Long-Term Follow-Up of Patients Undergoing Thalidomide Therapy for Transfusion-Dependent ß-Thalassaemia: A Single-Center Experience.

Objective: We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent ß-thalassemia (TDT). Methods: Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed. Results: At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (P<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed. Conclusion: Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.

3D Gaussian Splatting as New Era: A Survey.

3D Gaussian Splatting (3D-GS) has emerged as a significant advancement in the field of Computer Graphics, offering explicit scene representation and novel view synthesis without the reliance on neural networks, such as Neural Radiance Fields (NeRF). This technique has found diverse applications in areas such as robotics, urban mapping, autonomous navigation, and virtual reality/augmented reality, just name a few. Given the growing popularity and expanding research in 3D Gaussian Splatting, this paper presents a comprehensive survey of relevant papers from the past year. We organize the survey into taxonomies based on characteristics and applications, providing an introduction to the theoretical underpinnings of 3D Gaussian Splatting. Our goal through this survey is to acquaint new researchers with 3D Gaussian Splatting, serve as a valuable reference for seminal works in the field, and inspire future research directions, as discussed in our concluding section.

Quasi-distributed quartz enhanced photoacoustic spectroscopy sensing based on hollow waveguide micropores.

In this Letter, a quasi-distributed quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensing system based on hollow waveguide micropores (HWGMP) was reported for the first time, to the best of our knowledge. Three micropores were developed on the HWG to achieve distributed detection units. Three self-designed quartz tuning forks (QTFs) with low resonant frequency of 8.7 kHz were selected as the acoustic wave transducer to improve the detection performance. Compared with micro-nano fiber evanescent wave (FEW) QEPAS, the HWGMP-QEPAS sensor has advantages such as strong anti-interference ability, low loss, and low cost. Acetylene (C2H2) was selected as the target gas to verify the characteristics of the reported sensor. The experimental results showed that the three QTFs almost had the same sensing ability and possessed an excellent linear concentration response to C2H2. The minimum detection limits (MDLs) for the three QTFs were determined as 68.90, 68.31, and 66.62 ppm, respectively. Allan deviation analysis indicated that the system had good long-term stability, and the MDL can be improved below 3 ppm in an average time of 1000 s.

Mortality of Patients With Sepsis Administered Piperacillin-Tazobactam vs Cefepime.

Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. Design, Setting, and Participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. Main Outcomes and Measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Conclusions and Relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Ultra-highly sensitive dual gases detection based on photoacoustic spectroscopy by exploiting a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser.

Photoacoustic spectroscopy (PAS) as a highly sensitive and selective trace gas detection technique has extremely broad application in many fields. However, the laser sources currently used in PAS limit the sensing performance. Compared to diode laser and quantum cascade laser, the solid-state laser has the merits of high optical power, excellent beam quality, and wide tuning range. Here we present a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser used as light source in a PAS sensor for trace gas detection. The self-built solid-state laser had an emission wavelength of ~2 µm with Tm:YAP crystal as the gain material, with an excellent wavelength and optical power stability as well as a high beam quality. The wide wavelength tuning range of 9.44 nm covers the absorption spectra of water and ammonia, with a maximum optical power of ~130 mW, allowing dual gas detection with a single laser source. The solid-state laser was used as light source in three different photoacoustic detection techniques: standard PAS with microphone, and external- and intra-cavity quartz-enhanced photoacoustic spectroscopy (QEPAS), proving that solid-state laser is an attractive excitation source in photoacoustic spectroscopy.

Design and Optimization of Self-Supporting Surfaces with Arch Beams.

The paper presents a new method for constructing self-supporting surfaces using arch beams that are designed to convert their thrust into supporting force, thereby eliminating shear stress and bending moments. Our method allows for the placement of the arch beams on the boundary or within a surface and partitions the surface into multiple self-supporting parts. The use of arch beams enhances stability and durability, adds aesthetic appeal, and allows for greater flexibility in the design process. We develop an iterative algorithm for designing selfsupporting surfaces with arch beams that enables the user to control the shape of the beams and surface through intuitive parameters and specify the desired location of the arch beams. We verify the physical stability of the structure using finite element analysis. Experimental results show that our method can produce visually pleasing self-supporting surfaces that satisfy the equilibrium equation with high accuracy.

Causal associations between autoimmune diseases and sarcopenia-related traits: a bi-directional Mendelian randomization study.

Background: Sarcopenia is common in patients with autoimmune diseases (ADs); however, the causal associations between ADs and sarcopenia remain unclear. Therefore, this study investigated the causal associations using bi-directional Mendelian randomization analysis. Methods: Exposure-related single-nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWASs). GWAS statistics for common ADs [Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PSO), and multiple sclerosis (MS)] and sarcopenia-related traits [hand grip strength (HGS), appendicular fat-free mass (FFM), and walking pace] were obtained from public datasets. Inverse-variance weighting as the main method was used to evaluate the causal effect. Results: Genetically predicted CD had causal effects on whole-body FFM (ß = -0.005, p = 0.001), leg FFM (ßleft = -0.006, p = 1.8E-4; ßright = -0.007, p = 2.0E-4), and arm FFM (ßleft = -0.005, p = 0.005; ßright = -0.005, p = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (ßleft = -2.06, p = 2.8E-38; ßright = -2.311, p = 2E-20), whole-body FFM (ß = -0.842, p = 4.7E-10), leg FFM (ßleft = -0.666, p = 2.6E-6; ßright = -0.073, p = 2.1E-3), arm FFM (ßleft = -0.63, p = 4.4E-6; ßright = -0.736, p = 4.4E-8), and walking pace (ß = -1.019, p = 6.2E-14). In the reverse direction, HGS (odds ratio [OR]left = 10.257, p = 3.6E-5; ORright = 16.445, p = 3.7E-7) had causal effects on CD, while HGS (ORleft = 0.994, p = 0.004; ORright = 0.993, p = 1.4E-4), leg FFM (ORleft = 1.003, p = 0.005; ORright = 1.005, p = 1.9E-4), and walking pace (OR = 0.985, p = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits. Conclusion: Our study demonstrated that the genetic susceptibility to CD and RA was associated with high risk of sarcopenia, and some sarcopenia-related traits had causal effects on CD or RA.

Circ_0001786 facilitates gefitinib resistance and malignant progression in non-small cell lung cancer via miR-34b-5p/SRSF1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a widespread cancer and gefitinib is a primary therapy for NSCLC patients. Nevertheless, the underlying mechanisms for the progression of acquired drug resistance have not been clarified. The aim of this study was to investigate the role of circular RNA (circ_0001786) in gefitinib-resistant NSCLC. METHODS: Firstly, the expression of circ_0001786, miR-34b-5p and SRSF1 were assayed using qRT-PCR. Subsequently, CCK-8 test was utilized to measure the semi-inhibitory concentration (IC50) of cellular gefitinib. Apoptosis was identified by flow cytometry. At last, dual luciferase assay was applied to prove the binding association between miR-34b-5p, circ_0001786 or SRSF1. RESULTS: Our research disclosed that circ_0001786 was heightened in gefitinib-resistant NSCLC cells and tissues. Knockdown of circ_0001786 restrained IC50 values of gefitinib, attenuated the clonogenic ability and facilitated apoptosis in HCC827-GR and PC9-GR. In addition, circ_0001786 was a molecular sponge for miR-34b-5p. Silencing miR-34b-5p rescued the inhibitory impact of circ_0001786 knockdown on IC50 and cell cloning ability. Moreover, miR-34b-5p directly targeted SRSF1. Importantly, circ_0001786 enhanced gefitinib tolerance and malignant development in NSCLC through miR-34b-5p/SRSF1 pathway. CONCLUSION: This research revealed a novel mechanism by which circ_0001786 enhanced NSCLC resistance to gefitinib by sponging miR-34b-5p and upregulating SRSF1. circ_0001786 was a potential target for improving the treatment of gefitinib-resistant NSCLC patients.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

Echocardiographic measures of the left heart and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: The CABLE study.

INTRODUCTION: This study delineated the interrelationships between subclinical alterations in the left heart, cerebrospinal fluid (CSF), Alzheimer's disease (AD) biomarkers, and cognition. METHODS: Multiple linear regressions were conducted in 1244 cognitively normal participants (mean age = 65.5; 43% female) who underwent echocardiography (left atrial [LA] and left ventricular [LV] morphologic or functional parameters) and CSF AD biomarkers measurements. Mediating effects of AD pathologies were examined. Differences in cardiac parameters across ATN categories were tested using analysis of variance (ANOVA) and logistic regressions. RESULTS: LA or LV enlargement (characterized by increased diameters and volumes) and LV hypertrophy (increased interventricular septal or posterior wall thickness and ventricular mass) were associated with higher CSF phosphorylated (p)-tau and total (t)-tau levels, and poorer cognition. Tau pathologies mediated the heart-cognition relationships. Cardiac parameters were higher in stage 2 and suspected non-Alzheimer's pathology groups than controls. DISCUSSION: These findings suggested close associations of subclinical cardiac changes with tau pathologies and cognition. HIGHLIGHTS: Various subclinical alterations in the left heart related to poorer cognition. Subclinical cardiac changes related to tau pathologies in cognitively normal adults. Tau pathologies mediated the heart-cognition relationships. Subclinical cardiac changes related to the AD continuum, especially to stage 2. The accumulation of cardiac alterations magnified their damage to the brain.

A multi-objective optimized OLSR routing protocol.

The rapid development of mobile communication devices has brought challenges to wireless networks, where data packets are able to organize and maintain local area networks more freely without the constraints of wired devices. Scholars have developed diverse network protocols on how to ensure data transmission while maintaining its self-organizational nature. However, it is difficult for traditional network protocols to meet the needs of increasingly complex networks. In order to solve the problem that the better node set may not be selected when selecting the node set responsible for forwarding in the traditional OLSR protocol, a multi-objective optimized OLSR algorithm is proposed in this paper, which incorporating a new MPR mechanism and an improved NSGA-II algorithm. In the process of route discovery, the intermediate nodes responsible for forwarding packets are determined by the new MPR mechanism, and then the main parameters in the OLSR protocol are provided by the multi-objective optimization algorithm. Matlab was used to build a self-organizing network in this study. In addition, the conventional OLSR protocol, NSGA-II algorithm and multi-objective simulated annealing algorithm are selected to compare with the proposed algorithm. Simulation results show that the proposed algorithm can effectively reduce packet loss and end-to-end delay while obtaining better results in HV and Spacing, two multi-objective optimization result evaluation metrics.

Spiritual Needs and Influencing Factors of Postoperative Breast Cancer Women Undergoing Chemotherapy: A Cross-Sectional Study.

Purpose: The purpose of the study was to determine the status of spiritual needs and influencing factors of postoperative breast cancer (BC) women undergoing chemotherapy. Participants and Methods: This study is a cross-sectional study. A total of 173 participants completed a general information questionnaire and a Chinese version of the Spiritual Needs Scale at the Guangxi Medical University Cancer Hospital. Data were collected by purposive sampling from December 2022 to April 2023. Data were analyzed by descriptive statistics, independent t-test, ANOVA, non-parametric test, and logistic regression analysis. Results: The spiritual needs of postoperative BC women undergoing chemotherapy were at a high level (84.20 ± 12.86). The need for "hope and peace" was considered paramount and the need for a "relationship with transcendence" was considered the least important. Significant differences were found in the following: spiritual needs total score (P=0.040) and "hope and peace" (P=0.021) in education level; "love and connection" in disease stage (P=0.021); "meaning and purpose" in education level (P=0.013), household income (P=0.012), and payment method (P=0.015); "relationship with transcendence" in religion (P<0.001); and "acceptance of dying" in marital status (P=0.023). The level of education was the influencing factor of spiritual needs (OR=1.50, P=0.005), especially for "hope and peace" (OR=1.50, P=0.012). Conclusion: The spiritual need of postoperative BC Chinese women undergoing chemotherapy is at a high level and should receive more attention. In clinical work, nurses should fully assess the spiritual needs of patients and meet their specific needs. Results may help nurses to develop targeted and comprehensive spiritual intervention strategies according to the characteristics of patients.

Photocatalytic Z/E isomerization unlocking the stereodivergent construction of axially chiral alkene frameworks.

The past century has witnessed a large number of reports on the Z/E isomerization of alkenes. However, the vast majority of them are still limited to the isomerization of di- and tri-substituted alkenes. The stereospecific Z/E isomerization of tetrasubstituted alkenes remains to be an underdeveloped area, thus lacking in a stereodivergent synthesis of axially chiral alkenes. Herein we report the atroposelective synthesis of tetrasubstituted alkene analogues by asymmetric allylic substitution-isomerization, followed by their Z/E isomerization via triplet energy transfer photocatalysis. In this regard, the stereodivergent synthesis of axially chiral N-vinylquinolinones is achieved efficiently. Mechanistic studies indicate that the benzylic radical generation and distribution are two key factors for preserving the enantioselectivities of axially chiral compounds.

Host-Guest Recognition-Mediated Supramolecular Aggregation-Induced Electrochemiluminescence of Iridium(III) Complexes for Nucleic Acid Bioassay.

Currently reported aggregation-induced electroluminescence (AIECL) is usually based on the electrostatic integration of luminous monomers, and its application is still limited by the low ECL efficiency and poor structural stability of electrostatic integration-based AIECL emitters. Herein, host-guest recognition-mediated supramolecular AIECL was creatively developed to overcome the defects of electrostatic-integration-based AIECL. Cucurbit[8]uril (CB[8]) as the host recognized tris (2-phenylpyridine) iridium(III) [Ir(ppy)3] as the guest to form a novel supramolecular complex Ir-CB[8]. CB[8] can not only provide a large hydrophobic cavity to efficiently load Ir(ppy)3 and enrich coreactant tripropylamine but also utilize its carbonyl-laced portals to form intramolecular hydrogen bonds to stabilize the supramolecular structure, so Ir-CB[8] revealed excellent AIECL performance. The AIECL emitter Ir-CB[8] coupled the efficient DNA walker to construct a sensing system for miRNA-16 detection. Au nanoparticles@norepinephrine (AuNPs@NE) trapped by single-strand S1 was developed to significantly quench the ECL emission of Ir-CB[8]. When the target microRNA-16 (miRNA-16) existed, H1 was opened and the sequential assembly from H2 to H7 was triggered, forming "windmill"-like DNA walker with six Pb2+-dependent leg DNA. The assembled DNA walker, which was centered on DNA structure, had high efficiency and biocompatibility and can cut S1 to keep the DNA fragment-carrying quencher AuNPs@NE away from the electrode surface, thus restoring the ECL emission of Ir-CB[8] and realizing ultrasensitive detection of miRNA-16. Supramolecular AIECL mediated by host-guest recognition provides a new way for constructing AIECL emitters with excellent structural stability and AIECL efficiency, and an Ir-CB[8] coupling "windmill"-like DNA walker builds a promising ECL-sensing system for bioassay.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration.

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder.

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

SIRT3 negatively regulates TFH cell differentiation in cancer.

Follicular helper T (TFH) cells are essential for inducing germinal center (GC) reactions to mediate humoral adaptive immunity in tumors, but the mechanisms underlying TFH cell differentiation remain unclear. Here, we found that the metabolism sensor sirtuin 3 (SIRT3) is critical for TFH cell differentiation and GC formation during tumor and viral infection. SIRT3 deficiency in CD4+ T cells intrinsically enhanced TFH cell differentiation and GC reactions during tumor and virus infection. Mechanistically, damaged oxidative phosphorylation (OXPHOS) compensatively triggered the NAD+-glycolysis pathway to provide a cellular energy supply, which was necessary for SIRT3 deficiency-induced TFH cell differentiation. Blocking NAD+ synthesis-glycolysis signaling or recovering OXPHOS activities reversed the TFH cell differentiation induced by SIRT3 deficiency. Moreover, the mTOR and HIF1α signaling axis was found to be responsible for TFH cell differentiation induced by SIRT3 deficiency. HIF1α directly interacted with and regulated the activity of the transcription factor Bcl-6. Thus, our findings identify a cellular energy compensatory mechanism, regulated by the mitochondrial sensor SIRT3, that triggers NAD+-dependent glycolysis during mitochondrial OXPHOS injuries and a mTOR-HIF1α-Bcl-6 pathway to reprogram TFH cell differentiation. These data have implications for future cancer immunotherapy research targeting SIRT3 in T cells.

Metagenomic next-generation sequencing for the diagnosis of neurobrucellosis.

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.

Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.