Earthworms improve the rhizosphere micro-environment to mitigate the toxicity of microplastics to tomato (Solanum lycopersicum).

Microplastics (MPs) are widespread in agricultural soil, potentially threatening soil environmental quality and plant growth. However, toxicological research on MPs has mainly been limited to individual components (such as plants, microbes, and animals), without considering their interactions. Here, we examined earthworm-mediated effects on tomato growth and the rhizosphere micro-environment under MPs contamination. Earthworms (Eisenia fetida) mitigated the growth-inhibiting effect of MPs on tomato plant. Particularly, when exposed to environmentally relevant concentrations (ERC, 0.02% w/w) of MPs, the addition of earthworms significantly (p < 0.05) increased shoot and root dry weight by 12-13% and 13-14%, respectively. MPs significantly reduced (p < 0.05) soil ammonium (NH4+-N) (0.55-0.69 mg/kg), nitrate nitrogen (NO3--N) (7.02-8.65 mg/kg) contents, and N cycle related enzyme activities (33.47-42.39 µg/h/g) by 37.7-50.9%, 22.6-37.2%, and 34.2-48.0%, respectively, while earthworms significantly enhanced (p < 0.05) inorganic N mineralization and bioavailability. Furthermore, earthworms increased bacterial network complexity, thereby enhancing the robustness of the bacterial system to resist soil MPs stress. Meanwhile, partial least squares modelling showed that earthworms significantly influenced (p < 0.01) soil nutrients, which in turn significantly affected (p < 0.01) plant growth. Therefore, the comprehensive consideration of soil ecological composition is important for assessing MPs ecological risk.

Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol.

Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.

Effectiveness of a school-based Life Gatekeeper Training Program on suicide prevention in China: protocol for a randomized controlled trial.

BACKGROUND: With suicide as a leading cause of death, the issue of children and adolescent suicide risks is in the spotlight today. To empower teachers in primary and secondary schools to serve as gatekeepers and to ensure the safety of children and adolescents, the systematically tailored and localized Life Gatekeeper suicide prevention program was designed for Chinese schools. OBJECTIVE: With the ultimate goal of preventing child and adolescent suicide, we aim to outline a research protocol for examining outcomes of the recently created standardized school-based Life Gatekeeper program in reducing teachers' stigma, increasing their knowledge, willingness to intervene, and perceived competence. METHODS: Participants will be recruited from eligible primary and secondary schools. Cluster sampling will be used to randomly assign each school to either the intervention group or the control group. The primary outcomes are stigma against suicide, suicide literacy, perceived competence, and willingness to intervene with suicidal individuals, which will be measured using the Stigma of Suicide Scale, the Literacy of Suicide Scale, and the Willingness to Intervene Against Suicide Questionnaire, respectively. Measurements will be taken at four time points, including pre-intervention, immediately after the intervention, 6-month follow-up, and 1-year follow-up. CONCLUSIONS: The current study features innovative implementation in the real world, by using a randomized controlled trial design to examine the effectiveness of a school-based gatekeeper program among primary and secondary school teachers, following a sequence of defined and refined steps. The research will also investigate the viability of a school-based gatekeeper program for primary and secondary school teachers that could be quickly and inexpensively implemented in a large number of schools.

Benefit analysis of the auto-verification system of intelligent inspection for microorganisms.

In recent years, the automatic machine for microbial identification and antibiotic susceptibility tests has been introduced into the microbiology laboratory of our hospital, but there are still many steps that need manual operation. The purpose of this study was to establish an auto-verification system for bacterial naming to improve the turnaround time (TAT) and reduce the burden on clinical laboratory technologists. After the basic interpretation of the gram staining results of microorganisms, the appearance of strain growth, etc., the 9 rules were formulated by the laboratory technologists specialized in microbiology for auto-verification of bacterial naming. The results showed that among 70,044 reports, the average pass rate of auto-verification was 68.2%, and the reason for the failure of auto-verification was further evaluated. It was found that the main causes reason the inconsistency between identification results and strain appearance rationality, the normal flora in the respiratory tract and urine that was identified, the identification limitation of the mass spectrometer, and so on. The average TAT for the preliminary report of bacterial naming was 35.2 h before, which was reduced to 31.9 h after auto-verification. In summary, after auto-verification, the laboratory could replace nearly 2/3 of manual verification and issuance of reports, reducing the daily workload of medical laboratory technologists by about 2 h. Moreover, the TAT on the preliminary identification report was reduced by 3.3 h on average, which could provide treatment evidence for clinicians in advance.

A serial mediating effect of perceived family support on psychological well-being.

Family has a significant impact on individual mental health. Based on social support theory, family system theory and the Mental Health Continuum Short Form (MHC-SF), this research constructed a model of the pathway of perceived family support on psychological well-being and the results empirically clarified that perceived family support has a significant positive relationship with emotional well-being, social well-being, and psychological well-being (P < 0.001). Emotional well-being positively influences social well-being and psychological well-being (P < 0.001). Social well-being positively affects psychological well-being (P < 0.001). There were direct mediating effects of emotional well-being (13.45%), direct mediating effects of social well-being (32.82%) and a serial mediating effect (28.07%) between perceived family support and psychological well-being (P < 0.001).

Myocardial deformation characteristics assessed by cardiovascular magnetic resonance feature tracking in a healthy Chinese population.

Purpose: To explore global/regional myocardial deformation across various layers, vascular distributions, specific levels and distinct walls in healthy individuals using cardiovascular magnetic resonance feature tracking (CMR-FT). Methods: We selected a cohort of 55 healthy participants and CMR cine images were used to obtain the left ventricular (LV) peak longitudinal, circumferential, radial strains (LS, CS, RS). The characteristics of normal LV strain in various layers (endocardium, myocardium, epicardium), territories [left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA)], levels (basal, middle, apical) and walls (anterior, septum, inferior, lateral) were compared. Results: The absolute values of the LV global LS and CS gradually decreased from endocardium to epicardium. The absolute LV global RS (65.7 ± 47.7%) was maximum relative to LS (-22.0 ± 10.8%) and CS (-22.8 ± 7.7%). The absolute values of the LCX territorial strain were the largest compared with the LAD and RCA territorial strains. Regional RS, endo-CS and endo-LS gradually increased from the basal to the apical level. The LV lateral walls had the highest strain values (CS, LS, and RS). Conclusions: Variations in normal LV strain values across various layers, territories, levels, and walls were observed, suggesting the necessity for careful clinical interpretation of these strain values. These findings also partially revealed the complexity of normal cardiac mechanics.

A Novel Perspective on Enhancing Photocatalytic Performance through the Synergistic Effect of Nd Single Atoms and Heterostructures.

There are few reports on lanthanide single atom modified catalysts, as the role of the 4f levels in photocatalysis is difficult to explain clearly. Here, the synergistic effect of 4f levels of Nd and heterostructures is studied by combining steady-state, transient, and ultrafast spectral analysis techniques with DFT theoretical calculations based on the construction of Nd single atom modified black phosphorus/g-C3N4 (BP/CN) heterojunctions. As expected, the generation rates of CO and CH4 of the optimized heterostructure are 7.44 and 6.85 times higher than those of CN, and 8.43 and 9.65 times higher than those of BP, respectively. The Nd single atoms can not only cause surface reconstruction and regulate the active sites of BP, but also accelerate charge separation and transfer, further suppressing the recombination of electron-hole pairs. The electrons can transfer from g-C3N4:Nd to BP:Nd, with a transfer time of ≈11.4 ps, while the radiation recombination time of electron-hole pairs of g-C3N4 is ≈26.13 µs, indicating that the construction of heterojunctions promotes charge transfer. The 2P1/2/2G9/2/4G7/2/2H11/2/4F7/2→4I9/2 emissions from Nd3+ can also be absorbed by heterostructures, which improves the utilization of light. The energy change of the key rate measurement step CO2 *→COOH* decreases through Nd single atom modification.

Microbial-induced carbonate precipitation effectively prevents Pb2+ migration through the soil profile: Lab experiment and model simulation.

Due to the inappropriate disposal of waste materials containing lead (Pb) and irrigation with sewage containing Pb, the migration of Pb2+ within the soil profile has been extensively investigated. The conventional Pb2+ block method is challenging to implement due to its complex operational procedures and high construction costs. To address this issue, this study introduces the microbial-induced carbonate precipitation (MICP) technique as a novel approach to impede the migration of Pb2+ in the soil profile. Soil acclimatization with urea resulted in an increased proportion of urease-producing microorganisms, including Bacillus, Paenibacillus, and Planococcaceae, along with heightened expression of urea-hydrolyzing genes (UreA, UreB, UreC, and UreG). This indicates that urea-acclimatized soil (Soil-MICP) possesses the potential to induce carbonate precipitation. Batch Pb2+ fixation experiments confirmed that the fixation efficiency of Soil-MICP on Pb2+ exceeded that of soil without MICP, attributed to the MICP process within the Soil-MICP group. Dynamic migration experiments revealed that the MICP reaction transformed exchangeable lead into carbonate-bound Pb, effectively impeding Pb2+ migration in the soil profile. Additionally, the migration rate of Pb2+ in Soil-MICP was influenced by varying urea amounts, pH levels, and pore flow rates, leading to a slowdown in migration. The Two-site sorption model aptly described the Pb2+ migration process in the Soil-MICP column. This study aims to elucidate the MICP biomineralization process, uncover the in-situ blocking mechanism of MICP on lead in soil, investigate the impact of Pb on key genes involved in urease metabolism, enhance the comprehension of the chemical morphology of lead mineralization products, and provide a theoretical foundation for MICP technology in preventing the migration of Pb2+ in soil profiles.

Environmental factors influencing the soil-air partitioning of semi-volatile petroleum hydrocarbons: Laboratory measurements and optimization model.

The soil-air partition coefficient (KSA) values are commonly utilized to examine the fate of organic contaminants in soils; however, their measurement has been lacking for semi-volatile petroleum hydrocarbons within soil contaminated by crude oil. This research utilized a solid-phase fugacity meter to determine the KSA values of n-alkanes and polycyclic aromatic hydrocarbons (PAHs) under crucial environmental conditions. The results showed a notable increase in KSA values with the extent of crude oil contamination in soil. Specifically, in the 3 % crude oil treatment, the KSA values for n-alkanes and PAHs increased by 1.16 and 0.66 times, respectively, compared to the 1 % crude oil treatment. However, the KSA values decreased with changes in temperature, water content, and particle size within the specified experimental range. Among these factors, temperature played a significant role. The KSA values for n-alkanes and PAHs decreased by 0.27-0.89 and 0.61-0.83 times, respectively, with a temperature increase from 5 °C to 35 °C. Moreover, the research identified that the molecular weight of n-alkanes and PAHs contributed to variations in KSA values under identical environmental factors. With an increase in temperature from 5 °C to 35 °C, the range of n-alkanes present in the air phase expanded from C11 to C34, and PAHs showed elevated levels of acenaphthene (ACE) and benzo (b) fluoranthene (BbFA). Furthermore, heightened water content and particle size were observed to facilitate the volatilization of low molecular weight petroleum hydrocarbons. The effect of environmental variables on soil-air partitioning was evaluated using the Box-Behnken design (BBD) model, resulting in the attainment of the lowest log KSA values. These results illustrate that soil-air partitioning is a complex process influenced by various factors. In conclusion, this study improves our comprehension and predictive capabilities concerning the behavior and fate of n-alkanes and PAHs within soil-air systems.

Retinal giant cyst treated by the scleral buckling procedure: A case report.

INTRODUCTION: Retinal cysts are rare lesions of the fundus that are essentially fluid-filled cavities located or originating in the retina, with a diameter larger than the normal retinal thickness. To date, there have been few case reports of giant retinal cyst hemorrhage with retinoschisis. CASE PRESENTATION: A 32-year-old woman with no other medical history complained of decreased vision for 3 days after a severe cough. The best-corrected visual acuity in the right eye was 0.5. A comprehensive ophthalmological examination including slit-lamp fundoscopy, ultrasound scan of the eye, optical coherence tomography scan, and orbital magnetic resonance imaging was performed. Ophthalmological examination revealed grade III anterior chamber blood cells and grade III vitreous hemorrhage in the right eye and a large herpetic cyst on the nasal side of the retina. The cyst projected into the vitreous, with a large amount of hemorrhage vaguely visible within it. The cyst was clearly visible, and a superficial retinal limiting detachment was observed around it. Ultrasound showed a retinal cyst with retinal detachment in the right eye. Laboratory test results were unremarkable. After 3 months of conservative treatment, the patient's intracystic hemorrhage was significantly absorbed, but the size of the cyst cavity did not show any significant change. Scleral buckling with external compression combined with external drainage of the intracystic fluid was performed, the patient's visual acuity was gradually restored to a normal 1.0 after the operation, and the retina appeared flattened. The patient was finally diagnosed with a giant retinal cyst with retinoschisis in the right eye. The presumed cause was heavy coughing leading to rupture and hemorrhage of the retinal cyst, similar to the mechanism of rupture of an arterial dissection. To the best of our knowledge, this case of retinal cyst rupture and hemorrhage caused by heavy coughing with good recovery after external surgical treatment has never been reported before. CONCLUSIONS: Giant cystic retinal hemorrhage with retinoschisis is very rare. Orbital magnetic resonance imaging and ocular B-scan ultrasound are essential for its diagnosis, and the selection of an appropriate surgical procedure is necessary to maximize the benefit for affected patients.

SdrR, a LysR-Type Regulator, responds to the mycobacterial antioxidant defense.

Protection against oxidative stress is a vital defense mechanism for Mycobacterium tuberculosis within the host. However, few transcription factors that control bacterial antioxidant defense are known. Here, we present evidence that SdrR, encoded by the MSMEG_5712 (Ms5712) gene, functions as an oxidative stress response regulator in Mycobacterium smegmatis. SdrR recognizes an 11-bp motif sequence in the operon's upstream regulatory region and negatively regulates the expression of short-chain dehydrogenases/reductases (SDR). Overexpressing sdrR inhibited SDR expression, which rendered the strain oxidative more stress-sensitive. Conversely, sdrR knockout alleviates SDR repression, which increases its oxidative stress tolerance. Thus, SdrR responds to oxidative stress by negatively regulating sdr expression. Therefore, this study elucidated an underlying regulatory mechanism behind mycobacterial oxidative stress adaptation.

Efficacy and Safety of Pericapsular Nerve Group Block for Hip Fracture Surgery under Spinal Anesthesia: A Meta-Analysis.

Objective: To evaluate the effectiveness and safety of pericapsular nerve group (PENG) block for hip fracture surgery under spinal anesthesia. Methods: This meta-analysis was registered on INPLASY (INPLASY202270005). PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched to collect the randomized controlled trials of the PENG block applied to hip fracture surgery in the setting of spinal anesthesia, with the search period from inception to 1 May 2023. Two independent researchers gradually screened the literature, evaluated the quality, extracted the data, and eventually pooled data using RevMan 5.4. Results: Fifteen articles with 890 patients were enrolled. The combined results showed that the PENG block reduced pain scores during position placement (SMD = -0.35; 95% CI [-0.67, 0.02]; P=0.04; I2 = 0%). Subgroup analyses showed that compared to the unblocked group, the PENG block reduced pain scores at 12 h, 24 h, and 48 h postoperatively. The incidence of postoperative hypokinesia was reduced (RR = 0.11; 95% CI [0.01, 0.86]; P=0.04; I2 = 0.00%). The time to first walking was advanced (SMD = -0.90; 95% CI [-1.17, 0.63]; P < 0.00001; I2 = 0%). Conclusion: The PENG block can reduce postoperative pain and pain during spinal anesthesia positioning, which is helpful to improve the operability and comfort of spinal anesthesia and facilitate postoperative muscle strength recovery and early activity.

[Preparation of Chitosan-modified Biochar and Its Adsorption Mechanism for Cd2+ in Aqueous Solution].

Chitosan-modified biochar （CBC） was prepared as a low-cost and highly efficient adsorbent for Cd2+ in aqueous solutions. Batch adsorption experiments were conducted to evaluate the adsorption performance. Characterization experiments with SEM-EDS， FTIR， and XPS were used to analyze the surface microstructure and chemical composition of the adsorbent. The results showed that the adsorption performance of CBC was remarkably improved by the introduction of surface functional groups （-OH， -C=O， and -NH2）. The pseudo-second-order kinetic model and Langmuir model were better for describing the kinetics and isotherms for Cd2+ adsorption onto CBC， indicating that the adsorption rate was determined by the active sites and controlled by monolayer chemisorption. The adsorption process was endothermic spontaneous， and the key mechanisms involved complexation， precipitation， cation exchange， and cation-π bonds. After five instances of adsorption-desorption cycles， the adsorption capacity of CBC for Cd2+ still remained above 80% of the initial adsorption capacity， indicating that CBC had a favorable recyclability. The current work embodies the concept of green chemistry， and the prepared chitosan-modified biochar was a promising adsorbent for the removal of Cd2+ in wastewater and soil.

Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides an aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

Three chemosensory proteins enriched in antennae and tarsi of Rhaphuma horsfieldi differentially contribute to the binding of insecticides.

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.

A 49-Year-Old Man With Fever and Dyspnea After Endobronchial Ultrasound-Guided Transbronchial Fine Needle Aspiration Biopsy.

CASE PRESENTATION: A 49-year-old man, a farmer, had been experiencing coughing, phlegm, and difficulty breathing for 2 months. He underwent a CT scan at a local hospital that showed a mediastinal mass. Bronchoscopy showed no obstruction in the tracheal lumen, and an endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) biopsy was performed on the mediastinal mass. The cytologic smear of the mediastinal mass showed a few atypical epithelial cells; the possibility of a tumor could not be ruled out. The patient visited our thoracic surgery outpatient department; based on the advice of the thoracic surgeon, the patient underwent another endobronchial ultrasound-guided transbronchial fine needle aspiration biopsy of the mediastinal mass 4 days before this admission. The patient went home and waited for the results. Two days later, the patient experienced a fever and palpitations accompanied by chills, yellow phlegm, and orthopnea. The patient visited our ED, underwent tracheal intubation, and was admitted to our ICU. The patient had had occasional coughing and phlegm for the past 10 years, which were not taken seriously or investigated. The patient does not smoke or drink alcohol, and there is no history of cancer in the family.

Interleukin-4 from curcumin-activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti-inflammatory activity for functional repair of spinal cord injury.

Microglia/macrophages are major contributors to neuroinflammation in the central nervous system (CNS) injury and exhibit either pro- or anti-inflammatory phenotypes in response to specific microenvironmental signals. Our latest in vivo and in vitro studies demonstrated that curcumin-treated olfactory ensheathing cells (aOECs) can effectively enhance neural survival and axonal outgrowth, and transplantation of aOECs improves the neurological outcome after spinal cord injury (SCI). The therapeutic effect is largely attributed to aOEC anti-inflammatory activity through the modulation of microglial polarization from the M1 to M2 phenotype. However, very little is known about what viable molecules from aOECs are actively responsible for the switch of M1 to M2 microglial phenotypes and the underlying mechanisms of microglial polarization. Herein, we show that Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers IL­1ß, IL­6, tumour necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) and elevating the levels of M2 markers Arg-1, TGF-ß, IL-10, and CD206. Strikingly, blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth. In addition, transplantation of aOECs improved the neurological function deficits after SCI in rats. More importantly, the crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event. These results provide new insights into the molecular mechanisms of aOECs driving the M1-to-M2 shift of microglia and shed light on new therapies for SCI through the modulation of microglial polarization.

The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.

Real-world data of China: Analysis of HPV vaccine coverage and post-vaccination adverse reaction monitoring in Western Chinese provinces from 2018 to 2021.

To investigate the HPV vaccine coverage and post-vaccination adverse reactions in Gansu Province, Western China, from 2018 to 2021. Data on suspected adverse reactions to HPV vaccines were collected from the Chinese Vaccine Adverse Event Following Immunization (AEFI). Estimate the incidence rates of Common Adverse Reaction and Rare Adverse Reaction. HPV vaccine coverage among females in different age groups was calculated using data from the Gansu Provincial Immunization Information Platform. The first-dose HPV vaccine coverage rate among females aged 9 to 45 was 2.02%, with the lowest rate of less than 1% observed in females aged 9 to 14. From 2018 to 2021, the incidence rates of Common Adverse Reaction and Rare Adverse Reaction reported in females after HPV vaccination were 11.82 and 0.39 per 100,000 doses, respectively. Common Adverse Reaction included fever (5.52 per 100,000 doses), local redness and swelling (3.33 per 100,000 doses), fatigue (3.15 per 100,000 doses), headache (2.76 per 100,000 doses), as well as local induration and nausea/vomiting (1.97 per 100,000 doses). Adverse reactions mainly occurred within 1 day after vaccination, followed by 1 to 3 days after vaccination. The HPV vaccine coverage rate among females aged 9 to 14 in Gansu Province is remarkably low, and there is an urgent need to enhance vaccine coverage. From 2018 to 2021, the incidence of Adverse reaction Following Immunization HPV vaccination fell within the expected range, indicating the vaccine's safety profile.

Targeted macrophage phagocytosis by Irg1/itaconate axis improves the prognosis of intracerebral hemorrhagic stroke and peritonitis.

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).