is a critical enzyme for long-chain fatty acid oxidation in mitochondria. Here, we test the requirement of CPT2 for humoral immunity using a mouse model with a lymphocyte specific deletion of CPT2. Stable 13C isotope tracing reveals highly reduced fatty acid-derived citrate production in CPT2 deficient B cells. Yet, CPT2 deficiency has no significant impact on B cell development, B cell activation, germinal center formation, and antibody production upon either thymus-dependent or -independent antigen challenges. Together, our findings indicate that CPT2 mediated fatty acid oxidation is dispensable for humoral immunity, highlighting the metabolic flexibility of lymphocytes.

Automatic breast ultrasound (ABUS) tumor segmentation based on global and local feature fusion.

Accurate segmentation of tumor regions in automated breast ultrasound (ABUS) images is of paramount importance in computer-aided diagnosis system. However, the inherent diversity of tumors and the imaging interference pose great challenges to ABUS tumor segmentation. In this paper, we propose a global and local feature interaction model combined with graph fusion (GLGM), for 3D ABUS tumor segmentation. In GLGM, we construct a dual branch encoder-decoder, where both local and global features can be extracted. Besides, a global and local feature fusion module is designed, which employs the deepest semantic interaction to facilitate information exchange between local and global features. Additionally, to improve the segmentation performance for small tumors, a graph convolution-based shallow feature fusion module is designed. It exploits the shallow feature to enhance the feature expression of small tumors in both local and global domains. The proposed method is evaluated on a private ABUS dataset and a public ABUS dataset. For the private ABUS dataset, the small tumors (volume smaller than 1 cm3) account for over 50% of the entire dataset. Experimental results show that the proposed GLGM model outperforms several state-of-the-art segmentation models in 3D ABUS tumor segmentation, particularly in segmenting small tumors.

Microscopic Electric Rotary Grinding of Plaques Combined with Graft Repair in the Management of Peyronie's Disease.

Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.

The Clinical Investigation on Varicocele and Sperm Quality in the Tibet an Plateau of China: A Prospectively Planned Retrospective Cohort Study.

Varicoceles are a common cause of male infertility, affecting up to 35% of men undergoing fertility evaluations. This study aims to investigate the potential influence of altitude and residence time on the occurrence of varicoceles, as well as on sperm quality and sterility in plateau areas. A total of 168 patients with varicocele were enrolled in the study, and the study population was divided into groups based on their direct exposure to different high altitudes due to their living locations. The internal diameter in Quiet breath (Dr), internal diameter in Valsalva maneuver (Dv), reflux peak value, and reflux time are gradually increased accompanied with altitude elevation and residence time extension. The number of cases above 4,500 m also increased with the severity of varicocele, and the altitude of clinical types was higher than that of subclinical types of varicocele. Especially above 4,500 m, the Dv, Dr, reflux peak value, and reflux time all increased with the severity of varicocele. The severity of varicocele was positively correlated with the residence time in plateau area. Patients with residence time of more than 1 year had higher values of Dr, Dv, differentiation time, reflux peak value, and reflux time than those with residence time of less than 1 year. Compared to 3,650 m, patients with varicocele in 4,500 m also have worse semen quality. Both altitude and residence time are strongly positively related to the severity and incidence rate of varicocele in plateau areas.

The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.

Rag-GTPase-TFEB/TFE3 axis controls B cell mitochondrial fitness and humoral immunity independent of mTORC1.

During the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and generate plasmablasts in both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer's patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish Rag-GTPase-TFEB/TFE3 axis as an mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.

Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.

BACKGROUND: Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. OBJECTIVE: To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. RESULTS AND LIMITATIONS: The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. CONCLUSIONS: Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. PATIENT SUMMARY: In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

The nutrient-sensing Rag-GTPase complex in B cells controls humoral immunity via TFEB/TFE3-dependent mitochondrial fitness.

During the humoral immune response, B cells undergo rapid metabolic reprogramming with a high demand for nutrients, which are vital to sustain the formation of the germinal centers (GCs). Rag-GTPases sense amino acid availability to modulate the mechanistic target of rapamycin complex 1 (mTORC1) pathway and suppress transcription factor EB (TFEB) and transcription factor enhancer 3 (TFE3), members of the microphthalmia (MiT/TFE) family of HLH-leucine zipper transcription factors. However, how Rag-GTPases coordinate amino acid sensing, mTORC1 activation, and TFEB/TFE3 activity in humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and generate plasmablasts in both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer's patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish Rag-GTPase-TFEB/TFE3 pathway as an mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.

Analyzing prehospital delays in recurrent acute ischemic stroke: Insights from interpretable machine learning.

OBJECTIVE: This study investigates prehospital delays in recurrent Acute Ischemic Stroke (AIS) patients, aiming to identify key factors contributing to these delays to inform effective interventions. METHODS: A retrospective cohort analysis of 1419 AIS patients in Shenzhen from December 2021 to August 2023 was performed. The study applied the Extreme Gradient Boosting (XGBoost) algorithm and SHapley Additive exPlanations (SHAP) for identifying determinants of delay. RESULTS: Living with others and lack of stroke knowledge emerged as significant risk factors for delayed hospital presentation in recurrent AIS patients. Key features impacting delay times included residential status, awareness of stroke symptoms, presence of conscious disturbance, diabetes mellitus awareness, physical weakness, mode of hospital presentation, type of stroke, and presence of coronary artery disease. CONCLUSION: Prehospital delays are similarly prevalent among both recurrent and first-time AIS patients, highlighting a pronounced knowledge gap in the former group. This discovery underscores the urgent need for enhanced stroke education and management. PRACTICE IMPLICATION: The similarity in prehospital delay patterns between recurrent and first-time AIS patients emphasizes the necessity for public health initiatives and tailored educational programs. These strategies aim to improve stroke response times and outcomes for all patients.

Curculigoside, a traditional Chinese medicine monomer, ameliorates oxidative stress in Alzheimer's disease mouse model via suppressing ferroptosis.

Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co-expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis-related specific markers in OA and scopolamine-induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD-promoting factors (such as Aß1-42, p-tau) and ferroptosis-promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up-regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis.

Sanchi-mediated inactivation of IL1B accelerates wound healing through the NFκB pathway deficit.

Context: Sanchi promotes wound healing by repressing fibroblast proliferation. Objective: This study examined the effect of Sanchi on keratinocytes (KCs) and microvascular endothelial cells (MECs) and rats with skin injury. Materials & methods: Hydrogels containing different concentrations of Sanchi extract were prepared to observe wound closure over 10 days. SD rats were divided into the control, Hydrogel, 5% Hydrogel, 10% Hydrogel, 10% Hydrogel + Ad5-NC, and 10% Hydrogel + Ad5-IL1B groups. KCs and MECs were induced with H2O2 for 24 h. Cell viability, apoptosis, and the levels of inflammation- and oxidative stress-related factors were examined. The effect of IL1B on wound healing was also evaluated. Results: Compared to the Control group (83% ± 7.4%) or Hydrogel without Sanchi extract (84% ± 8.5%), Hydrogel with 5% (95% closure ± 4.0%) or 10% Sanchi extract (98% ± 1.7%) accelerated wound healing in rats and attenuated inflammation and oxidative stress. Hydrogels containing Sanchi extract increased collagen deposition and CD31 expression in tissues. H2O2 (100 µM) induced injury in KCs and MECs, whereas Sanchi rescued the viability of KCs and MECs. Sanchi inhibited cell inflammation and oxidative stress and decreased apoptosis. As Sanchi blocked the NFκB pathway via IL1B, IL1B mitigated the therapeutic effect of Sanchi. Discussion and conclusion: Sanchi demonstrated therapeutic effects on wound healing in rats by promoting KCs and MECs activity. These findings provide valuable information for the clinical application of Sanchi, which needs to be validated in future clinical trials.

Research on accurate pipetting complementation model for high-throughput molecular detection platform.

The incidence of infectious diseases has risen in recent years, leading to a significant surge in the demand for medical molecular detection. High-throughput molecular detection platforms play a crucial role in facilitating rapid and efficient molecular detection. Among the various techniques employed in high-throughput molecular detection, microliquid transfer stands out as one of the most frequently utilized methods. However, ensuring the accuracy of liquid transfer poses a challenge due to variations in the physical and chemical properties of different samples and reagents. In this study, a pipetting complementation model was developed specifically for the serum, paraffin oil, and throat swabs. The aim was to enhance the transfer accuracy of diverse liquids in the context of high-throughput molecular detection, ultimately ensuring detection reliability and stability. The experimental findings revealed notable improvements in pipetting accuracy after compensating for the three liquids. In particular, the pipetting error rates decreased by 52.5, 96, and 71.4% for serum, paraffin oil, and throat swabs, respectively. These results underscore the model's effectiveness in providing reliable support for the precise transfer of liquids on the high-throughput molecular detection platform.

A prospective cohort study on perioperative percutaneous balloon compression for trigeminal neuralgia: safety and efficacy analysis.

With the recent emergence of percutaneous balloon compression (PBC) as a promising treatment for trigeminal neuralgia (TN), there is a growing need for research on its safety and efficacy. This study was designed to evaluate the safety and efficacy of PBC in the treatment of TN patients during the perioperative period. This study involved a total of 400 TN patients who were selected and treated with PBC at our institution. The clinical data and short-term outcomes were analyzed based on sex, initial PBC treatment for TN, and subsequent PBC treatment for recurrent TN after previous PBC or microvascular decompression (MVD) or radiofrequency thermocoagulation (RFT). No statistically significant difference was found when comparing postoperative pain relief between male and female patients with TN. Nevertheless, female patients were found to be more vulnerable than male patients to abnormal facial sensations (P = 0.001), diplopia (P = 0.015), postoperative headache (P = 0.012), and hyposmia (P = 0.029). Additionally, it was observed that there was no substantial difference in the postoperative pain relief rate between the first-time PBC group and PBC for recurrent TN patients postoperatively following procedures such as PBC, MVD, and RFT. In conclusion, this study has shown that PBC treatment is effective in managing TN in both males and females, regardless of whether the treatment was administered as a primary intervention or following prior surgical procedures such as PBC, MVD, or RFT. Nonetheless, it is noted that the risk of postoperative complications appears to be higher in female patients compared to male patients.

PP2A catalytic subunit alpha is critically required for CD8+ T cell homeostasis and anti-bacterial responses.

While the functions of tyrosine phosphatases in T cell biology have been extensively studied, our knowledge on the contribution of serine/threonine phosphatases in T cells remains poor. Protein phosphatase 2A (PP2A) is one of the most abundantly expressed serine/threonine phosphatases. It is important in thymocyte development and CD4+ T cell differentiation. Utilizing a genetic model in which its catalytic subunit alpha isoform (PP2A Cα) is deleted in T cells, we investigated its contribution to CD8+ T cell homeostasis and effector functions. Our results demonstrate that T cell intrinsic PP2A Cα is critically required for CD8+ T cell homeostasis in secondary lymphoid organs and intestinal mucosal site. Importantly, PP2A Cα deficient CD8+ T cells exhibit reduced proliferation and survival. CD8+ T cell anti-bacterial response is strictly dependent on PP2A Cα. Expression of Bcl2 transgene rescues CD8+ T cell homeostasis in spleens, but not in intestinal mucosal site, nor does it restore the defective anti-bacterial responses. Finally, proteomics and phosphoproteomics analyses reveal potential targets dependent on PP2A Cα, including mTORC1 and AKT. Thus, PP2A Cα is a key modulator of CD8+ T cell homeostasis and effector functions.