The therapeutic potential of circular RNA in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of the disease that does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Circular RNAs (circRNAs) are a type of non-coding RNA with a circular shape formed by non-standard splicing or reverse splicing. Numerous circRNAs exhibit abnormal expression in various malignancies, showing their critical role in the emergence and growth of tumors. Recent studies have shown evidence supporting the idea that certain circRNAs regulate the proliferation and metastasis of TNBC. In addition, circRNAs alter metabolism and the immune microenvironment to promote or inhibit the development of TNBC. Notably, circRNAs may affect the efficacy of clinical drug therapy, serve as therapeutic targets, and be used as molecular biomarkers in the future. Herein, we will first summarize the biogenesis and function of circRNAs. Then, we will explain current research on circRNAs related to TNBC and their potential to serve as therapeutic targets or biomarkers for future drug development, providing a new direction and idea for TNBC therapy.

Plasma EBV quantification is associated with the efficacy of immune checkpoint blockade and disease monitoring in patients with primary pulmonary lymphoepithelioma-like carcinoma.

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

Interpersonal Sensitivity and Subjective Well-Being of Migrant Workers' Accompanying Children: Role of Perception of Exclusion and Peer Support.

Introduction: To investigate the impact of interpersonal sensitivity on the subjective well-being of accompanying children of migrant workers and the role of perception of exclusion and peer support in the process. Methods: A questionnaire survey was conducted among 304 migrant workers' accompanying children and 501 urban children in grades 4-9 in seven schools in Jiangxi Province, China. Hierarchical regression and bootstrap analysis were used. Results: Interpersonal sensitivity not only had a significant direct negative effect on the subjective well-being of migrant workers' accompanying children (ß= -0.27, 95% CI = [-0.37, -0.17]), but also had an indirect effect through perception of exclusion (ß= -0.06, 95% CI = [-0.11, -0.03]). Peer support negatively moderated the relationship between interpersonal sensitivity and perception of exclusion (ß= -0.18, 95% CI = [-0.28, -0.08]) and the mediating effect of perceptions of exclusion between interpersonal sensitivity and subjective well-being (ß = 0.06, CI = [0.02, 0.11]). Conclusion: The subjective well-being of migrant children is indeed lower than that of urban children, and one of the most important reasons is their higher interpersonal sensitivity. Interpersonal sensitivity not only directly reduces their subjective well-being, but also reduces it by triggering their perception of exclusion, while peer support can effectively mitigate this negative effect. Therefore, one way to improve the subjective well-being of these children is to reduce their excessive interpersonal sensitivity. Their parents should help them to adapt to urban life, to develop correct professional values and to deal correctly with "occupational stigma", to overcome feelings of inferiority, while communities can create specialized activity centers to provide more social opportunities and psychological counseling services for these children.

Analysis of PD-1/PD-L1 variations in lung cancer and association with immunotherapeutic efficacy and prognosis: A nonrandomized controlled trial.

INTRODUCTION: This study aims to explore Programmed Death Receptor-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) variations in Lung Cancer (LC) tissues and Peripheral Blood (PPB) and their association with immunotherapy efficacy and prognosis. METHOD: 72 patients with LC were included in the LC group and 39 patients with concurrent benign lung disease were included in the benign group. PD-1/PDL-1 was compared in PPB and lung tissue. All LC patients were treated with immunotherapy. The relationship between PD-1/PDL-1 in LC tissue and PPB and immunotherapy efficacy was analyzed. Patients were divided into death and survival groups, and PD-1/PDL-1 in tumor tissues and PPB were compared. RESULTS: The authors found that PD-1 and PDL-1 positive expression in lung tissue and PPB in LC patients was elevated. Combined detection of PD-1 and PDL-1 was effective in diagnosing LC and evaluating the prognosis of LC patients. PD-1 and PDL-1 positive expression was reduced after disease remission while elevated in dead patients. The 3-year survival rate of patients with PD-1 positive expression was 45.45 % (25/55), which was lower (82.35 %, 14/17) than those with PD-1 negative expression. The 3-year survival rate of patients with positive and negative expression of PDL-1 was 48.78 % (20/41) and 61.29 % (19/31), respectively. DISCUSSION: The present results demonstrated that PD-1 and PDL-1 are abnormal in cancer tissue and PPB of LC patients. The combined detection of PD-1 and PDL-1 has diagnostic value for LC and evaluation value for the efficacy and prognosis of immunotherapy.

Silica nanoparticles containing nano-silver and chlorhexidine to suppress Porphyromonas gingivalis biofilm and modulate multispecies biofilms toward healthy tendency.

Objectives: This research first investigated the effect of mesoporous silica nanoparticles (nMS) carrying chlorhexidine and silver (nMS-nAg-Chx) on periodontitis-related biofilms. This study aimed to investigate (1) the antibacterial activity on Porphyromonas gingivalis (P. gingivalis) biofilm; (2) the suppressing effect on virulence of P. gingivalis biofilm; (3) the regulating effect on periodontitis-related multispecies biofilm. Methods: Silver nanoparticles (nAg) and chlorhexidine (Chx) were co-loaded into nMS to form nMS-nAg-Chx. Inhibitory zone test and minimum inhibitory concentration (MIC) against P. gingivalis were tested. Growth curves, crystal violet (CV) staining, live/dead staining and scanning electron microscopy (SEM) observation were performed. Biofilm virulence was assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Quantitative Real Time-PCR (qPCR) were performed to validate the activity and composition changes of multispecies biofilm (P. gingivalis, Streptococcus gordonii and Streptococcus sanguinis). Results: nMS-nAg-Chx inhibited P. gingivalis biofilm dose-dependently (p<0.05), with MIC of 18.75 µg/mL. There were fewer live bacteria, less biomass and less virulence in nMS-nAg-Chx groups (p<0.05). nMS-nAg-Chx inhibited and modified periodontitis-related biofilms. The proportion of pathogenic bacteria decreased from 16.08 to 1.07% and that of helpful bacteria increased from 82.65 to 94.31% in 25 µg/mL nMS-nAg-Chx group for 72 h. Conclusions: nMS-nAg-Chx inhibited P. gingivalis growth, decreased biofilm virulence and modulated periodontitis-related multispecies biofilms toward healthy tendency. pH-sensitive nMS-nAg-Chx inhibit the pathogens and regulate oral microecology, showing great potential in periodontitis adjunctive therapy.

Intermittent blood flow restriction with low-load resistance training for older adults with knee osteoarthritis: a randomized, controlled, non-inferiority trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.

Schadenfreude or empathy? Children's emotional responses to the physical pain and pleasure of prosocial and antisocial others.

Adults' emotional reactions to the pain and pleasure of others are influenced by the moral character of those individuals. However, it remains unclear whether children's emotional responses also show such selectivity. To investigate this, we compared 4- to 8-year-old children's emotional responses to the physical pain and pleasure of prosocial versus antisocial puppets. In Study 1, children reported unhappiness after witnessing the pain of the prosocial and antisocial puppets but reported less unhappiness after witnessing the pain of the antisocial puppet. In Study 2, children reported happiness after witnessing the pleasure of both puppets but reported being less happy for the antisocial puppet. These results suggest that children are less likely to empathize with antisocial individuals. Meanwhile, children did not display Schadenfreude (pleasure at others' pain) or Gluckschmerz (displeasure at others' pleasure) toward antisocial individuals in our studies. Moreover, the selectivity of children's emotional responses disappeared after we manipulated the physical competence rather than the moral character of the puppets in Study 3. Our findings help to reveal the moral selectivity of emotional responses to others' pleasure and pain during early childhood.

Inhibiting mitochondrial citrate shuttling induces hepatic triglyceride deposition in Nile tilapia (Oreochromis niloticus) through lipid anabolic remodeling.

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for six weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for seven days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

RNAi-mediated knockdown of papilin gene affects the egg hatching in Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

Efficacy of the 'Five-Needle' method for pancreatojejunostomy in laparoscopic pancreaticoduodenectomy: an observational study.

Objective: The five-needle pancreato-intestinal anastomosis method is used in laparoscopic pancreaticoduodenectomy (LPD). The aim of this study was to explore the clinical efficacy and adverse reactions of this new surgical method and to provide a scientific reference for promoting this new surgical method in the future. Methods: A single-centre observational study was conducted to evaluate the safety and practicality of the five-needle method for pancreatojejunostomy in LPD surgeries. The clinical data of 78 patients who were diagnosed with periampullary malignancies and underwent LPD were collected from the 1st of August 2020 to the 31st of June 2023 at Lanzhou University First Hospital. Forty-three patients were treated with the 'Five-Needle' method (test groups), and 35 patients were treated with the 'Duct-to-Mucosa' method (control group) for pancreatojejunostomy. These two methods are the most commonly used and highly preferred pancreatointestinal anastomosis methods worldwide. The primary outcome was pancreatic fistula, and the incidence of which was compared between the two groups. Results: The incidence of pancreatic fistula in the five-needle method group and the duct-to-mucosa method group was not significantly different (25.6% vs. 28.6%, p=0.767). Additionally, there were no significant differences between the two groups in terms of intraoperative blood loss (Z=-1.330, p=0.183), postoperative haemorrhage rates (p=0.998), length of postoperative hospital stay (Z=-0.714, p=0.475), bile leakage rate (p=0.745), or perioperative mortality rate (p=0.999). However, the operative time in the 'Five-Needle' method group was significantly shorter than that in the 'Duct-to-Mucosa' method group (270 ± 170 mins vs. 300 ± 210 mins, Z=-2.336, p=0.019). Further analysis revealed that in patients with pancreatic ducts smaller than 3 mm, the incidence of pancreatic fistula was lower for the 'Five-Needle' method than for the 'Duct-to-Mucosa' method (12.5% vs. 53.8%, p=0.007). Conclusion: The five-needle method is safe and efficient for pancreatojejunostomy in LPD, and is particularly suitable for anastomosis in nondilated pancreatic ducts. It is a promising, valuable, and recommendable surgical method worthy of wider adoption.

High-order QAM NANF transmission utilizing MIMO equalizer integrated with low-complexity decision-directed carrier phase estimation.

We experimentally realized a high-speed nested anti-resonant nodeless fiber (NANF) transmission with the assistance of the polarization division multiplexing (PDM) and probabilistic shaping (PS) technology. In this system, a low-complexity multiple-input multiple-output (MIMO) real-valued equalizer (RVE) is integrated with decision-directed carrier phase estimation (DDCPE), which is robust against the IQ cross talk and a tiny phase disturbance between PS symbols. By using the proposed MIMO-RVEDDCPE, the 60-Gbaud PDM-PS-256QAM signal has been delivered through 2-km NANF satisfying the soft-decision forward error correction (SD-FEC) threshold.

m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Oral immunotherapy with enteric-coated capsules for allergic rhinitis caused by house dust mites.

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites. Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated. Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group. Conclusion: OIT is an effective and safe treatment for mite-induced AR.

K-means non-uniform-quantization digital-analog radio-over-fiber scheme for THz-band photonics-aided wireless fronthaul.

We propose a non-uniform-quantization digital-analog radio-over-fiber (NUQ-DA-RoF) scheme based on an advanced K-means NUQ algorithm and demonstrate it experimentally in a 2-m 300-GHz photonics-aided wireless fronthaul system. Results show that the NUQ-DA-RoF scheme achieves a SNR gain of ∼1.9 dB compared to the uniform-quantization DA-RoF (UQ-DA-RoF) at an equivalent Common Public Radio Interface equivalent data rate (CPRI-EDR). Remarkably, the NUQ-DA-RoF scheme exhibits an ∼1.6-dB power sensitivity enhancement over the UQ-DA-RoF at the 256-QAM SNR threshold. These findings highlight the advantages of the NUQ-DA-RoF scheme over UQ-DA-RoF in terms of power budget and SNR improvement, suggesting promising prospects for future radio access networks and wireless fronthaul.

The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy.

Background: IgA nephropathy (IgAN), the most common type of glomerulonephritis, has great individual differences in prognosis. Many studies showed the relationship between thyroid hormones and chronic kidney disease. However, the relationship between free thyroxine (FT4), as a thyroid hormone, and IgAN is still unclear. This study aimed to evaluate the impact of FT4 on IgAN prognosis. Methods: This retrospective study involved 223 patients with biopsy-proven IgAN. The renal composite outcomes were defined as: (1) ESRD, defined as eGFR < 15 ml/(min·1.73 m2) or initiation of renal replacement therapy (hemodialysis, peritoneal dialysis, renal transplantation); (2) serum creatinine doubled from baseline; (3) eGFR decreased by more than 50% from baseline. The predictive value was determined by the area under the curve (AUC). Kaplan-Meier and Cox proportional hazards analyses assessed renal progression and prognosis. Results: After 38 (26-54) months of follow-up, 23 patients (10.3%) experienced renal composite outcomes. Kaplan-Meier survival curve analysis showed that the renal survival rate of the IgAN patients with FT4<15.18pmol/L was lower than that with FT4≥15.18pmol/L (P < 0. 001). Multivariate Cox regression model analysis showed that FT4 was a protective factor for poor prognosis of IgAN patients, whether as a continuous variable or a categorical variable (HR 0.68, 95%CI 0.51-0.90, P =0.007; HR 0.04, 95%CI 0.01-0.20, P <0.001). ROC curve analysis showed that FT4 combined with t score had a high predictive value for poor prognosis of IgAN patients (AUC=0.881, P<0.001). Conclusion: FT4 was a protective factor for IgAN. In addition, FT4 combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN.

Antimicrobial activity and structure-activity relationships of molecules containing mono- or di- or oligosaccharides: An update.

Bacterial infections are the second leading cause of death worldwide, and the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens exacerbate the threat crisis. Carbohydrates participate in bacterial infection, drug resistance and the process of host immune regulation. Numerous antimicrobials derived from carbohydrates or contained carbohydrate scaffolds that are conducive to an increase in pathogenic bacteria targeting, the physicochemical properties and druggability profiles. In the paper, according to the type and number of sugar residues contained in antimicrobial molecules collected from the literatures ranging from 2014 to 2024, the antimicrobial activities, action mechanisms and structure-activity relationships were delineated and summarized, for purpose to provide the guiding template to select the type and size of sugars in the design of oligosaccharide-based antimicrobials to fight the looming antibiotic resistance crisis.

Fluid-Solid Interfacial Properties and Drag-Reducing Characterization of the Flexible Conical Microstructured Film Inspired by the Streamlined Body Surface of the Pufferfish.

Given the challenges in accurately replicating the surface of the pufferfish, this study employed three-dimensional (3D) printing to create a model based on inverse modeling. The morphology of the pufferfish exhibits a streamlined configuration, characterized by a gradual widening from the anterior oral region to the central ocular area, followed by a progressive narrowing from the midabdominal region toward the caudal extremity. The RNG k-ε turbulence simulation results demonstrate that the streamlined body surface of the pufferfish diminishes differential pressure resistance. This enhancement promotes laminar flow formation, delays fluid separation, minimizes turbulence-induced vortices, and reduces frictional resistance. Moreover, the pufferfish's supple and uneven outer epidermis was simplified into a flexible, nonsmooth planar film to conduct fluid-solid coupling simulations. These revealed that the pufferfish's unique skin can absorb turbulent energy and minimize momentum transfer between the fluid and the solid film, lowering the fluid resistance during swimming. In summary, The high-efficiency swimming capacity of pufferfish stems not only from their streamlined body surface but also significantly from the unique structural characteristics and mechanical properties of their flexible skin. This research provides critical theoretical underpinnings for the design of functional bionic surfaces aimed at drag reduction.

The Complexity of Neuropathic Pain and Central Sensitization: Exploring Mechanisms and Therapeutic Prospects.

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.

Cell-free assays reveal the HIV-1 capsid protects reverse transcripts from cGAS.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system. We found that wild-type HIV-1 capsids protect their genomes from cGAS even after completion of reverse transcription. Viral DNA could be "deprotected" by thermal stress, capsid mutations, or reduced concentrations of inositol hexakisphosphate (IP6) that destabilize the capsid. Strikingly, capsid inhibitors also disrupted viral cores and dramatically potentiated cGAS activity, both in vitro and in cellular infections. Our results provide biochemical evidence that the HIV-1 capsid lattice conceals the genome from cGAS and that chemical or physical disruption of the viral core can expose HIV-1 DNA and activate innate immune signaling.