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Metal chalcogenide nanoparticles play a vital role in a wide range of applications and are typically stabilized by organic derivatives containing thiol, amine, or carboxyl moieties, where the nonconjugated particle-ligand interfaces limit the electronic interactions between the inorganic cores and organic ligands. Herein, a wet-chemistry method is developed for the facile preparation of stable platinum chalcogenide (S, Se) nanoparticles capped with acetylene derivatives (e.g., 4-ethylphenylacetylene, EPA). The formation of Pt-C≡ conjugated bonds at the nanoparticle interfaces, which is confirmed by optical and X-ray spectroscopic measurements, leads to markedly enhanced electronic interactions between the d electrons of the nanoparticle cores and π electrons of the acetylene moiety, in stark contrast to the mercapto-capped counterparts with only nonconjugated Pt-S- interfacial bonds, as manifested in spectroscopic measurements and density functional theory calculations. This study underscores the significance of conjugated anchoring linkages in the stabilization and functionalization of metal chalcogenides, a unique strategy for diverse applications.

Carbon-based functional nanocomposites have emerged as potent antimicrobial agents and can be exploited as a viable option to overcome antibiotic resistance of bacterial strains. In the present study, graphitic carbon nitride nanosheets are prepared by controlled calcination of urea. Spectroscopic measurements show that the nanosheets consist of abundant carbonyl groups and exhibit apparent photocatalytic activity under UV photoirradiation towards the selective production of singlet oxygen. Therefore, the nanosheets can effectively damage the bacterial cell membranes and inhibit the growth of bacterial cells, such as Gram-negative Escherichia coli, as confirmed in photodynamic, fluorescence microscopy, and scanning electron microscopy measurements. The results from this research highlight the unique potential of carbon nitride derivatives as potent antimicrobial agents.

The multifaceted chemo-immune resistance is the principal barrier to achieving cure in cancer patients. Identifying a target that is critically involved in chemo-immune-resistance represents an attractive strategy to improve cancer treatment. iRhom1 plays a role in cancer cell proliferation and its expression is negatively correlated with immune cell infiltration. Here we show that iRhom1 decreases chemotherapy sensitivity by regulating the MAPK14-HSP27 axis. In addition, iRhom1 inhibits the cytotoxic T-cell response by reducing the stability of ERAP1 protein and the ERAP1-mediated antigen processing and presentation. To facilitate the therapeutic translation of these findings, we develop a biodegradable nanocarrier that is effective in codelivery of iRhom pre-siRNA (pre-siiRhom) and chemotherapeutic drugs. This nanocarrier is effective in tumor targeting and penetration through both enhanced permeability and retention effect and CD44-mediated transcytosis in tumor endothelial cells as well as tumor cells. Inhibition of iRhom1 further facilitates tumor targeting and uptake through inhibition of CD44 cleavage. Co-delivery of pre-siiRhom and a chemotherapy agent leads to enhanced antitumor efficacy and activated tumor immune microenvironment in multiple cancer models in female mice. Targeting iRhom1 together with chemotherapy could represent a strategy to overcome chemo-immune resistance in cancer treatment.

Objective: The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment. Methods: PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups. Results: Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR) 10 mg = 0.390 (95% confidence interval {CI}, 0.201–0.756), P = 0.005; HR 12 mg = 0.397 (0.208–0.756), P = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 vs. 82 days, HR 10 mg = 0.445 (0.210–0.939), P = 0.034; HR 12 mg = 0.369 (0.174–0.784), P = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 vs. 41 days, HR 10 mg = 0.340 (0.156–0.742), P = 0.007; HR 12 mg = 0.340 (0.159–0.727), P = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases. Conclusions: Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.

Abstract Aims The present study aims to develop a nano-delivery system that encapsulates berberine (BBR) into PLGA-based nanoparticles (BPL-NPs), to treat ulcerative colitis (UC). Furthermore, the therapeutic efficacy and molecular targeting mechanisms of BPL-NPs in the management of UC are thoroughly examined. Methods Emulsion solvent-driven methods were used to self-assemble BBR and PLGA into nanoparticles, resulting in the development of the nano-delivery system (BPL-NPs). The therapeutic effectiveness of BPL-NPs was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice and a lipopolysaccharide (LPS)-induced model of inflammation in THP-1 macrophages. The interaction between Mφs and NCM-460 cells was investigated using a co-culture system. The molecular targeting ability of BPL-NPs in the treatment of UC was validated through in vitro as well as in vivo experiments. Results The BPL-NPs demonstrated a particle size of 184 ± 22.4 nm, enhanced dispersibility in deionized water, and a notable encapsulation efficiency of 31.1 ± 0.2%. The use of BPL-NPs clearly improved the clinical symptoms and pathological changes associated with UC in mice while also ensuring minimal toxicity. In addition, BPL-NPs improved intestinal epithelial cell apoptosis and enhanced the function of the intestinal barrier by inhibiting M1 Mφs infiltration and IL-6 signaling pathway in mice with UC. Furthermore, the BPL-NPs were found to selectively target the IL-6/IL-6R axis during the M1 Mφs-induced apoptosis of NCM460 cells. Conclusion The BPL-NPs were confirmed to harbor anti-inflammatory effects both in vitro and in vivo, along with enhanced water solubility and bioactivity. In addition, the precise targeting of the IL-6/IL-6R axis was confirmed as the mechanism by which the BPL-NPs exerted therapeutic effects in UC, as demonstrated in both in vitro as well as in vivo studies. Graphical Abstract

Abstract Background Physical activity (PA) was strongly associated with health status, with fewer related studies in adolescents (12–19 years). Most current studies using questionnaires to assess PA levels were not objective enough. So, this study used a wearable device to assess PA levels quantitatively and focused on the association between PA levels and self-reported 4 health status among adolescents. Methods Data were obtained from adolescents (2241) with both PA and health status assessments from two cycles of NHANES, 2011–2014, using a wearable accelerometer-based device to assess PA levels quantitatively, MIMS-units as the metric, averaging over all valid days of wear (MIMS-units average). There were 4 health statuses, including (1) whether or not flu, pneumonia, or ear infection, (2) whether or not stomach or intestinal illness, (3) whether or not head cold or chest cold, and (4) general health condition, from the past 30 days self-reported. Weighted multiple logistic regression was used to analyze the association between the 4 health statuses and the MIMS-units average and MIMS-units average quartiles respectively. Subgroup analyses were also conducted on age, sex, BMI, and race. Results After controlling confounding factors, there was no significant correlation between the MIMS-units average and the four physical health conditions in Table 3 model 3. While MIMS-units average quartiles results showed that compared to lower PA levels (Q1), higher PA levels (Q4) were linked to a lower incidence of “flu”(OR = 0.94, 95% CI [0.91, 0.99], P

In light of the escalating global energy imperatives, mining of challenging-to-access resources, such as steeply inclined extra-thick coal seams (SIEC), has emerged as one of the future trends within the domain of energy advancement. However, there is a risk of gas and coal spontaneous combustion coupling disasters (GCC) within the goaf of SIEC due to the complex goaf structure engendered by the unique mining methodologies of SIEC. To ensure that SIEC is mined safely and efficiently, this study conducts research on the GCC within the goaf of SIEC using field observation, theoretical analysis, and numerical modeling. The results demonstrate that the dip angle, the structural dimensions in terms of width-to-length ratio, and compressive strength of the overlying rock are the key factors contributing to the goaf instability of SIEC. The gangue was asymmetrically filled, primarily accumulating within the central and lower portions of the goaf, and the filling height increased proportionally with the advancing caving height, the expansion coefficient, and the thickness of the surrounding rock formation. The GCC occurs in the goaf of SIEC, with an air-return side range of 41 m and an air-intake side range of 14 m, at the intersection area of the “”-shaped gas concentration distribution (gas explosion). The optimal nitrogen flow rate is 1000 m3/h with an injection port situated 25 m away from the working face for the highest nitrogen diffusion efficacy and lowest risk of gas explosion, coal spontaneous combustion, and GCC. It has significant engineering applications for ensuring the safe mining of SIEC threatened by the GCC.

Abstract Recent research highlights that non-exhaust emissions from the abrasion of tires and other organic materials have emerged as a substantial source of airborne particulate matter and marine microplastics. Despite their growing impact, the underlying mechanisms driving these abrasion emissions have remained largely unexplored. In this study, we uncover that abrasion emissions from organic materials are fundamentally governed by a fatigue fracture process, wherein particles are progressively detached from the material surface under cyclic abrasion loads. Our findings demonstrate that these emissions increase significantly only when the applied abrasion loads surpass the material’s toughness threshold. We establish a scaling relationship between the concentration of emitted particulate matter and the measurable crack propagation rate of the organic material, offering a robust quantitative method to estimate abrasion emissions. This work not only introduces a novel mechanistic framework for understanding particulate matter pollution from organic material abrasion but also provides a scientific basis for developing strategies to mitigate emissions of airborne particulates and marine microplastics.

ABSTRACT Introduction: We aim to compare the safety and effectiveness of the KangDuo (KD)-Surgical Robot-01 (KD-SR-01) system and the da Vinci (DV) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This multicenter prospective randomized controlled trial was conducted between March 2022 and September 2023. Group 1 included 29 patients undergoing KD-RARNU. Group 2 included 29 patients undergoing DV-RARNU. Patient demographic and clinical characteristics, perioperative data, and follow-up outcomes were collected prospectively and compared between the two groups. Results: There were no significant differences in patient baseline demographic and preoperative characteristics between the two groups. The success rates in both groups were 100% without conversion to open or laparoscopic surgery or positive surgical margins. No significant difference was observed in docking time [242 (120-951) s vs 253 (62-498) s, P = 0.780], console time [137 (55-290) min vs 105 (62-220) min, P = 0.114], operative time [207 (121-460) min vs 185 (96-305) min, P = 0.091], EBL [50 (10-600) mL vs 50 (10-700) mL, P = 0.507], National Aeronautics and Space Administration Task Load Index scores, and postoperative serum creatinine levels between the two groups. None of the patients showed evidence of distant metastasis, local recurrence, or equipment-related adverse events during the four-week follow-up. One (3.4%) patient in Group 2 experienced postoperative enterovaginal and enterovesical fistulas (Clavien-Dindo grade III). Conclusions: The KD-SR-01 system is safe and effective for RARNU compared to the DV Si or Xi system. Further randomized controlled studies with larger sample sizes and longer durations are required.

The utilization of heavy-panicle hybrid rice exemplifies the successful integration of architectural enhancement and heterosis, which has been widely adopted in the southwest rice-producing area of China. Iterative improvement in disease resistance and grain quality of heavy-panicle hybrid rice varieties is crucial to promote their sustainable utilization. Here, we performed a molecular design breeding strategy to introgress beneficial alleles of broad-spectrum disease resistance and grain quality into a heavy-panicle hybrid backbone restorer line Shuhui 600 (R600). We successfully developed introgression lines through marker-assisted selection to pyramid major genes (Wxb + ALKA-GC + Pigm + Xa23) derived from three parents (Huanghuazhan, I135, I488), which significantly enhance grain quality and confer resistance to rice blast and bacterial blight (BB). The improved parental R600 line (iR600) exhibited superior grain quality and elevated disease resistance while maintaining the heavy-panicle architecture and high-yield capacity of R600. Moreover, the iR600 was crossed with male sterility line 608A to obtain a new heavy-panicle hybrid rice variety with excellent eating and cooking quality (ECQ) and high yield potential. This study presents an effective breeding strategy for rice breeders to expedite the improvement of grain quality and disease resistance in heavy-panicle hybrid rice.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy, using common laboratory and transthoracic echocardiography indices.Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and September 2022, were included. General patient information, laboratory test results, and transthoracic echocardiography data were collected. After feature extraction, five machine learning algorithms, including random forest (RF), gradient boosting (GB), support vector machine (SVM), K-nearest neighbor (KNN), and decision tree (DT), were applied to construct a prediction model for the changes of the patients′ metabolic state after neoadjuvant therapy, and the prediction performances of the five models were compared.Results·A total of 232 cases with valid clinical data were included, comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy. Feature extraction identified five key features: white blood cell count, hemoglobin, high-density lipoprotein (HDL), interleukin-2 receptor, and interleukin-8. In the multi-feature analysis, the area under the receiver operating characferistic curve (AUC) was higher in the combination of white blood cell count, hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8 (RF: 0.928 vs 0.772, GB: 0.900 vs 0.792, SVM: 0.941 vs 0.764, KNN: 0.907 vs 0.762, DT: 0.799 vs 0.714). The RF, SVM, and GB models showed higher AUC (0.928, 0.941, 0.900) and accuracy (0.914, 0.897, 0.776). The SVM model exhibited superior accuracy in the training data compared to the RF and GB models (P=0.394, 0.122 and 0.097, respectively).Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators, namely, white blood cell count, hemoglobin, high-density lipoprotein, interleukin-2 receptor, and interleukin-8. SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient′s inflammatory metabolic state.

Abstract The development of high-performance metal-free organic X-ray scintillators (OXSTs), characterized by a synergistic combination of robust X-ray absorption, efficient exciton utilization, and short luminescence lifetimes, poses a considerable challenge. Here we present an effective strategy for achieving augmented X-ray scintillation through the utilization of halogenated open-shell organic radical scintillators. Our experimental results demonstrate that the synthesized scintillators exhibit strong X-ray absorption derived from halogen atoms, display efficacious X-ray stability, and theoretically achieve 100% exciton utilization efficiency with a short lifetime (∼18 ns) due to spin-allowed doublet transitions. The superior X-ray scintillation performance exhibited by these organic radicals is not only exploitable in X-ray radiography for contrast imaging of various objects but also applicable in a medical high-resolution micro-computer-tomography system for the clear visualization of fibrous veins within a bamboo stick. Our study substantiates the promise of organic radicals as prospective candidates for OXSTs, offering valuable insights and a roadmap for the development of advanced organic radical scintillators geared towards achieving high-quality X-ray radiography.

In order to further explore the hydrogeological conditions of Baotashan sandstone aquifer in Ningdong coalfield and provide basic data for the water disaster prevention and control of the lower coal floor sandstone, the hydrogeological parameters of the aquifer were calculated by dewatering test, and the feasibility of water drainage from aquifer was proved. The results show that: according to the data of dewatering borehole and one observation borehole, two observation boreholes from single borehole dewatering test of Baotashan sandstone, the average permeability coefficient calculated by analytical method is 0.301 m/d and 0.219 m/d, and the average influence radius is 691 m and 914 m, respectively. The average influence radius obtained by graphic method is 697 m, and the unit water inflow is 0.071-0.088 L/(s·m) according to three times of deep drawdown. The hydrogeological parameters obtained by dewater test are large than those obtained by pumping water test. The hydrogeological characteristics of Baotashan sandstone aquifer are weak permeability and water abundance, the water abundance is uneven, and the pressure and water temperature are high. Based on the results of dewater test and the analysis of boundary conditions in the study area, it is found that Baotashan sandstone aquifer has good drainage ability.

Abstract Background Long noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy. Methods We analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy. Results We determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis. Conclusions Our results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

Abstract Purpose Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. Patients and methods Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. Results Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. Conclusions Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA.

Optical imaging in the second near-infrared (NIR-II; 900–1880 nm) window is currently a popular research topic in the field of biomedical imaging. This study aimed to explore the application value of NIR-II fluorescence imaging in foot and ankle surgeries. A lab-established NIR-II fluorescence surgical navigation system was developed and used to navigate foot and ankle surgeries which enabled obtaining more high-spatial-frequency information and a higher signal-to-background ratio (SBR) in NIR-II fluorescence images compared to NIR-I fluorescence images; our result demonstrates that NIR-II imaging could provide higher-contrast and larger-depth images to surgeons. Three types of clinical application scenarios (diabetic foot, calcaneal fracture, and lower extremity trauma) were included in this study. Using the NIR-II fluorescence imaging technique, we observed the ischemic region in the diabetic foot before morphological alterations, accurately determined the boundary of the ischemic region in the surgical incision, and fully assessed the blood supply condition of the flap. NIR-II fluorescence imaging can help surgeons precisely judge surgical margins, detect ischemic lesions early, and dynamically trace the perfusion process. We believe that portable and reliable NIR-II fluorescence imaging equipment and additional functional fluorescent probes can play crucial roles in precision surgery.

Abstract Background The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China’s Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. Methods A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. Results Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. Conclusions With Ningbo’s strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Energy-intensive technologies and high-precision research require energy-efficient techniques and materials. Lens-based optical microscopy technology is useful for low-energy applications in the life sciences and other fields of technology, but standard techniques cannot achieve applications at the nanoscale because of light diffraction. Far-field super-resolution techniques have broken beyond the light diffraction limit, enabling 3D applications down to the molecular scale and striving to reduce energy use. Typically targeted super-resolution techniques have achieved high resolution, but the high light intensity needed to outperform competing optical transitions in nanomaterials may result in photo-damage and high energy consumption. Great efforts have been made in the development of nanomaterials to improve the resolution and efficiency of these techniques toward low-energy super-resolution applications. Lanthanide ion-doped upconversion nanoparticles that exhibit multiple long-lived excited energy states and emit upconversion luminescence have enabled the development of targeted super-resolution techniques that need low-intensity light. The use of lanthanide ion-doped upconversion nanoparticles in these techniques for emerging low-energy super-resolution applications will have a significant impact on life sciences and other areas of technology. In this review, we describe the dynamics of lanthanide ion-doped upconversion nanoparticles for super-resolution under low-intensity light and their use in targeted super-resolution techniques. We highlight low-energy super-resolution applications of lanthanide ion-doped upconversion nanoparticles, as well as the related research directions and challenges. Our aim is to analyze targeted super-resolution techniques using lanthanide ion-doped upconversion nanoparticles, emphasizing fundamental mechanisms governing transitions in lanthanide ions to surpass the diffraction limit with low-intensity light, and exploring their implications for low-energy nanoscale applications.

Abstract Magnons and phonons are engineered in artificial lattices with tunable modes and band dispersions. Recent advance in magnon-phonon coupling shined a light on combining magnonic and phononic crystals as hybrid magnon-phonon crystals, benefit from the tunable magnon-phonon coupling, the time-reversal symmetry breaking of magnons, and the long lifetime of phonons. This perspective summarizes lattice-based mutual control of magnons and phonons, and proposes the opportunities provided by the hybrid magnon-phonon crystals.

Background Promoting the construction of county-level medical communities is a crucial measure for establishing a hierarchical medical system. While the domestic academic community has conducted extensive theoretical and empirical research in this field, there is a lack of comprehensive summaries of existing research findings. This study uses bibliometric methods to systematically review the progress of related literature in this field, providing insights and references for the high-quality development of county-level medical communities. Objective To conduct a visual analysis of the literature on county-level medical communities in China, exploring research hotspots and frontier trends in this field. Methods Using the China National Knowledge Infrastructure (CNKI) database, literature related to county-level medical communities published between 2016 and 2023 was retrieved on February 25, 2024. CiteSpace software was employed for bibliometric visualization analysis of the literature, focusing on publication years, authors and institutions, keyword co-occurrence, clustering, timeline distribution, and burst detection. Results A total of 481 articles were included. The publication volume in this field has been increasing, driven by policy factors, with 65 articles (13.51%) published between 2016 and 2019, 167 articles (34.72%) published between 2020 and 2021, and 249 articles (51.77%) published between 2022 and 2023. The top three authors in terms of publication volume were CHEN Yingchun, WANG Fang, and ZHENG Ying, each with 8 articles. The top two keywords in terms of centrality and cluster size are "medical community" and "hierarchical medical system". The timeline distribution indicated that "hierarchical medical system" was the earliest and most sustained research hotspot in this field. Additionally, clusters such as "integration of medical prevention" "performance evaluation" "countermeasures" and "patients" emerged as research hotspots. Burst detection revealed that "medical insurance fund" "chronic disease" "management model" "development strategy" and "rural doctors" were recent research hotspots and future directions in this field. Conclusion Key research hotspots in the field of county-level medical communities include the construction of hierarchical medical systems, focusing on chronic diseases and the integration of public health services, and exploring performance evaluation pathways. Future research trends indicate a strong focus on deepening policy research, using county-level medical community construction to promote the establishment of hierarchical medical systems, advancing innovation in the integration of medical prevention, enhancing performance evaluation, and optimizing internal management.

Streptomyces mobaraenesis transglutaminase (smTG) can be used for site-specific labeling of proteins with chemical groups. Here, we explored the use of modified smTG for the biosynthesis of nanobody-fluorophore conjugates (NFC). smTG catalyzes the conjugation of acyl donors containing glutamine with lysine-containing acceptors, which can lead to non-specific cross-linking. To achieve precise site-specific labeling, we employed molecular docking and virtual mutagenesis to redesign the enzyme's substrate specificity towards the peptide GGGGQR, a non-preferred acyl donor for smTG. Starting with a thermostable and highly active smTG variant (TGm2), we identified that single mutations G250H and Y278E significantly enhanced activity against GGGGQR, increasing it by 41 % and 1.13-fold, respectively. Notably, the Y278E mutation dramatically shifted the enzyme's substrate preference, with the activity ratio against GGGGQR versus the standard substrate CBZ-Gln-Gly rising from 0.05 to 0.93. In case studies, we used nanobodies 1C12 and 7D12 as labeling targets, catalyzing their conjugation with a synthetic fluorophore via smTG variants. Nanobodies fused with GGGGQR were successfully site-specifically labeled by TGm2-Y278E, in contrast to non-specific labeling observed with other variants. These results suggest that engineering smTG for site-specific labeling is a promising approach for the biosynthesis of antibody-drug conjugates.

AbstractContext Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects.Objective To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN.Materials and methods Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated.Results DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKβ (0.93-fold), p-IKKβ (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold).Discussion and conclusions The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.