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Abstract Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2− locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2− endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.)

Abstract This study (NCT04728035) aimed to explore the safety and efficacy of liposomal irinotecan (HE072) in patients with metastatic triple-negative breast cancer (mTNBC). This study consisted of two parts. In part 1, the 3 + 3 design was used to investigate three dose levels of HE072 (50, 70 and 90 mg/m2). In part 2, patients were enrolled in two cohorts (mTNBC and HER2-negative breast cancer brain metastasis [BCBM]), and received HE072 70 mg/m2 every two weeks (Q2W). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and treatment emergent adverse events (TEAEs). The secondary endpoints were pharmacokinetic profiles and efficacy including objective response rate (ORR) and disease control rate (DCR) (all patients) and Central Nervous System ORR and clinical benefit rate (CBR, for patients with HER2-negative BCBM), duration of response, progression free survival (PFS), overall survival (OS). A total of 119 patients were enrolled, including 101 mTNBC and 18 HER2-negative BCBM. One dose limiting toxicity (grade 3 nausea and vomiting) occurred at 70 mg/m2, and the MTD was not reached. The most common ≥ grade 3 TEAEs related to HE072 included neutropenia (21.0%), leukopenia (18.5%), diarrhea (10.1%). Among 87 evaluable patients with mTNBC, 22 patients (25.3%) achieved overall response. The DCR was 67.8% (59/87). The median PFS and OS were 4.8 months and 14.1 months, respectively. The RP2D was 70 mg/m2 Q2W. Promising antitumor activity in heavily pre-treated patients with mTNBC was observed, which warrants further validation.

“Lives or livelihoods” is a hard trade-off when confronting COVID-19, especially for cities in the Global South. Countermeasures to protect people's lives may exert negative impacts on urban households and test their livelihood resilience. Did COVID-19 discriminate? Did livelihood resilience vary among different urban households within and across different countries and cities? Established studies focused on rural households' livelihood resilience under climate change or natural hazard based on single country context. Little is known about the variety of urban households' livelihood resilience under COVID-19 across countries and cities. This study aims to fill this gap by revealing heterogeneity of livelihood resilience at both individual urban household level and country level. First-hand questionnaire survey data (N ​= ​4374) were collected from seven cities from Bangladesh, China, India, and Philippines. Using a combination of quantitative and qualitative analytical methods, it's found that: COVID-19 did discriminate. Urban households with larger household size, no home ownership, no financial assets, and household heads with low education level, informal employed and no flexibility to transfer to work from home, were vulnerable groups. COVID-19 also discriminated across cities. Cities with a high ratio of informal workers, no effective economic relief policies and long stringent mobility restriction measures performed worse.

Phase transition at the initial solidification stage notably affects subsequent phase structure of peritectic alloys, however, detailed dynamics between entangled three-phase region remains ambiguous in the far-from-equilibrium condition during laser additive manufacturing. Here, in-situ peritectic phase transition during single-layer laser printing of an exemplary 304L stainless steel is directly investigated and quantified at high temporospatial resolution by high-speed synchrotron X-ray diffraction and imaging. These quantitative observations clarify the mechanism of coupled peritectic growth and local remelting at three-phase region. The results revealed provide in-depth understanding of phase transformation dynamics and delicate design of phase structure for metal additive manufacturing.

Most studies on the human gut microbiome have focused on the bacterial fraction rather than fungal biomics, which as resulted in an incomplete understanding of the fungal microbiome. Recent advances in microbiota detection and next-generation sequencing technology have boosted an increase in research on fungi. Symbiotic fungi have become increasingly influential in health and disease and modulate various physiologic functions within the host. Fungal infections can result in high morbidity and mortality rates and are life-threatening in some immunocompromised patients. In addition to bacterial dysbiosis, alterations in fungal communities are important and have been linked to many diseases, including asthma, mental illness, and various cancers. When investigating cancer it is imperative to consider the role of fungi alongside viruses and bacteria. This review examined the impact of intestinal fungi and peri-tumor fungi on tumorigenesis, cancer progression, and response to anticancer therapies. The review highlights the specific involvement of some fungal species in cancers include digestive tract tumors such as colorectal, pancreatic, liver, and gastric cancers, as well as non-digestive tract tumors such as lung, melanoma, breast, and ovarian cancers. Furthermore, fungal mechanisms of action, including fungus-host recognition and immune regulation, biofilm formation, toxin and metabolite production in the tumor microenvironment, and the complex effects of fungus-bacteria interactions on tumorigenesis and development, highlight the significance of potential biomarkers in cancer diagnosis and treatment.

Abstract The impact of carbon emission and other pollution generated by the construction industry on the natural environment and ecosystems is immeasurable. Wood, as a renewable building material with excellent performance, is a practical solution for future low-carbon buildings. Current screwed wood connections have good ductility, but the initial stiffness is relatively low. In this paper, composite wood connections with screw and adhesive were proposed and investigated. Static loading tests were conducted to screwed connections and composite connection specimens. The failure modes of different connection types, as well as the effects of adhesive type and adhesive connection area on the joint bearing capacity are discussed. The results show that the yield load and ultimate load of the composite joint made with the existing adhesive increased by up to 169% and 222%, respectively, compared with the screw connection. At the same time, the influence of curing time and bonding should also be taken into consideration. This study provides a foundation for wood joint design and promotes the sustainable development of the building industry.

Abstract Cancer has emerged as a formidable challenge in the 21st century, impacting society, public health, and the economy. Conventional cancer treatments often exhibit limited efficacy and considerable side effects, particularly in managing the advanced stages of the disease. Photodynamic therapy (PDT), a contemporary non-invasive therapeutic approach, employs photosensitizers (PS) in conjunction with precise light wavelengths to selectively target diseased tissues, inducing the generation of reactive oxygen species and ultimately leading to cancer cell apoptosis. In contrast to conventional therapies, PDT presents a lower incidence of side effects and greater precision in targeting. The integration of intelligent nanotechnology into PDT has markedly improved its effectiveness, as evidenced by the remarkable synergistic antitumor effects observed with the utilization of multifunctional nanoplatforms in conjunction with PDT. This paper provides a concise overview of the principles underlying PS and PDT, while also delving into the utilization of nanomaterial-based PDT in the context of cancer treatment.

Abstract Purpose County-level hospitals in China constitute a vital component of the healthcare system, delivering essential medical services, emergency care, and specialized treatments, particularly in oncology. This study aimed to comprehensively evaluate the current status of cancer diagnosis and treatment in county hospitals and assess their overall capacity. Methods A nationwide cross-sectional survey by the China Anti-cancer Association (CACA) from February to May 2023 assessed cancer diagnosis and treatment in mainland China's county hospitals. Using a multi-center approach, a fifty-five-question questionnaire was administered to oncology professionals and management staffs, focusing on hospital facilities, oncology specialists, cancer cases, treatment capabilities, and healthcare collaboration. Questionnaire reliability and validity were established in a 2022 national survey. Participants, aged 18 or older, were recruited through purposive sampling, receiving self-administered questionnaires for confidentiality. SAS 9.4 software facilitated statistical analysis. Results The study encompassed 76 county-level medical institutions, with 82.9% of them featuring established oncology departments providing comprehensive cancer care, including early screening, diagnosis, treatment, and long-term follow-up. Notably, a total of 56.6% of the institutions surveyed implemented programs for cancer screening and early diagnosis. A significant proportion of advanced cancer patients received treatment and follow-up at the county level. Persistent disparities in medical insurance policies at the county level were identified as a continuing challenge. Furthermore, 82.9% of hospitals had cultivated collaborative relationships with higher-level institutions to enhance patient care quality and treatment capacity. The study revealed a 56.6% shortage of remote collaboration platforms in these hospitals. The need for a patient-centered approach in county hospitals was underscored. Conclusion While county-level hospitals face challenges, such as a shortage of specialized oncologists and advanced resources, they exhibit progress in standardizing cancer care to enhance diagnosis and treatment in rural areas.

Abstract Using acrylic acid advanced ester and styrene as raw materials, the long-chain polyester polymer, polyacrylic acid advanced ester-styrene pour point depressant (P-PPD), was synthesized by molecular design, and its structure was characterized by infrared spectroscopy and nuclear magnetic resonance. In addition, this study experimentally investigated the effect of P-PPD on the phase equilibrium and induction time of natural gas hydrate inhibitors in deionized water (DW) and crude oil/water (O/W) systems, respectively. Polyvinylpyrrolidone (PVP) and mono ethylene glycol (EG) were selected as representatives of kinetic hydrate inhibitor (KHIs) and thermodynamic hydrate inhibitor (THIs), respectively. The results exhibit that P-PPD played a sight role in the phase equilibrium of hydrate, while the addition of P-PPD significantly prolonged the induction time of methane hydrate both in O/W + PVP, OW + EG and O/W + PVP + EG system, indicating that the addition of as-synthesized PPD has a synergistic inhibition effect on the nucleation ability of methane hydrate and can prevent hydrate from formatting during oil and gas transport process, and thus guarantee the flow assurance. The findings of this work will provide a data reference for the hybrid use of hydrate inhibitors and pour point depressants in oil and gas transport.

Abstract As unmanned vehicle technology advances rapidly, obstacle recognition and target detection are crucial links, which directly affect the driving safety and efficiency of unmanned vehicles. In response to the inaccurate localization of small targets such as pedestrians in current object detection tasks and the problem of losing local features in the PointPillars, this paper proposes a three-dimensional object detection method based on improved PointPillars. Firstly, addressing the issue of lost spatial and local information in the PointPillars, the feature encoding part of the PointPillars is improved, and a new pillar feature enhancement extraction module, CSM-Module, is proposed. Channel encoding and spatial encoding are introduced in the new pillar feature enhancement extraction module, fully considering the spatial information and local detailed geometric information of each pillar, thereby enhancing the feature representation capability of each pillar. Secondly, based on the fusion of CSPDarknet and SENet, a new backbone network CSE-Net is designed in this paper, enabling the extraction of rich contextual semantic information and multi-scale global features, thereby enhancing the feature extraction capability. Our method achieves higher detection accuracy when validated on the KITTI dataset. Compared to the original network, the improved algorithm’s average detection accuracy is increased by 3.42%, it shows that the method is reasonable and valuable.

Abstract Conventional welding methods encounter significant challenges, including poor weldability, low joint strength, and the formation of brittle intermetallic compounds, primarily due to the substantial disparities in the physical and chemical properties of aluminum and iron. To mitigate these issues, the vaporizing foil actuator welding (VFAW) process has emerged as a highly promising solid-phase welding technology, particularly suitable for joining dissimilar metals with pronounced differences in properties, such as aluminum alloys and stainless steels. The present study provides an innovative quantitative analysis of the interfacial impact energy conversion mechanisms within the VFAW process. The analysis reveals that the energy responsible for accelerating the flyer workpiece comprises burst vaporization energy ( $$E_d$$ E d ) and continuous vaporization energy ( $$E_p$$ E p ), with $$E_d$$ E d identified as the primary energy source, contributing approximately 65–80% of the total energy required for acceleration. Further examination elucidates the mechanisms underlying heat generation and transfer during the interface collision. The investigation identifies the formation of an overheating zone at the interface, attributed to the combined effects of plastic deformation energy and adiabatic shear energy within the flyer workpiece. Consequently, the interface temperature can rise significantly, reaching up to 1394 K, with impact velocities as high as 925 m/s. The analyses contribute to establishing a theoretical foundation for understanding the interface bonding mechanisms characteristic of the vaporizing foil actuator welding method.

Abstract Aiming at the problem that the mobility characteristics of electric vehicles (EVs) lead to the complexity of optimal scheduling among multiple decision‐making subjects, the authors propose a multi‐microgrid bi‐layer economic scheduling strategy considering evolutionary‐stackelberg hybrid game of EVs. Firstly, in order to accurately analyse the influence of interaction among EVs, an electric vehicle aggregator (EVA) selection strategy for EV users based on evolutionary game among microgrids and a reconciliation strategy of EVA service fee are established. Secondly, a two‐layer economic scheduling strategy for microgrids is proposed based on the Stackelberg game. The microgrid operator, as a leader, sets the internal price of microgrid based on the supply‐demand balance; aggregators, as followers, adjust their electricity consumption and EVA choices based on the internal price and the evolutionary game model. Then, a multi‐microgrid electricity‐sharing trading strategy is constructed using the supply‐demand ratio to encourage sub‐microgrids to participate in internal transactions. Finally, the case shows that the proposed strategy can optimise the distribution of EVs among microgrids. Combining the across‐time‐and‐space energy transmission potential of EVs and the flexible complementary capability of multi‐microgrid, it can improve the operating economy of each microgrid.

Abstract Background Screen exposure, particularly recreational screen exposure, is an integral part of children’s lives. However, little is known about how family factors influence children’s excessive screen exposure, especially in the context of 69 million left-behind children experiencing parent–child separation in China. This study mainly concentrates on the correlation between parental migration, type of caregiver, depression and disciplinary practices of the caregiver and children’s screen exposure, including average daily screen time (on weekdays or weekends) and screen content (recreational activities or learning activities). Methods For a cross-sectional study, we collected data of family basic features, parental migration status and children’s screen use in the past week from caregivers of 1,592 children aged 1–66 months in Anhui province. Children were classified into left-behind children (LBC), previously left-behind children (PLBC) and never left-behind children (NLBC) based on their parental migration. Multiple linear regression and binary logistic regression were used to identified the association between family factors and children’s screen exposure. Results Overall, PLBC had higher rates of screen exposure, as well as higher average daily exposure times, than NLBC and LBC. The results of logistic regression showed that PLBC had a higher likelihood of excessive screen use compared to NLBC (60 min/day, OR = 1.40, p

Abstract Background The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain. Methods We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk. Results Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37–0.91 in US NHANES; 0.51, 0.46–0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73–0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79–0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status. Conclusions Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging.

Fritillaria is a widely used traditional Chinese medicine, with a complex source and a wide variety of medicinal materials. Different varieties have similar external characteristics, making it difficult to distinguish using traditional methods. To achieve rapid and objective identification of Fritillaria species, this study proposed a method for rapid identification based on electronic tongue and electronic eye combined with a deep learning model. Electronic tongue and electronic eye were utilized to collect gustatory fingerprint and visual image information from different categories of Fritillaria, respectively. An enhanced Transformer encoder based on causal attention mechanism was employed to extract time-series features from the ET signals and augment the ability to extract local features. Meanwhile, an improved ShuffleNetV2 network based on coordinate attention mechanism was used to extract morphological features of EE image and suppress background noise. Subsequently, a feature weighted fusion module was presented to adaptively integrate the feature information extracted from both the electronic tongue and electronic eye, and achieve classification and recognition of the fused features. The experimental results indicated that the proposed information fusion method had better classification performance compared to separate usage of electronic tongue and electronic eye, with a testing accuracy of 98.4%. This study provides a novel approach for rapidly identifying Fritillaria varieties, which offers research insights into the classification and traceability analysis of other Chinese medicinal materials.

Abstract Background F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). Methods This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. Results The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. Conclusions A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Ophiocordyceps encompasses over 300 species, demonstrating a wide range of morphological features, hosts and habitats within its species diversity. In this study, two novel species in Ophiocordyceps were revealed parasitising Hepialidae larva buried in soil. Ophiocordyceps albastroma was morphologically characterised by white stromata, solitary and cylindrical conidiogenous cells and smooth ovoid or ellipsoidal conidia. Ophiocordyceps nigristroma was characterised by woody and dark brown stromata, monophialidic, swollen base and lageniform conidiogenous cells and smooth fusiform or oval conidia. The two new species formed a separate clade, respectively, based on the phylogenetic analyses of a combined dataset including nrSSU, nrLSU, rpb1, rpb2, and tef-1α, as well as a dataset of mitochondrial 14 protein coding genes (PCGs). They were all closely grouped with O. sinensis. The mitochondrial genomes of them were first reported. Their mitogenomes were all typical of circular molecules, with positive AT and GC skew, similar GC content, similar genetic composition, similar codon usage and conservative gene positions. However, the length of the mitogenomes varied. Changes in the length of the genes were the leading cause of changes in the length of mitochondrial genome of Ophiocordyceps. The discovery and identification of new Ophiocordyceps species and analysis their mitochondrial genomes may serve as foundations for phylogeny and diversity research within the genus Ophiocordyceps.

Abstract Ultrasonic processing of solidifying metals in additive manufacturing can provide grain refinement and advantageous mechanical properties. However, the specific physical mechanisms of microstructural refinement relevant to laser-based additive manufacturing have not been directly observed because of sub-millimeter length scales and rapid solidification rates associated with melt pools. Here, high-speed synchrotron X-ray imaging is used to observe the effect of ultrasonic vibration directly on melt pool dynamics and solidification of Al6061 alloy. The high temporal and spatial resolution enabled direct observation of cavitation effects driven by a 20.2 kHz ultrasonic source. We utilized multiphysics simulations to validate the postulated connection between ultrasonic treatment and solidification. The X-ray results show a decrease in melt pool and keyhole depth fluctuations during melting and promotion of pore migration toward the melt pool surface with applied sonication. Additionally, the simulation results reveal increased localized melt pool flow velocity, cooling rates, and thermal gradients with applied sonication. This work shows how ultrasonic treatment can impact melt pools and its potential for improving part quality.

Abstract Genetic epilepsy with febrile seizures plus (GEFS+) is a genetic epilepsy syndrome characterized by a marked hereditary tendency inherited as an autosomal dominant trait. Patients with GEFS+ may develop typical febrile seizures (FS), while generalized tonic–clonic seizures (GTCSs) with fever commonly occur between 3 months and 6 years of age, which is generally followed by febrile seizure plus (FS+), with or without absence seizures, focal seizures, or GTCSs. GEFS+ exhibits significant genetic heterogeneity, with polymerase chain reaction, exon sequencing, and single nucleotide polymorphism analyses all showing that the occurrence of GEFS+ is mainly related to mutations in the gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2) gene. The most common mutations in GABRG2 are separated in large autosomal dominant families, but their pathogenesis remains unclear. The predominant types of GABRG2 mutations include missense (c.983A → T, c.245G → A, p.Met199Val), nonsense (R136*, Q390*, W429*), frameshift (c.1329delC, p.Val462fs*33, p.Pro59fs*12), point (P83S), and splice site (IVS6+2T → G) mutations. All of these mutations types can reduce the function of ion channels on the cell membrane; however, the degree and mechanism underlying these dysfunctions are different and could be linked to the main mechanism of epilepsy. The γ2 subunit plays a special role in receptor trafficking and is closely related to its structural specificity. This review focused on investigating the relationship between GEFS+ and GABRG2 mutation types in recent years, discussing novel aspects deemed to be great significance for clinically accurate diagnosis, anti-epileptic treatment strategies, and new drug development.

BackgroundPostherpetic neuralgia (PHN) is a chronic neuropathic pain condition in elderly patients following herpes zoster infection. Conventional treatments often have inconsistent efficacy and significant side effects. Combining spinal cord stimulation (SCS) with lidocaine patches may enhance pain relief by targeting central and peripheral pain mechanisms.MethodsThis randomized, controlled, single-blind trial enrolled 97 patients aged ≥60 years with PHN lasting ≥6 months. Participants were assigned to SCS with a 5% lidocaine patch (n = 49) or SCS with a placebo patch (n = 48). Both groups received oral pregabalin. The placebo patch was identical in appearance to ensure blinding. Pain intensity (VAS) and sleep quality (PSQI) were assessed at baseline and on days 1, 3, 7, 30, and 90 post-interventions. Subgroup analyses by age and PHN duration were conducted.ResultsAt day 90, the experimental group had greater reductions in VAS scores (1.6 ± 1.1) than the control group (2.7 ± 1.3, p

Objective: This study aimed to assess the sensitivity and specificity of magnifying endoscopy in the examination of patients with high-risk factors for cervical lesions. Methods: Two equally skilled colposcopy specialists examined 59 patients admitted to the Obstetrics and Gynecology Hospital of Fudan University between March 14, 2023, and April 15, 2023. These patients underwent both colposcopy and magnifying endoscopy examinations. Preliminary diagnoses were then made by the two colposcopy specialists using colposcopy and magnifying endoscopy. The sensitivity and specificity of these methods were then evaluated compared to the postoperative pathology diagnosis for a better understanding of their efficacy. Results: Colposcopy exhibited sensitivity rates of 23.08 % for diagnosing normal tissue, 10 % for low-grade squamous intraepithelial lesions (LSIL), 90 % for high-grade squamous intraepithelial lesions (HSIL), and 84.62 % for cervical cancer, with specificity rates of 93.94 %, 67.35 %, 71.43 %, and 100 %, respectively. In contrast, magnifying endoscopy demonstrated sensitivity rates of 42.31 %, 40 %, 90 %, and 92.31 % for normal tissue, LSIL, HSIL, and cervical cancer, respectively. The corresponding specificity rates for these categories were 87.88 %, 77.55 %, 83.67 %, and 100 %. Conclusion: Magnifying endoscopy exhibits higher sensitivity and specificity compared to colposcopy in detecting cervical lesions. With the ability to magnify lesions up to 520 times, magnifying endoscopy facilitates precise visualization of cellular-level lesions, as well as associated anatomical features and vascular signals.

IntroductionMitochondria are essential organelles that provide energy for plants. They are semi-autonomous, maternally inherited, and closely linked to cytoplasmic male sterility (CMS) in plants. Lonicera macranthoides, a widely used medicinal plant from the Caprifoliaceae family, is rich in chlorogenic acid (CGA) and its analogues, which are known for their antiviral and anticancer properties. However, studies on the mitogenome of L. macranthoides still remain limited.MethodsThe mitochondrial DNA contained in the whole genome DNA was extracted from a male sterile cultivar of L. macranthoides, named ‘Yulei 1’. Next-generation sequencing (NGS) and third-generation sequencing (TGS) technologies were combined to obtain the mitogenome. RNA editing events were identified by integrating the mitogenome data with RNA sequencing data from leaf, stem, and flower tissues. The potential causes of male sterility in ‘Yulei 1’ were analyzed based on the loss of functional genes, mitogenome rearrangements, RNA editing events, and open reading frames (ORFs).Results and discussionThe complete mitogenome of L. macranthoides ‘Yulei 1’ was obtained for the first time, with a length of 1,002,202 bp. It contains 48 protein-coding genes (PCGs), 26 tRNA genes, and 3 rRNA genes. Additionally, 79 simple sequence repeats (SSRs), 39 tandem repeats, and 99 dispersed repeats were identified. Among these, two direct repeats (RP1a/1b, RP2a/2b) and two inverse repeats (RP3a/b, RP4a/b) may facilitate mitogenome recombination. Gene transfer analysis revealed that 4.36% and 21.98% of mitogenomic sequences mapped to the chloroplast and nuclear genomes, respectively. Phylogenetic analysis indicated that L. macranthoides is closest to L. japonica at the mitogenome level. Notably, RNA editing events varied across different plant tissues, with 357 editing sites in 30 PCGs in leaves, 138 sites in 24 PCGs in flowers, and 68 sites in 13 PCGs in stems. Finally, all indications of CMS in the mitogenome were screened, including the detection of ORFs, and the findings showed no mutations in the mitogenome that would explain the sterility of ‘Yulei 1’. Overall, our study provides a complete mitogenome of L. macranthoides, which will aid in its genetic marker exploration, evolutionary relationship analysis, and breeding programs.

Abstract The expansion of neural progenitors and production of distinct neurons are crucial for architectural assembly and formation of connectivity in human brains. Subplate neurons (SPNs) are among the firstborn neurons in the human fetal cerebral cortex, and play a critical role in establishing intra‐ and extracortical connections. However, little is known about SPN origin and developmental lineages. In this study, spatial landscapes and molecular trajectories of SPNs in the human fetal cortices from gestational weeks (GW) 10 to 25 are created by performing spatial transcriptomics and single‐cell RNA sequencing. Genes known to be evolutionarily human‐specific and genes associated with extracellular matrices (ECMs) are found to maintain stable proportions of subplate neurons among other neuronal types. Enriched ECM gene expression in SPNs varies in distinct cortical regions, with the highest level in the frontal lobe of human fetal brains. This study reveals molecular origin and lineage specification of subplate neurons in the human fetal cerebral cortices, and highlights underpinnings of SPNs to cortical neurogenesis and early structural folding.

Abstract The goal of the next‐generation COVID‐19 vaccine is to provide rapid respiratory tract protection with a single dose. Circulating antibodies do not protect the olfactory mucosa from viral infection, necessitating localized mucosal immunization. Live attenuated vesicular stomatitis virus (VSVMT)‐based COVID‐19 vaccines effectively stimulate mucosal immunity in animals, though safety concerns remain, particularly in immunocompromised populations. A viral vector capable of single‐cycle replication may face less stringent regulatory requirements. A replication‐defective VSVMT is developed with its G protein replaced by a SARS‐CoV‐2 spike protein (S) mutant, where residues K986 and V987 are substituted by prolines (S2P). This studies show that single‐cycle VSVMT encoding Omicron subvariant S2P (VSVMT‐S2P) is safe in both healthy and immunocompromised animals treated with cyclophosphamide (CP). Significant antibody and T‐cell responses against the spike protein are observed in VSVMT‐S2P vaccinated healthy animals. Intramuscular VSVMT‐S2P administration induces neutralizing antibody responses comparable to those from replication‐competent VSVMT‐S. In immunocompromised animals, lower and delayed immune responses are observed. Thus, single‐cycle M‐protein mutated VSV offers a safe and effective platform for SARS‐CoV‐2 immunogen delivery. Remarkably, replication‐competent VSVMT‐S caused no pathogenicity and elicited potent mucosal immunity via intranasal administration, highlighting its potential as a mucosal COVID‐19 vaccine.

In our previous study, three TaPSK genes highly expressed in the roots of wheat were screened. To explore the effects of adverse stresses on the wheat root phenotype and the expression of TaPSK3, TaPSK9 and TaPSK10, we measured the phenotypic parameters of the JM22 root system at the seedling stage after treatment with different concentrations of NaCl and PEG6000. Additionally, the relative expression levels of TaPSK3, TaPSK9, and TaPSK10 were analyzed via RT-qPCR within 72 h of treatment with 150 mM NaCl and 30% PEG6000. The results revealed that drought and salt stress significantly inhibited phenotypic parameters such as total root length, root surface area, root biomass distribution estimation and root tip number in wheat. Notably, salt stress causes wheat roots to germinate more root hairs. The expression of TaPSK3 did not change significantly during salt stress but was upregulated approximately five-fold at 12 h of drought stress. The gene expression levels of TaPSK9 and TaPSK10 were upregulated to varying degrees but gradually returned to normal at 72 h. These results show that when wheat encounters stresses, the expression of TaPSK genes is upregulated to promote root growth and ensure the normal growth and development of plants. This study provides data and theoretical support for further study of TaPSK gene function and cultivation of high-quality wheat plants with strong stress resistance.

Objective To explore the advantages and effectiveness of preoperative 3D printing planning technology combined with orthopedic surgical robot-assisted screw placement in the minimally invasive treatment of pelvic fractures compared to orthopedic surgical robot-assisted screw placement alone. Methods A retrospective analysis of the clinical data of 29 patients with unstable pelvic fractures treated with orthopedic surgical robot-assisted percutaneous screw fixation from July 2021 to August 2023 was conducted. Among them, 13 patients who underwent preoperative 3D printing technology for screw planning were assigned to the experimental group, and the remaining 16 patients were assigned to the control group. All patients underwent screw fixation alone or combined with other fixation methods for fracture fixation. The application of preoperative 3D printing planning in orthopedic surgical robot operations was described. The intraoperative screw drawing time, invasive operation time, number of fluoroscopies during invasive operation, postoperative evaluation of screw accuracy, fracture healing, complications, and functional outcomes were recorded and compared between the two groups. Results All patients successfully underwent surgery, with one patient in the control group experiencing numbness in the sciatic nerve innervation area. All patients were followed up for 4–15 months, with an average of 8 months, and all fractures achieved healing. The experimental group had a total of 26 screws inserted, while the control group had 30 screws. In the experimental group, the intraoperative screw drawing time was 3.0 (3.0, 3.37) min, significantly shorter than 4.0 (3.6, 4.0) min in the control group (P 0.05). Conclusion In the treatment of pelvic fractures using screw fixation, preoperative 3D printing technology planning combined with orthopedic surgical robots, compared to orthopedic surgical robot-assisted screw placement alone, can significantly reduce intraoperative screw drawing time, decrease drawing difficulty, enhance screw placement accuracy, and does not increase invasive operation time or the number of fluoroscopies. This approach makes the surgery safer and is a method worth applying.

3D moment invariants are important tools for 3D image feature representation. In this paper, we introduced a novel approach for constructing 3D moment invariants using Gaussian geometric moments. Our proposed method demonstrated invariance under translation, rotation, and scale transformations. The numerical experiments validate the invariance and robustness of the proposed method, comparing it with traditional 3D geometric moments and revealing superior performance in the presence of noise and transformations. Additionally, the method is applied to content-based 3D image retrieval, exhibiting promising results through Minkowski distance-based retrieval on the Princeton Shape Benchmark (PSB) database.

Objective Despite revascularization has been proven to be the optimal choice of moyamoya disease (MMD), many complications may occur in this context.. This study aimed to analyse the risk factors for new or expanded symptomatic infarctions of patients with MMD after revascularization.Methods Patients with MMD who received revascularization in our department were retrospectively enrolled, new or expanded cerebral infarction within a month after revascularization was the main concern. Basic and clinical information, and intraoperative conditions were evaluated. Univariate and multivariate analyses were performed to evaluate the risk factors. Receiver operating characteristic curve analysis was conducted to evaluate the efficiency of the risk factors.Results Eventually, 108 consecutive patients received 174 surgeries were enrolled, experienced new or expanded infarction occured in 13 (7.47%) surgeries, which showed higher Suzuki stage on the non-operative side, more posterior cerebral artery (PCA) involvement, and more intraoperative hypotension compared to those without infarction(p

Background and purpose The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting.Methods 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan–Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index.Results A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p

Objectives: Retirement represents a significant life transition, with post-retirement status serving as a pivotal aspect of aging research. Despite its potential significance, little research has delved into the relationship between continuing work after retirement and the frailty. This study aims to investigate the association between continuing work after retirement and the incidence of frailty among older individuals. Design: A nationally representative cohort study. Setting and participants: We utilized data from 4 waves (2011, 2013, 2015 and 2018) of the China Health and Retirement Longitudinal Study and a total of 5,960 participants were included in the study after applying specific inclusion and exclusion criteria. Methods: Frailty was assessed using a Frailty Index. To balance baseline covariates between workers (n = 3,170) and non-workers (n = 2,790), we employed inverse propensity of treatment weighting. The relationship between work status and the incidence of frailty was examined using Cox proportional hazards analysis, with results reported as hazard ratios and 95% confidence intervals. Results: A total of 5,960 participants (mean age 64 years; 42.1% male) were included in the analysis. Over a mean follow-up of 6.9 years, 2,105 cases of frailty were identified. In the cohort analysis, following adjustment using the inverse propensity of treatment weighting (IPTW), continuing work after retirement showed a negative association with frailty incidence, with an HR of 0.72 (95% CI, 0.65−0.79). Subgroup analysis revealed a more significant protective effect of continuing work beyond retirement age among individuals aged 65 or older, males, smokers, and those with limited social activities. Conclusions: In summary, this study identified a significant association between continuing work after retirement and a decreased risk of frailty. The findings underscore the potential benefits of policies promoting social engagement and extending working life in enhancing the quality of life for the aging population.

BackgroundTuberculosis (TB) is a leading cause of death worldwide from a single infectious agent. In China the most common extra-pulmonary TB (EPTB) is pleural tuberculosis (PLTB). An important clinical feature of PLTB is that the lymphocytes associated with TB will accumulate in the pleural fluid. The adaptive immune repertoires play important roles in Mycobacterium tuberculosis (Mtb) infection.MethodsIn this study, 10 PLTB patients were enrolled, and their Peripheral Blood Mononuclear Cells(PBMCs) and Pleural Effusion Mononuclear Cells(PEMCs) were collected. After T cells were purified from PBMCs and PEMCs, high-throughput immunosequencing of the TCRβ chain (TRB), TCRγ chain(TRG), and B cell receptor(BCR) immunoglobulin heavy chain (IGH) were conducted on these samples.ResultsThe TRB, TRG, and BCR IGH repertoires were characterized between the pleural effusion and blood in PLTB patients, and the shared clones were analyzed and collected. The binding activity of antibodies in plasma and pleural effusion to Mtb antigens was tested which indicates that different antibodies responses to Mtb antigens in plasma and pleural effusion in PLTB patients. Moreover, GLIPH2 was used to identify the specificity groups of TRB clusters and Mtb-specific TRB sequences were analyzed and collected by VJ mapping.ConclusionWe characterize the adaptive immune repertoires and identify the shared clones and Mtb-specific clones in pleural effusion and blood in PLTB patients which can give important clues for TB diagnosis, treatment, and vaccine development.

Abstract Hydrogel‐based 3D cell cultures are extensively utilized to create biomimetic cellular microstructures. However, there is still lack of effective method for both evaluation of the complex interaction of cells with hydrogel and the functionality of the resulting micro‐structures. This limitation impedes the further application of these microstructures as microphysiological models (microPMs) for the screening of potential culture condition combinations to enhance the skeletal muscle regeneration. This paper introduces a two‐probe micromanipulation method for the large‐scale assessment of viscoelasticity and contractile force (CF) of skeletal muscle microPMs, which are produced in high‐throughput via microfluidic spinning and 96‐well culture. The collected data demonstrate that viscoelasticity parameters (E* and tanδ) and CF both measured in a solution environment are indicative of the formation of cellular structures without hydrogel residue and the subsequent generation of myotubes, respectively. This study have developed screening criterias that integrate E*, tanδ, and CF to examine the effects of multifactorial interactions on muscle fiber repair under hypoxic conditions and within bioprinted bipennate muscle structures. This approach has improved the quality of hypoxic threshold evaluation and aligned cell growth in 3D. The proposed method is useful in exploring the role of different factors in muscle tissue regeneration with limited resources.

Urban environments and cardiovascular health are closely linked, yet only a few specific exposures have been explored in isolation and mostly adopting cross-sectional design. The influence of socioeconomic status and genetic predisposition also remains unclear. Hence, leveraging the UK Biobank data (n = 206,681), we conducted a prospective analysis of 213 urban environmental variables and their association with atherosclerotic cardiovascular disease (ASCVD). The ExWAS and regularized Cox models analyses highlighted air pollution, industrial sites, and complex street networks as primary environmental risk factors. Instead, land-use density of leisure, public services, infrastructure and residential, and drinking water hardness showed a negative association with ASCVD risk. By integrating sparse canonical correlation and mediation analyses, we found distinct urban environment patterns through diverse pathways influence ASCVD. The environment characterized by pollution and complex streets impact ASCVD through adverse mental health (mediation proportion:30.7 %, 95 % CI:22.4 %-44.0 %), while highly-developed community and high-water hardness environment via cardiometabolic status (22.6 %, 95 % CI:19.7 %-26.0 %). Further, we found low socioeconomic status amplifies disadvantaged urban environment effects on ASCVD, yet there were no similar findings for ASCVD genetic predisposition. This research deepened our understanding of city-cardiovascular health links and the role of socioeconomic status, with implications for urban planning and public health interventions.

Objective: The aim of this study is to investigate the predictive value of indicators associated with microcirculation, capillary refill time (CRT), perfusion index (PI), and mottling score, on the prognosis of patients with septic shock. Method: A retrospective clinical study was conducted encompassing 78 patients diagnosed with septic shock and admitted to the Department of Critical Care Medicine at our hospital from January 2019 to January 2022. The study collated the clinical data of these patients, focusing on macrocirculatory hemodynamic parameters and microcirculatory indices. The parameters of interest were recorded at 0, 6, 24, and 48 h post-admission, including heart rate, mean arterial pressure (MAP), venous-to-arterial carbon dioxide partial pressure difference, superior vena cava oxygen saturation, lactic acid (LAC), CRT, PI, and mottling score. The enrolled patients were stratified into two cohorts based on the 28-day mortality rate: a survival group and a mortality group. A non-parametric statistical test was employed to compare the CRT, PI, and mottling score between the two groups. Furthermore, the predictive value of these microcirculatory indicators for mortality in septic shock patients was assessed using receiver operating characteristic (ROC) curve analysis. This methodology allowed for the evaluation of the prognostic accuracy of CRT, PI, and mottling score as indicators for mortality in the context of septic shock. Results: The vasoactive drug dose, PI, LAC, mottling score, and CRT upon admission in the survival group were significantly better than those in the mortality group at hour 6 of treatment, hour 24 of treatment, and hour 48 of treatment (P

ObjectiveTo evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) combined with repetitive peripheral magnetic stimulation (rPMS) on upper limb motor dysfunction after stroke.MethodsWe systematically searched databases up to May 2024, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang, and CBM. Randomized controlled trials (RCTs) examining the application of rTMS combined rPMS on upper limb motor dysfunction after stroke were included based on predefined inclusion criteria. We used Cochrane Risk of Bias 2 tool to assess bias risk of the included RCTs. Meta-analysis was conducted using RevMan 5.4 and Stata 17.0 software.ResultsA total of 9 RCTs involving 483 participants were included in this study. Compared with the control groups that used either conventional therapy or rTMS alone, the experimental group that used rTMS combined rPMS showed significant improvements in stroke patients' upper limb motor function [MD = 3.65, 95% CI (2.75, 4.54), P < 0.05], ability of daily living [MD = 4.50, 95% CI (3.50, 5.50), P < 0.05], and spasticity [MD = –0.34, 95% CI (−0.48, −0.20), P < 0.05]. Meanwhile, in terms of neurophysiological indicators, significant differences were found both for motor evoked potential latency [MD = −1.77, 95% CI (−3.19, −0.35), P < 0.05] and motor evoked potential amplitude [MD = 0.25, 95% CI (0.01, 0.49), P < 0.05].ConclusionThis study provides low-level evidence that the therapy of LF-rTMS or HF-rTMS combined with rPMS can improve the upper limb motor function and daily living ability of stroke patients. However, given that the low quality of the evidence for the evaluation results, further evidence from high-quality studies is needed to substantiate this conclusion.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024539195, PROSPERO Platform [CRD42024539195].

ObjectivesThe aim of this study is to develop an ultrasound-based fusion model of clinical, radiomics and deep learning (CRDL) for accurate diagnosis of benign and malignant soft tissue tumors (STTs)MethodsIn this retrospective study, ultrasound images and clinical data of patients with STTs from two hospitals were collected between January 2021 and December 2023. Radiomics features and deep learning features were extracted from the ultrasound images, and the optimal features were selected to construct fusion models using support vector machines. The predictive performance of the model was evaluated based on three aspects: discrimination, calibration and clinical usefulness. The DeLong test was used to compare whether there was a significant difference in AUC between the models. Finally, two radiologists who were unaware of the clinical information performed an independent diagnosis and a model-assisted diagnosis of the tumor to compare the performance of the two diagnoses.ResultsA training cohort of 516 patients from Hospital-1 and an external validation cohort of 78 patients from Hospital-2 were included in the study. The Pre-FM CRDL showed the best performance in predicting STTs, with area under the curve (AUC) of 0.911 (95%CI: 0.894-0.928) and 0.948 (95%CI: 0.906-0.990) for training cohort and external validation cohort, respectively. The DeLong test showed that the Pre-FM CRDL significantly outperformed the clinical models (P< 0.05). In addition, the Pre-FM CRDL can improve the diagnostic accuracy of radiologists.ConclusionThis study demonstrates the high clinical applicability of the fusion model in the differential diagnosis of STTs.

Abstract Numerous plants evolve ingeniously microcantilever‐based hairs to ultra‐sensitively detect out‐of‐plane quasi‐static tactile loads, providing a natural blueprint for upgrading the industrial static mode microcantilever sensors, but how do the biological sensory hairs work mechanically? Here, the action potential‐producing trigger hairs of carnivorous Venus flytraps (Dionaea muscipula) are investigated in detail from biomechanical perspective. Under tiny mechanical stimulation, the deformable trigger hair, composed of distal stiff lever and proximal flexible podium, will lead to rapid trap closure and prey capture. The multiple features determining the sensitivity such as conical morphology, multi‐scale functional structures, kidney‐shaped sensory cells, and combined deformation under tiny mechanical stimulation are comprehensively researched. Based on materials mechanics, finite element simulation, and bio‐inspired original artificial sensors, it is verified that the omnidirectional ultra‐sensitivity of trigger hair is attributed to the stiff‐flexible coupling of material, the double stress concentration, the circular distribution of sensory cells, and the positive local buckling. Also, the balance strategy of slender hair between sensitivity and structural stability (i.e., avoiding disastrous collapse) is detailed revealed. The unique basic biomechanical mechanism underlying trigger hairs is essential for significantly enhancing the performance of the traditional industrial static mode microcantilever sensors, and ensure the stability of arbitrary load perception.

Abstract Background Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM). Methods This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed. Results In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI

Abstract T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR β sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

Abstract The main cause of corneal blindness worldwide is keratitis, especially the infectious form caused by bacteria, fungi, viruses, and Acanthamoeba. The key to effective management of infectious keratitis hinges on prompt and precise diagnosis. Nevertheless, the current gold standard, such as cultures of corneal scrapings, remains time-consuming and frequently yields false-negative results. Here, using 23,055 slit-lamp images collected from 12 clinical centers nationwide, this study constructed a clinically feasible deep learning system, DeepIK, that could emulate the diagnostic process of a human expert to identify and differentiate bacterial, fungal, viral, amebic, and noninfectious keratitis. DeepIK exhibited remarkable performance in internal, external, and prospective datasets (all areas under the receiver operating characteristic curves > 0.96) and outperformed three other state-of-the-art algorithms (DenseNet121, InceptionResNetV2, and Swin-Transformer). Our study indicates that DeepIK possesses the capability to assist ophthalmologists in accurately and swiftly identifying various infectious keratitis types from slit-lamp images, thereby facilitating timely and targeted treatment.

Abstract Objective To establish a machine learning model based on radiomics and clinical features derived from non-contrast CT to predict futile recanalization (FR) in patients with anterior circulation acute ischemic stroke (AIS) undergoing endovascular treatment. Methods A retrospective analysis was conducted on 174 patients who underwent endovascular treatment for acute anterior circulation ischemic stroke between January 2020 and December 2023. FR was defined as successful recanalization but poor prognosis at 90 days (modified Rankin Scale, mRS 4–6). Radiomic features were extracted from non-contrast CT and selected using the least absolute shrinkage and selection operator (LASSO) regression method. Logistic regression (LR) model was used to build models based on radiomic and clinical features. A radiomics-clinical nomogram model was developed, and the predictive performance of the models was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. Results A total of 174 patients were included. 2016 radiomic features were extracted from non-contrast CT, and 9 features were selected to build the radiomics model. Univariate and stepwise multivariate analyses identified admission NIHSS score, hemorrhagic transformation, NLR, and admission blood glucose as independent factors for building the clinical model. The AUC of the radiomics-clinical nomogram model in the training and testing cohorts were 0.860 (95%CI 0.801–0.919) and 0.775 (95%CI 0.605–0.945), respectively. Conclusion The radiomics-clinical nomogram model based on non-contrast CT demonstrated satisfactory performance in predicting futile recanalization in patients with anterior circulation acute ischemic stroke.

Abstract Total‐body positron emission tomography (TB‐PET) has significantly advanced from initial conception to global commercial availability. The high sensitivity of TB‐PET has led to superior lesion detection, thereby expanding the range of clinical applications. TB‐PET technology offers several advantages: (a) It enables the detection of small lesions, facilitating precise cancer staging and targeted cancer formulation. (b) The technology shortens the acquisition time while maintaining the quality of diagnostic images. (c) TB‐PET allows for a reduction in the amount of administered radiotracer, which minimizes image noise, reduces the effective radiation dose to patients, and enhances staff safety. (d) The scanner supports the development of new tracers and the dynamic imaging of these tracers throughout the entire body. (e) TB‐PET accommodates delayed scanning, which has been shown to improve the detection of small and previously undetected malignant lesions by enhancing the clearance in areas of significant background activity. (f) Owing to its high‐quality images, TB‐PET is suitable for parametric imaging, which offers several advantages over conventional standardized uptake value imaging. However, TB‐PET still faces several challenges. There is a lack of consensus on the optimal dose and scan duration for clinical diagnosis using TB‐PET. Additionally, unified standards for parametric imaging via TB‐PET are yet to be established, and the full clinical significance of this technology remains under‐explored. The accompanying review (Part 1) covers TB‐PET data manipulation and analysis.

The aim of the current research is to highlight the time-dependent properties of laminar convective thermal transmission inside a semi-infinite pipe, with an emphasis on flow frequencies that impact inter-fluid momentum and energy. The implicit finite difference approach is used to solve two-dimensional mathematical model composed of nonlinear partial differential equations. The research includes forecasting thermal performance of time-dependent flow in a pipe over several parameter ranges relevant to the flow model. The obtained forecasts were emphasized graphically. The numerical solutions were separated into steady and unsteady components, with the steady component yielding findings that were then used to determine the time dependent surface shearness and energy shearness in the time dependent phase. The stable component of the investigation revealed that raising the buoyancy force parameter and the impact of viscous dissipation significantly improved the flow velocity pattern and heat distributions throughout the flow domain. While the amplitude of time dependent surface shearness varied somewhat across various buoyancy force parameter values, the amplitude of time dependent heat transmission rates varied significantly. This study sheds light on the interaction of several characteristics, such as buoyancy force effects and internal energy loss, on time-dependent thermal energy flow inside a semi-infinite pipe subjected to laminar convective flow. It is worth noting that the amplitude of the time dependent rate of heat transmission shows more noticeable variations with different values of the buoyancy force parameter, in contrast to the minute change in the amplitude of the time dependent surface sheerness.

Abstract Objectives 18F-fluorodeoxyglucose (FDG) PET/CT has been widely used for the differential diagnosis of cancer. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may make it difficult to differentiate between benign and malignant lesions. It is crucial to find reliable quantitative metabolic parameters to further support the diagnosis. This study aims to evaluate the value of the quantitative metabolic parameters derived from dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting epidermal growth factor receptor (EGFR) mutation status. Methods We included 147 patients with lung lesions to perform FDG PET/CT dynamic plus static imaging with informed consent. Based on the results of the postoperative pathology, the patients were divided into benign/malignant groups, adenocarcinoma (AC)/squamous carcinoma (SCC) groups, and EGFR-positive (EGFR+)/EGFR-negative (EGFR-) groups. Quantitative parameters including K1, k2, k3, and Ki of each lesion were obtained by applying the irreversible two-tissue compartmental modeling using an in-house Matlab software. The SUV analysis was performed based on conventional static scan data. Differences in each metabolic parameter among the group were analyzed. Wilcoxon rank-sum test, independent-samples T-test, and receiver-operating characteristic (ROC) analysis were performed to compare the diagnostic effects among the differentiated groups. P 0.05, respectively). For ROC analysis, the Ki had a cut-off value of 0.0350 ml/g/min when predicting EGFR status, with a sensitivity of 0.710, a specificity of 0.588, and an AUC of 0.674 [0.523–0.802]. Conclusion Although both techniques were specific, Ki had a greater specificity than SUVmax when the cut-off value was set at 0.0250 ml/g/min for the differential diagnosis of lung cancer. At a cut-off value of 0.0350 ml/g/min, there was a 0.710 sensitivity for EGFR status prediction. If EGFR testing is not available for a patient, dynamic imaging could be a valuable non-invasive screening method.

Abstract Comprehending the complex interplay among urban mobility, human behavior, and the COVID-19 pandemic could deliver vital perspectives to steer forthcoming public health endeavors. In late 2022, China lifted its "Zero-COVID" policy and rapidly abandoned nearly all interventions. It provides a unique opportunity to observe spontaneous mobility changes without government restriction throughout such a pandemic with high infection. Based on 148 million travel data from the public bus, subway, and taxi systems in Shenzhen, China, our analysis reveals discernible spatial discrepancies within mobility patterns. This phenomenon can be ascribed to the heterogeneous responses of mobility behavior tailored to specific purposes and travel modes in reaction to the pandemic. Considering both the physiological effects of virus infection and subjective willingness to travel, a dynamic model is proposed and capable of fitting fine-grained urban mobility. The analysis and model can interpret mobility data and underlying population behavior to inform policymakers when evaluating public health strategies against future large-scale infectious diseases.

Abstract The metabolic implications in Alzheimer’s disease (AD) remain poorly understood. Here, we conducted a metabolomics study on a moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, and brain amyloid-β deposition (n = 421). These features demonstrated synergistic performances across clinical stages and subpopulations and enhanced the differentiation of AD stages beyond demographics and Apolipoprotein E ε4 allele (APOE-ε4). We validated their performances in eight data sets (total n = 7685) obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Memory and Aging Project (ROSMAP). Importantly, identified features are linked to blood ammonia homeostasis. We further confirmed the elevated ammonia level through AD development (n = 1060). Our findings highlight AD as a metabolic disease and emphasize the metabolite-mediated ammonia disturbance in AD and its potential as a signature and therapeutic target for AD.

Species of the family Polycephalomycetaceae grow on insects or entomopathogenic fungi and are distributed from tropical to subtropical regions. This study proposed four new species of hyperparasitic fungi from China based on six molecular markers (ITS, SSU, LSU, TEF-1α, RPB1 and RPB2) phylogenetic analyses and morphological characteristics. The four new species, i.e. Pleurocordyceps litangensis, Polycephalomyces jinghongensis, Po. multiperitheciatae and Po. myrmecophilus, were described and illustrated. Pl. litangensis, exhibiting a hyperparasitic lifestyle on Ophiocordyceps sinensis, differed from Pleurocordyceps other species in producing subulate β-phialides and ovoid or elliptic α-conidia. Po. jinghongensis was distinct from Polycephalomyces other species, being parasitic on Ophiocordyceps sp., as producing oval or long oval-shaped α-conidia and columns of β-conidia. Po. multiperitheciatae differed from Polycephalomyces other species as having synnemata with fertile head, linear β-conidia and parasitic on Ophiocordyceps multiperitheciata. Po. myrmecophilus was distinct from Polycephalomyces other species, being parasitic on the fungus Ophiocordyceps acroasca, as producing round or ovoid α-conidia and elliptical β-conidia without synnemata from the colonies. These four species were clearly distinguished from other species in the family Polycephalomycetaceae by phylogenetic and morphological characteristics. The morphological features were discussed and compared to relevant species in the present paper.

Abstract Background Myeloid-derived suppressor cells (MDSCs) promote tumor growth, metastasis, and lead to immunotherapy resistance. Studies revealed that miRNAs are also expressed in MDSCs and promote the immunosuppressive function of MDSCs. Currently, few studies have been reported on inducible cellular microvesicle delivery of nucleic acid drugs targeting miRNA in MDSCs for the treatment of malignant tumors. Results and conclusion In this study, we designed an artificial DNA named G-quadruplex-enhanced circular single-stranded DNA-9 (G4-CSSD9), that specifically adsorbs the miR-9 sequence. Its advanced DNA folding structure, rich in tandem repeat guanine (G-quadruplex), also provides good stability. Mesenchymal stem cells (MSCs) were prepared into nanostructured vesicles by membrane extrusion. The MSC microvesicles-encapsulated G4-CSSD9 (MVs@G4-CSSD9) was delivered into MDSCs, which affected the downstream transcription and translation process, and reduced the immunosuppressive function of MDSCs, so as to achieve the purpose of treating melanoma. In particular, it provides an idea for the malignant tumor treatment. Graphical Abstract

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a ''semi-extended and pronated'' elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.