Reciprocal regulation of m 6 A modification and miRNA production machineries via phase separation-dependent and -independent mechanisms.

Methyltransferase complex (MTC) deposits N 6-adenosine (m 6 A) onto RNA, whereas microprocessor produces miRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B (MTB) tends to form insoluble condensates with poor activity, with its level monitored by 20S proteasome. Conversely, the microprocessor component SERRATE (SE) forms liquid-like condensates, which in turn promotes solubility and stability of MTB, leading to increased MTC activity. Consistently, the hypomorphic lines expressing SE variants, defective in MTC interaction or liquid-like phase behavior, exhibit reduced m 6 A level. Reciprocally, MTC can recruit microprocessor to MIRNA loci, prompting co-transcriptional cleavage of primary miRNA (pri-miRNAs) substrates. Additionally, pri-miRNAs carrying m 6 A modifications at their single-stranded basal regions are enriched by m 6 A readers, which retain microprocessor in the nucleoplasm for continuing processing. This reveals an unappreciated mechanism of phase separation in RNA modification and processing through MTC and microprocessor coordination.

Habitat fragmentation strongly restricts gene flow in endangered ectomycorrhizal fungal populations: Evidence from Rhizopogon togasawarius, specific to Pseudotsuga japonica, across the entire distribution range.

Habitat fragmentation reduces gene flow, causing genetic differentiation and diversity loss in endangered species through genetic drift and inbreeding. However, the impact of habitat fragmentation on ectomycorrhizal (ECM) fungi remains unexplored, despite their critical roles in forest ecosystems. Here, we investigated the population genetic structure and the demographic history of Rhizopogon togasawarius, the ECM fungus specifically colonizing the host tree Pseudotsuga japonica, across its entire distribution range (>200 km). These two species are designated as endangered species on the IUCN Red List since they are found only in small, fragmented forests in Japan. We analysed 236 R. togasawarius individuals from five remaining populations across the Kii Peninsula and the Shikoku Island, separated by a sea channel. Simple sequence repeat analyses using 20 loci revealed strong genetic differentiation among populations (FST = 0.255), even significant in the nearest population pair separated by a distance of only 8 km (FST = 0.075), indicating extremely limited gene flow between populations. DIYABC-RF analyses implied that population divergence occurred approximately 6000 generations ago between the two regions, and nearly 1500 generations ago between the nearest populations within Shikoku Island, related to past climate events. Because of prolonged genetic isolation, significant inbreeding was confirmed in four of five populations, where effective population sizes became very small (Ne = 9.0-58.0). Although evaluation of extinction risks for microorganisms is challenging, our conservation genetic results indicated that habitat fragmentation increases extinction risk through population genetic mechanisms, and therefore should not be overlooked in biodiversity conservation efforts.

Cell Identity and Spatial Distribution of PD-1/PD-L1 Blockade Responders.

The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis inhibits T cell activity, impairing anti-tumor immunity. Blocking this axis with therapeutic antibodies is one of the most promising anti-tumor immunotherapies. It has long been recognized that PD-1/PD-L1 blockade reinvigorates exhausted T (TEX) cells already present in the tumor microenvironment (TME). However, recent advancements in high-throughput gene sequencing and bioinformatic tools have provided researchers with a more granular and dynamic insight into PD-1/PD-L1 blockade-responding cells, extending beyond the TME and TEX populations. This review provides an update on the cell identity, spatial distribution, and treatment-induced spatiotemporal dynamics of PD-1/PD-L1 blockade responders. It also provides a synopsis of preliminary reports of potential PD-1/PD-L1 blockade responders other than T cells to depict a panoramic picture. Important questions to answer in further studies and the translational and clinical potential of the evolving understandings are also discussed.

Transcriptional Changes Underlying the Degradation of Plant Community in Alpine Meadow Under Seasonal Warming Impact.

Global warming is exhibiting a seasonal trend, while different seasons have different warming variations. However, the impact of seasonal warming on plants remains unclear. This study employed Open Top Chambers (OTCs) to simulate future seasonal warming scenarios in alpine meadow. The study examined plant community dynamics following long-term seasonal warming. The transcriptional and physiological responses of two dominant species (Kobresia pygmaea and Stipa purpurea) were examined. Results suggest that seasonal warming effects are correlated with both the duration of warming and the season which warming occurs. A long annual warming duration, especially growing season warming, made plants confront various stresses. K. pygmaea adopted a stress-avoidance strategy, showing a negative response, and leading to population decline or disappearance. This kind of dieback had also been observed in other Cyperaceae species. Meanwhile, due to positive responses, S. purpurea adopted a stress-tolerance strategy and overcame the impact of warming, partially gained the dominance over Cyperaceae species. Overall vegetation coverage and plant community diversity decreased over the years. These results reveal the impact of seasonal warming to plants, explaining the reasons for changes in plant communities under seasonal warming and providing new insights for future plant conservation under seasonal warming.

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis.

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.

Orienting people-centred disaster shelter planning based on risk assessing with semi-supervised learning.

Climate-related disasters have been escalating worldwide, incurring major losses. Landslides have become one of the most destructive disasters, especially in China's mountainous areas. To address this, constructing emergency shelters and designing evacuation routes are critical to ensure public safety and minimize impacts on affected residents. This study proposes a novel two-phase, people-centric approach. The first phase applies stakeholder theory and risk economics to develop a landslide hazard assessment model considering vulnerable populations. The model effectively classified 28 landslide points in Bazhou Town, with 35.71 % deemed high-risk and low-risk 64.29 %, reflecting the model's comprehensive risk differentiation capability. The second phase utilizes public choice theory to construct a bi-level multiple objective programming (BLMOP) model addressing conflicting government and resident goals. The algorithm produced 4 Pareto-optimal shelter plans for each village assessed, results demonstrate the proposed approach generates shelter plans meeting government aims while maximizing resident satisfaction, accounting for local conditions. Grounded in field data and a people-focused lens, this two-stage methodology provides a multiple objective optimization framework balancing stakeholder need. A case study of Bazhou Town validates the method's effectiveness.

Borderline Developmental Dysplasia of the Hip With Osseous Impingement as Distinct From Femoroacetabular Impingement and Developmental Dysplasia of the Hip.

Background: Borderline developmental dysplasia of the hip (BDDH) accompanied by cam deformity and subspinous impingement has been found to benefit from arthroscopic surgery. However, the research comparing BDDH combined with osseous impingement to femoroacetabular impingement (FAI) without borderline dysplasia remains limited. Purpose/Hypothesis: To compare the clinical symptoms, intraoperative findings, and outcomes of hip arthroscopy in patients with BDDH and osseous impingement versus cam-type FAI. It was hypothesized that BDDH with osseous impingement could be classified as a distinct entity between FAI and developmental dysplasia of the hip (DDH). Study Design: Cohort study; Level of evidence, 3. Methods: Data were collected from patients 18 to 50 years old who underwent primary hip arthroscopy between September 2016 and October 2020. Patients were divided based on preoperative lateral center-edge angle (LCEA) into 2 groups: (1) BDDH group (LCEA 18°-25°; n = 67); and (2) cam-type FAI group without BDDH (FAI group; LCEA 25°-40° and alpha angle >55°; n = 145). Disparities in symptoms, preoperative examination, intraoperative findings and procedures, and patient-reported outcome (PRO) scores were compared. Results: Follow-up was available for 61 (91.0%) patients in the BDDH group and 125 (86.2%) patients in the FAI group. The incidence of cam deformity in BDDH patients was 91.8%. The preoperative characteristics and intraoperative findings were similar between the groups; however, preoperative internal and external hip rotation, Tönnis angle, femoroepiphyseal acetabular roof index, labral size, capsule thickness, and percentage of ligamentum teres tear were significantly higher in the BDDH group than the FAI group, and the percentage of pain aggravating factor, cam deformity, and anterior inferior iliac spine types 2 and 3 were also significantly different between groups (P < .05 for all). The percentage of intraoperative minimal acetabuloplasty, subspinous decompression, labral repair, ligamentum teres debridement, and capsular closure was significantly higher in the BDDH group than the FAI group, while the percentage of femoroplasty was higher in the FAI group (P < .05). Pre- to postoperative improvement on PRO scores was seen in both groups. Conclusion: Given the differences in etiology and surgical procedures between the 2 conditions, it is suggested that BDDH with osseous impingement be classified as an entity distinct from FAI and DDH (and separate from BDDH without impingement) while excluding joint instability.

[Declining Rate of Neural Tube Defects and Outcomes of Defective Infants in Shaanxi Province from 2003 to 2022].

Objective To evaluate the changes in the incidence of neural tube defects (NTDs) in Shaanxi province from 2003 to 2022,investigate the diagnosis time and outcomes of defective infants,and predict the incidence of NTDs in Shaanxi province from 2023 to 2025,thereby providing a basis for improving the birth defects surveillance system. Methods Data were collected from all the perinatal infants from 28 weeks of gestation to 7 days after birth in all the hospitals with obstetrical department in Shaanxi province during 2003-2022.The changes in the incidence of NTDs from 2003 to 2022 were analyzed based on the birth defects surveillance system. Results A total of 1 106 483 perinatal infants in Shaanxi province from 2003 to 2022 were surveyed,among which NTDs occurred in 848 perinatal infants,with an incidence of 7.66/10 000.The incidence was the highest (48.02/10 000) in 2005 and the lowest (0.57/10 000) in 2022.The NTDs in Shaanxi province were mainly spina bifida (55.90%),which was followed by anencephaly (25.71%) and encephalocele (18.40%).The incidences of the three declined with fluctuations (P<0.001).The results of the Joinpoint analysis showed that the incidence of NTDs decreased slowly with the annual percentage change of -4.04 from 2003 to 2014 and declined rapidly with the annual percentage change of -28.05 from 2014 to 2022.From 2003 to 2022,the average proportion of prenatal diagnosis of NTDs in Shaanxi province was 72.88%.Dead fetus (61.91%) was the main birth outcome,followed by live birth (26.77%),stillbirth (8.73%),and death within seven days after birth (2.59%).The incidence of NTDs in Shaanxi province from 2023 to 2025 were predicted by the GM (1,1) model as 0.49/10 000,0.41/10 000,and 0.35/10 000,respectively. Conclusion The incidence of NTDs in Shaanxi province declined significantly during 2003-2022,especially in a rapid manner after 2014.Dead fetus was the primary outcome of perinatal infants with NTDs,followed by live birth.

Female genital prolapse and risk of psychiatric disorders: A two-sample Mendelian randomization analysis.

BACKGROUND: There is a growing body of evidence suggests a strong link between female genital prolapse (FGP) and mental health. However, the causal relationship between FGP and psychological disorders remains unclear. OBJECTIVES: Bidirectional Mendelian Randomization (MR) analysis has been applied to investigate the potential impact of FGP on the risk of seven common psychiatric disorders. METHODS: The two-sample MR analysis was conducted using genetic instruments such as Inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode from the genome-wide association study (GWAS) summary data in European populations. In addition, the Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers (MR-PRESSO) test and leave-one-out analysis were employed to assess the sensitivity and heterogeneity. RESULTS: The MR results revealed that FGP exhibited a potential marginal protective effect on bipolar disorder (BD) (odds ratio(OR) = 0.92, 95%confidence interval (95%CI: 0.85-0.99, P = 0.03) as well as schizophrenia(OR = 0.91, 95%CI:0.85-0.98, P = 0.01). Nevertheless, there was no causal correlation between genetically predicted FGP and obsessive compulsive disorder (OCD) (OR = 0.98, 95%CI:0.80-1.20, P = 0.84),depression (broad) (OR = 1.00, 95%CI:0.99-1.01, P = 0.76), major depression(OR = 0.98, 95%CI:0.94-1.03, P = 0.43), anxiety disorders (OR = 1.00, 95%CI:0.94-1.07,P = 0.97) and post-traumatic stress disorder(PTSD) (OR = 1.18, 95%CI:0.88-1.57,P = 0.27),respectively. In addition, BD was found to have a potential significant influence on FGP in the inverse MR analysis (OR = 0.83, 95%CI:0.72-0.97, P = 0.02). No significant heterogeneity or horizontal pleiotropy detected, and the results were deemed stable based on sensitivity analysis and leave-one-out test . LIMITATIONS: There are shortcomings such as data limitations, population bias, potential pleiotropy, and stratified analysis. CONCLUSIONS: While there is potential causal relationship between FGP and BD or schizophrenia, it does not exhibit any correction with OCD, depression (broad), major depression, anxiety disorders and PTSD among European populations.

Candidatus Midichloria mitochondrii can be vertically transmitted in Hyalomma anatolicum.

In this study, a tick intracellular symbiont, Candidatus Midichloria mitochondrii, was detected in Hyalomma anatolicum from Xinjiang, China. Morphological identification and cytochrome oxidase subunit I sequence alignment were used for molecular identification of the tick species. PCR detection further revealed the presence of endosymbiont C. M. mitochondrii in the tick. Specific primers were designed for Groel and 16S rRNA genes of C. M. mitochondrii for PCR amplification and phylogenetic analysis. To further investigate the vertical transmission characteristics of C. M. mitochondrii, specific primers were designed based on the FabⅠ gene fragment to detect C. M. mitochondrii in different developmental stages and organs of the tick using qPCR. Of the 336 tick specimens collected from the field, 266 samples were identified as H. anatolicum on the basis of morphological characteristics. The gene fragment alignment results of COI confirmed that these ticks were H. anatolicum. The phylogenetic analysis showed that Groel gene of C. M. mitochondrii clustered with Midichloria strains detected in Ixodes ricinus ticks from Italy and Ixodes holocyclus ticks from Australia, with 100% sequence similarity. Furthermore, the 16S rRNA gene of C. M. mitochondrii clusters with the strains isolated from Hyalomma rufipes ticks in Italy, exhibiting the highest degree of homology. qPCR results showed that C. M. mitochondrii was present at all developmental stages of H. anatolicum, with the highest relative abundance in eggs, and lower relative abundance in nymphs and unfed males. With female tick blood feeding, the relative abundance of C. M. mitochondrii increased, and a particularly high relative abundance was detected in the ovaries of engorged female ticks. This study provides information for studying the survival adaptability of H. anatolicum, and provides data for further investigation of the mechanisms regulating tick endosymbionts in ticks, enriching the reference materials for comprehensive prevention and control of tick-borne diseases.

Plant and Animal Fat Intake and Overall and Cardiovascular Disease Mortality.

Importance: The impact of dietary fat intake on long-term human health has attracted substantial research interest, and the health effects of diverse dietary fats depend on available food sources. Yet there is a paucity of data elucidating the links between dietary fats from specific food sources and health. Objective: To study associations of dietary plant and animal fat intake with overall mortality and cardiovascular disease (CVD) mortality. Design, Setting, and Participants: This large prospective cohort study took place in the US from 1995 to 2019. The analysis of men and women was conducted in the National Institutes of Health-AARP Diet and Health Study. Data were analyzed from February 2021 to May 2024. Exposures: Specific food sources of dietary fats and other dietary information were collected at baseline, using a validated food frequency questionnaire. Main Outcomes and Measures: Hazard ratios (HRs) and 24-year adjusted absolute risk differences (ARDs) were estimated using multivariable-adjusted Cox proportional hazards regression. Results: The analysis included 407 531 men and women (231 881 [56.9%] male; the mean [SD] age of the cohort was 61.2 [5.4] years). During 8 107 711 person-years of follow-up, 185 111 deaths were ascertained, including 58 526 CVD deaths. After multivariable adjustment (including adjustment for the relevant food sources), a greater intake of plant fat (HRs, 0.91 and 0.86; adjusted ARDs, -1.10% and -0.73%; P for trend < .001), particularly fat from grains (HRs, 0.92 and 0.86; adjusted ARDs, -0.98% and -0.71%; P for trend < .001) and vegetable oils (HRs, 0.88 and 0.85; adjusted ARDs, -1.40% and -0.71%; P for trend < .001), was associated with a lower risk for overall and CVD mortality, respectively, comparing the highest to the lowest quintile. In contrast, a higher intake of total animal fat (HRs, 1.16 and 1.14; adjusted ARDs, 0.78% and 0.32%; P for trend < .001), dairy fat (HRs, 1.09 and 1.07; adjusted ARDs, 0.86% and 0.24%; P for trend < .001), or egg fat (HRs, 1.13 and 1.16; adjusted ARDs, 1.40% and 0.82%; P for trend < .001) was associated with an increased risk for mortality for overall and CVD mortality, respectively, comparing the highest to the lowest quintile. Replacement of 5% energy from animal fat with 5% energy from plant fat, particularly fat from grains or vegetable oils, was associated with a lower risk for mortality: 4% to 24% reduction in overall mortality, and 5% to 30% reduction in CVD mortality. Conclusions and Relevance: The findings from this prospective cohort study demonstrated consistent but small inverse associations between a higher intake of plant fat, particularly fat from grains and vegetable oils, and a lower risk for both overall and CVD mortality. A diet with a high intake of animal-based fat, including fat from dairy foods and eggs, was also shown to be associated with an elevated risk for both overall and CVD mortality.

Role of subjective well-being and resilience in the relationship between hopelessness and suicidal ideation among older adults with moderate to severe ADL limitations in Chinese nursing homes.

PURPOSE: Hopelessness is a risk factor for suicidal ideation, whereas subjective well-being and resilience are protective factors. Nevertheless, the complicated mechanism underlying these factors has not been fully investigated among older people with moderate to severe ADL limitations in nursing homes. This cross-sectional study investigated the potential role of resilience in mediating the relationship between hopelessness and suicidal ideation as well as whether subjective well-being can moderate this mediating effect. METHODS: Older individuals (N = 332; aged ≥ 65 years; 158 males, 174 females) with moderate to severe ADL limitations from 10 nursing homes in Chongqing, China, completed this cross-sectional study from July to December 2022. Hopelessness, resilience, subjective well-being and suicidal ideation were measured. The mediating and moderating effects were explored via regression analysis with bootstrap methods. RESULTS: A total of 32.8 % (109/332) of the participants reported current suicidal ideation. The relationship between suicidal ideation and hopelessness was partly influenced by resilience (indirect effect = 0.13, 95 % CI = 0.07∼.20). Subjective well-being moderated the impact of resilience on suicidal ideation (moderating effect = 0.01, 95 % CI = 0.00∼.01) and indirectly impacted the effect of hopelessness on suicidal ideation. CONCLUSION: These results emphasize the importance of resilience and subjective well-being in mitigating suicidal ideation, which is a prevalent issue among older adults residing in nursing homes with moderate to severe ADL limitations in China.

Yellow Sticky Cards Reduce the Numbers of Trichogramma dendrolimi (Hymenoptera: Trichogrammatidae) Following Augmentative Releases against the Fruit Borers Carposina sasakii (Lepidoptera: Carposinidae) and Grapholita molesta (Lepidoptera: Tortricidae) in a Pear Orchard.

Integrated pest management relies upon mutual compatibility among pest control tactics. The fruit-boring moths Carposina sasakii and Grapholita molesta can be devastating pests of pome and stone fruit production. Trichogramma dendrolimi parasitizes the eggs of these pests, preventing their eclosion, but its efficacy can be reduced by other pest control tactics. We tested T. dendrolimi attraction to five colors, and moth attraction to six colors, in laboratory choice tests, and thereafter deployed yellow sticky cards in tandem with releases of T. dendrolimi in field trials in a pear orchard. Yellow sticky cards deployed at high density trapped T. dendrolimi and reduced their numbers post-release. They also trapped adult G. molesta, which appeared to compensate for reduced egg parasitism on this species, but not on C. sasakii, which had higher abundance in plots with yellow sticky cards. The cards also captured adult lacewings, likely reducing their numbers in the field, but did not capture large numbers of lady beetles. The results suggest that yellow sticky cards can be used at high density to control aphids, psyllids and leafhoppers in early spring (March and April) when natural enemies are in low numbers, then removed in May so as not to interfere with augmentative releases of T. dendrolimi that must be timed to coincide with peak flights of fruit-boring moths. This strategy should enhance the compatibility of yellow sticky cards with egg parasitoid releases.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-ß1 (TGF-ß1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.

A bibliometric analysis on laparoscopic pelvic floor surgery from 1996-2022.

INTRODUCTION: Pelvic organ prolapse is a common condition in middle-aged and older women. Laparoscopic pelvic floor surgery is frequently researched as a treatment for this issue. However, the effectiveness of this procedure has only been the subject of a few studies. METHODS: To quantitatively evaluate and display the relevant literature from the Web of Science database, we set the publication period of the literature from 1996 to 2022 and used VOSviewer and CiteSpace for visual analysis. RESULTS: Laparoscopic pelvic floor surgery research has increased year-on-year, with 1003 publications identified from 63 countries and published in 210 journals. In the global ranking of studies, the United States was the leader (n = 306; 30.5 %), with the most published authors being Campagna, Giuseppe (n = 17) and Scambia, Giovanni (n = 17). The International urogynecology journal included the most significant articles (n = 173; 17.2 %). Keyword analysis suggests that complications, rectal prolapse, native tissue repair, and warranty may have become hotspots in recent years. CONCLUSIONS: This bibliometric study shows that the depth and breadth of research on pelvic floor laparoscopic surgery have expanded rapidly over the last twenty-five years and that laparoscopic surgery has been recognized by different scholars or countries as an essential modality for the treatment of pelvic floor organ prolapse.

Molecular Detection of Theileria ovis, Anaplasma ovis, and Rickettsia spp. in Rhipicephalus turanicus and Hyalomma anatolicum Collected from Sheep in Southern Xinjiang, China.

The Xinjiang Uygur Autonomous Region (Xinjiang) borders eight countries and has a complex geographic environment. There are almost 45.696 million herded sheep in Xinjiang, which occupies 13.80% of China's sheep farming industry. However, there is a scarcity of reports investigating the role of sheep or ticks in Xinjiang in transmitting tick-borne diseases (TBDs). A total of 894 ticks (298 tick pools) were collected from sheep in southern Xinjiang. Out of the 298 tick pools investigated in this study, Rhipicephalus turanicus (Rh. turanicus) and Hyalomma anatolicum (H. anatolicum) were identified through morphological and molecular sequencing. In the southern part of Xinjiang, 142 (47.65%), 86 (28.86%), and 60 (20.13%) tick pools were positive for Rickettsia spp., Theileria spp., and Anaplasma spp., respectively. Interestingly, the infection rate of Rickettsia spp. (73%, 35.10%, and 28.56-41.64%) was higher in Rh. turanicus pools than in H. anatolicum pools (4%, 4.44%, and 0.10-8.79%) in this study. Fifty-one tick pools were found to harbor two pathogens, while nineteen tick pools were detected to have the three pathogens. Our findings indicate the presence of Rickettsia spp., Theileria spp., and Anaplasma spp. potentially transmitted by H. anatolicum and Rh. turanicus in sheep in southern Xinjiang, China.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

PRF1 as a prognostic gene for lymphatic metastasis in skin melanoma.

BACKGROUND: Melanoma is a highly aggressive tumor, predominantly found in the skin, recognized as skin cutaneous melanoma (SKCM). Lymph node metastasis is commonly used as the route of metastasis in SKCM, necessitating the discovery of prognostic genes associated with this process for improved prognosis. METHODS: The prognostic significance of lymph node metastasis in SKCM was assessed through Kaplan-Meier analysis in SEER and TCGA-SKCM datasets. Prognostic genes were identified and a prognostic risk model was constructed Enrichment analysis and immune cell infiltration analysis were also carried out.Moreover, a validation in vitro and in vivo were conducted by CCK8,flow cytometry, transwell and animal study. RESULTS: The Kaplan-Meier survival curve revealed that patients with lymph node metastasis had a worse prognosis compared to those without. FCGR3B and PRF1 were screened by TCGA analysis.Additionally, significant differences in nine immune cell types were observed between the two risk groups. Notably, a strong positive association with CD8 T cells and a negative relationship with M2 macrophages were exhibited by PRF1. The validation of our nomogram were conducted in vitro and in vivo, and the results showed the correlations between CD8+ T cell and PRF1. CONCLUSION: In summary, two prognostic genes (FCGR3B and PRF1) were identified, and a prognostic risk model was developed for SKCM. These findings provide a novel approach for the diagnosis and treatment of SKCM.

A solid acid derived from fishbone catalyzes the hydrolysis of cellulose into nanocellulose.

The necessity to look into waste biomass resource regeneration has increased due to growing environmental and energy-related problems. This study successfully developed an innovative fishbone-derived carbon-based solid acid catalyst using the carbonation-sulfonation method, which was subsequently applied to catalyze the hydrolysis of cellulose to produce nanocellulose. The data analysis reveals that the sulfonation treatment affects the microstructure of the catalyst, resulting in a decline in its specific surface area (134.48 m2/g decreased to 9.66 m2/g). However, this treatment doesn't hinder the introduction of acidic functional groups. In particular, the solid acid catalyst derived from fishbone exhibited a total acid content of 3.76 mmol/g, with a concentration of -SO3H groups at 0.48 mmol/g. Furthermore, the solid acids originating from fishbones manifested remarkable thermal stability, exhibiting a mass loss of <15 % at temperatures up to 600 °C. Moreover, the catalyst displayed exceptional catalytic performance during the cellulose hydrolysis reaction, achieving an optimum nanocellulose yield of 45.7 % at an optimized reaction condition. An additional noteworthy feature is the solid acid catalyst's impressive recyclability, maintaining a nanocellulose yield of 44.87 % even after undergoing five consecutive usage cycles. This research outcome underscores an innovative approach to for the sustainable utilization of waste biomass resources.

A Fe2O3/CNx cascade nanoreactor with dual-enzyme-mimetic activities for cancer hypoxia relief to amplify chemo/photodynamic therapy.

Reactive oxygen species (ROS)-mediated therapeutic strategies, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H2O2 in tumors into O2 required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe Fe2O3/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert Fe2O3 to Fe2+. After modified by MgO2 and photosensitizer Ce6, MgO2-Fe2O3/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H2O2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14 %. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells.