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During dislocation, a tunnel crossing the active fault will be damaged to varying degrees due to its permanent stratum displacement. Most previous studies did not consider the influence of the tunnel’s deep burial and the high in-situ stress, so the results were not entirely practical. In this paper, the necessity of solving the anti-dislocation problem of deep-buried tunnels is systemically discussed. Through the model test of tunnels across active faults, the differences in failures between deep-buried tunnels and shallow-buried tunnels were compared, and the dislocation test of deep-buried segmental tunnels was carried out to analyze the external stress change, lining strain, and failure mode of tunnels. The results are as follows. (1) The overall deformation of deep-buried and shallow-buried tunnels is both S-shaped. The failure mode of deep-buried tunnels is primarily characterized by shear and tensile failure, resulting in significant compressive deformation and a larger damaged area. In contrast, shallow-buried tunnels mainly experience shear failure, with the tunnel being sheared apart at the fault crossing, leading to more severe damage. (2) After the segmental structure design of the deep-buried tunnel, the “S” deformation pattern is transformed into a “ladder” pattern, and the strain of the tunnel and the peak stress of the external rock mass are reduced; therefore, damages are significantly mitigated. (3) Through the analysis of the distribution of cracks in the tunnel lining, it is found that the tunnel without a segmental structure design has suffered from penetrating failure and that cracks affect the entire lining. The cracks in a flexible segmental tunnel affect about 66.6% of the entire length of the tunnel, and cracks in a tunnel with a short segmental tunnel only affect about 33.3% of the entire length of the tunnel. Therefore, a deep-buried tunnel with a short segmental tunnel can yield a better anti-dislocation effect. (4) By comparing the shallow-buried segmental tunnel in previous studies, it is concluded that the shallow-buried segmental tunnel will also suffer from deformation outside the fault zone, while the damages to the deep-buried segmental tunnel are concentrated in the fault zone, so the anti-dislocation protection measures of the deep-buried tunnel shall be provided mainly in the fault zone. The results of the above study can provide theoretical reference and technical support for the design and reinforcement measures of the tunnel crossing active fault under high in-situ stress conditions.

Abstract Epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases. In the current study, we investigated the role of circRNA HIPK3 (circHIPK3) in EMT process of RPE cells (RPE-EMT). circHIPK3 is one abundant circRNA generated from the second exon of HIPK3 mRNA. We found that circHIPK3 expression was significantly increased in TGF-β1-induced RPE-EMT model. Silencing of circHIPK3 attenuated TGF-β1-induced RPE-EMT process, whereas forced expression of circHIPK3 could trigger EMT in RPE cells. Mechanistically, circHIPK3 regulates RPE-EMT process via sponging multiple microRNAs (miRNAs). This study provides novel insights into the mechanism of RPE-EMT. Targeting circHIPK3 might serve as a therapeutic strategy in RPE-EMT associated vitreoretinal diseases.

Abstract By analyzing the composite effects of the plastic shear strain and confining stress according to the laboratory test results, a model adopting a deteriorating elastic modulus for the intact rock is proposed. Soft rock such as coal and the strong rock such as granite with different quality are investigated. Geological Strength Index (GSI) is adopted to represent the integrity of rock, to be specific, from intact rock to the rock mass. Specifically, for the strain-softening rock mass, the elastic modulus is gained by introducing GSI into the deterioration model. The strength parameters are obtained by fitting GSI into Hoek-Brown failure criterion. Then, the elastic modulus and strength parameters of the rock mass are employed in the numerical procedure for solving out the rock deformation, the radii of the plastic softening and residual zones of the tunnels. The rationality of the numerical procedure is verified with the existing semi-analytical and analytical procedures. In the discussion, the influences of the critical plastic parameters and GSI, on the elastic modulus, rock deformation, radii of the plastic softening and residual zones are investigated. Five models for the variation of the modulus including the proposed deterioration model are defined. The rock mass deformation behaviours of the five models are compared. The results indicate that, in the plastic softening zone that is far away from the tunnel periphery, the elastic modulus is more sensitive to the plastic shear strain, whereas near the tunnel periphery, the elastic modulus is primarily affected by the confining stress. Regarding a linear decrease of the elastic modulus versus the plastic shear strain overestimates the elastic modulus to some extent, especially for the soft rock mass.

Abstract Combing macroscopic experimental method and mesoscopic numerical method, this study analyses the strain-softening behaviours of granite and sandstone. From the macroscopic perspective, the stress–strain curves of granite and sandstone under different confining pressures are studied by laboratory triaxial compression test. Variations of post-peak reduction modulus and critical plastic shear strain versus confining stress are obtained. Evolution of strength parameters at peak, residual and strain-softening stage are proposed. Then a method to develop the strain-softening model of hard and soft rocks is presented. From the mesoscopic perspective, based on the laboratory test results, the parameters of discrete element method PFC for the samples of the granite and sandstone are calibrated. Comparing the basically consistent results of laboratory experiment and numerical simulation, the feasibility of discrete element method is verified. Evolutions of mesoscopic crack propagation and mesoscopic particle displacement field in the complete failure process are analysed. Typical stresses of granite sample and sandstone sample in the failure stage are investigated. Above combined macroscopic experimental method and mesoscopic numerical method systematically analyse the characteristics of hard rock and soft rock in the strain-softening stage. Failure process and mechanical property of hard rock and soft rock are revealed at the macroscopic and mesoscopic levels. The initiation and propagation process of micro-cracks in rock are thoroughly investigated. The research results provide a scientific foundation for the analyse of strain-softening behaviour of hard rock and soft rock. The result shows that both the mesoscopic numerical method and macroscopic experimental method indicate that the failure pattern of sandstone is influenced by both confining pressure and axial stress, while granite is mainly affected by axial stress.

Abstract Melatonin supplementation during in vitro maturation (IVM) improves porcine oocyte maturation and embryonic development by exerting antioxidative effects. Nevertheless, the mechanism by which melatonin prevents polyspermy after in vitro fertilization (IVF) remains unclear. Here, we examined the effects of melatonin on cytoplasmic maturation and the incidence of polyspermic penetration in porcine oocytes. No statistically significant difference was observed in the rate of first polar body formation between the groups (Control, Melatonin, Melatonin + Luzindole, and Melatonin + 4-P-PDOT). Interestingly, melatonin supplementation significantly improved the cytoplasmic maturation of porcine oocytes by enhancing the normal distribution of organelles (Golgi apparatus, endoplasmic reticulum and mitochondria) and upregulating organelle-related gene expressions (P

Abstract In this paper, we give a proof of 5D A n AGT conjecture at β = 1, where the gauge theory side is one dimension higher than the original 4D case, and corresponds to the q-deformation of the 2D conformal field theory side. We define a q-deformed A n Selberg integral, which generalizes the A n Selberg integral and the q-deformed A 1 Selberg integral in the literature. A q-deformed A n Selberg average formula with n + 1 Schur polynomials is proposed and proved to complete the proof.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Abstract Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression. Based on this data, we constructed SNSCC prognosis pathways and performed a gene set enrichment analysis (GSEA). Clear operative margins were linked to a 73.5–86.3% improvement in overall survival and a 73.5–88.9% lower risk of recurrence. Nasal cavity-originated cases exhibited a 67.6–97.4% decrease in mortality and an 80.7–96.7% lower recurrence rate. Patients at T1-2 staging had a 65.0–80.6% reduced risk of death and recurrence compared to those at T3 stage. Additionally, we identified 53 genes associated with SNSCC, with 14 also implicated in primary tumor site, T stage, and operative margin. These genes, including EGFR, PIK3CA, ERBB2, PTEN, BCL2, BRAF, KRAS, and PRL, form a complex SNSCC-prognosis pathway and were significantly enriched in 42 KEGG pathways and Gene Ontology (GO) terms (FDR-corrected p-value

Abstract Background Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial registration Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Introduction: Essential tremor is a common movement disorder. Numerous validated clinical rating scales exist to quantify essential tremor severity by employing rater-dependent visual observation but have limitations, including the need for trained human raters and the lack of precision and sensitivity compared to technology-based objective measures. Other continuous objective methods to quantify tremor amplitude have been developed, but frequently provide unitless measures (e.g., tremor power), limiting real-world interpretability. We propose a novel algorithm to measure kinetic tremor amplitude using digital spiral drawings, applying the V3 framework (sensor verification, analytical validation, and clinical validation) to establish reliability and clinical utility. Methods: Archimedes spiral drawings were recorded on a digitizing tablet from participants (n = 7) enrolled in a randomized placebo control double-blinded crossover pilot trial evaluating the efficacy of oral cannabinoids in reducing essential tremor. We developed an algorithm to calculate the mean and maximum tremor amplitude derived from the spiral tracings. We compared the digitally measured tremor amplitudes to manual measurement to evaluate sensor reliability, determined the test-retest reliability of the digital output across two short-interval repeated measures, and compared the digital measure to kinetic tremor severity graded using The Essential Tremor Rating Assessment Scale (TETRAS) score for spiral drawings. Results: This algorithm for automated assessment of kinetic tremor amplitude from digital spiral tracings demonstrated a high correlation with manual spot measures of tremor amplitude, excellent test-retest reliability, and a high correlation with human ratings of the TETRAS score for spiral drawing severity when the tremor severity was rated “slight tremor” or worse. Discussion: This digital measure provides a simple and clinically relevant evaluation of kinetic tremor amplitude that shows promise as a potential future endpoint for use in clinical trials of essential tremor.

Abstract Metasurfaces are capable of fully reshaping the wavefronts of incident beams in desired manners. However, the requirement for external light excitation and the resonant nature of their meta-atoms, make challenging their on-chip integration. Here, we introduce the concept and design of a fresh class of metasurfaces, driven by unidirectional guided waves, capable of arbitrary wavefront control based on the unique dispersion properties of unidirectional guided waves rather than resonant meta-atoms. Upon experimentally demonstrating the feasibility of our designs in the microwave regime, we numerically validate the introduced principle through the design of several microwave meta-devices using metal-air-gyromagnetic unidirectional surface magneto-plasmons, agilely converting unidirectional guided modes into the wavefronts of 3D Bessel beams, focused waves, and controllable vortex beams. We, further, numerically demonstrate sub-diffraction focusing, which is beyond the capability of conventional metasurfaces. Our unfamiliar yet practical designs may enable full, broadband manipulation of electromagnetic waves on deep subwavelength scales.

Abstract Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan–Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29–84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5–16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2–122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time.

Objective The development of overhead property in urban rail transit vehicle bases becomes a basic requirement for vehicle base design in many cities such as Shanghai and Beijing. To effectively address the impact of overhead property development on the covered garage s, it is necessary to study the clearance height of operation inspection garage. Method Taking the operation garage and the joint garage of vehicle base as research objects, the main factors affecting the clearance height of vehicle base garage with overhead property are analyzed, and the design process of operation inspection garage clearance height is sorted. Calculation methods for operation inspection garage clearance height under overhead catenary system and third contact rail system are proposed respectively. Result & Conclusion When using overhead catenary system, factors such as the height and safety distance of catenary wires, the top elevation of crane running track, the crane height, the overhead pipeline layer height, and structural main beam height need to be considered. The minimum height of the first-floor slab of parking inspection garage is 7.5 m; for inspection garages (excluding parking inspection and temporary repair garages), the first-floor slab height is uniformly set at 8.5 m; the minimum height of the first-floor slab of temporary repair garage is 13.5 m. When using contact rail system, apart from the height of catenary wires, the other influencing factors are consistent with the overhead catenary system. The first-floor slab heights of parking inspection and weekly/monthly inspection garages are 7.5 m and 8.5 m respectively.

The dimorphic fungus Histoplasma capsulatum, which almost exclusively resides within host phagocytic cells during infection, must meet its nutritional needs by scavenging molecules from the phagosome environment. The requirement for gluconeogenesis, but not fatty acid catabolism, for intracellular growth, implicates amino acids as a likely intracellular nutrient source. Consequently, we investigated Histoplasma growth on amino acids. Growth assays demonstrated that Histoplasma yeasts readily utilize most amino acids as nitrogen sources but only efficiently catabolize glutamine, glutamate, aspartate, proline, isoleucine, and alanine as carbon sources. An amino acid permease-based conserved domain search identified 28 putative amino acid transporters within the Histoplasma genome. We characterized the substrate specificities of the major Histoplasma amino acid transporters using a Saccharomyces cerevisiae heterologous expression system and found that H. capsulatum Dip5, Gap3, and a newly described permease, Gai1, comprise most of Histoplasma’s amino acid import capacity. Histoplasma yeasts deficient in these three transporters are impaired for growth on free amino acids but proliferate within macrophages and remain fully virulent during infection of mice, indicating that free amino acids are not the principal nutrient source within the phagosome to support Histoplasma proliferation during infection.

Objective Hematuria is one of the most common conditions in children, and increase the risk of chronic kidney disease. Persistent hematuria may be the earliest manifestation of type IV collagen-related nephropathy. Early diagnosis is essential for optimized therapy. Due to the invasive nature of kidney biopsy and the high cost of whole exome sequencing, its application in the diagnosis of isolated hematuria is rare. Hence, we performed noninvasive and convenient genetic testing approaches for type IV collagen-related nephropathy.Methods We used noninvasive oral mucosa sampling as an alternative method for DNA isolation for genetic testing and designed a panel targeting three type IV collagen nephropathy-related genes in children with hematuria. Children with persistent hematuria unaccompanied by clinically significant proteinuria or renal insufficiency who underwent genetic testing using a hematuria panel were enrolled.Results Thirty-seven of 112 (33.0%) patients were found to have a genetic variant in COL4A3/A4/A5. Pathogenic/likely pathogenic COL4A3/A4/A5 variants were identified in 17 of the 112 patients analyzed (15.2%), which were considered to explain their hematuria manifestations. In addition, variants of unknown significance (VUSs) were found in 17.8% (20/112) of patients. Furthermore, we observed a much greater COL4A3/A4/A5 variant detection rate in patients with a positive family history or more severe hematuria (RBC ≥ 20/HP) or with coexisting microalbuminuria (59.2% vs. 12.7%, p

Rapid decline in Arctic summer sea ice cover has brought new opportunities for shipping and resource exploitation in the Arctic, and accurate determination of summer sea ice conditions has become increasingly important. Knowledge of sea ice velocity (SIV) is crucial for ice engineering and navigation in the Arctic. This study retrieved SIV in summer based on the polarization difference (PD) of brightness temperatures (TBs) at 36 GHz derived from the recalibrated FY-3D satellite microwave radiometer data FY-3D/MWRI. Compared with swath TB data, swath PD data can better suppress the noise associated with atmospheric wetness (cloud liquid water and water vapor). Moreover, different from the arbitrary template selection scheme used in current algorithms, we propose an optimized template selection scheme based on the image texture, which considers the frequent deformation processes of sea ice in summer. Determination of SIV using templates with irregular distribution presents lower uncertainty and higher computational efficiency compared with templates with regular distribution. Based on the improved algorithm, this study obtained either swath irregular SIV fields with nominal spatial resolution of 30 km or daily gridded SIV fields with 50-km spatial resolution in summer 2019 using 36-GHz PDs.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127−CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Modular multilevel converter (MMC)-based high-voltage DC (HVDC) systems have found rapid growth in power grids. To reduce the inrush current, it is necessary to precharge the submodule (SM) capacitors to the rated voltage before normal operation. In this paper, an optimized pre-charging strategy for MMC is proposed based on power balancing . First, the charging power is obtained by a designed closed-loop control of the SM capacitors. Then the total power released by the AC or DC side could be calculated by power conservation and feedback by controlling the charging current. At the same time, the power difference between the upper and lower bridge arm of each phase and the internal voltage balancing of bridge arms are also considered by the proposed bridge arm and SM voltage algorithms. By comparing with conventional closed-loop pre-charging strategies, the pre-charging speed is greatly enhanced as the achievement of synchronous charging of upper and lower bridge arm SMs. Moreover, as the same voltage and current double closed-loop control applied in both MMC pre-charging and normal state, the state transition time could be reduced. Finally, a series of simulations and prototype experiments are conducted to verify the feasibility of the proposed pre-charging strategy.

ABSTRACTWith the rapid expansion of urbanization, it is imperative to monitor built-up areas changes to promote the sustainable development of cities, aligning with the goals of Sustainable Development Goal 11(SDG 11). Remote sensing big data is valuable for automatically mapping these changes. Bi-temporal very high-resolution (Bi-VHR) optical images have been widely utilized for fine-grained change detection (CD). However, the significant spatiotemporal inconsistency due to imaging conditions and seasonal variations poses challenges for VHR optical CD. Unlike optical images, synthetic aperture radar (SAR) images are unaffected by atmospheric interference and provide robust spatiotemporal features as a supplement. Previous CD algorithms with SAR overlooked the exploration of long-term features of time series. In this study, we propose a novel CD framework combining long-term SAR with Bi-VHR images. It incorporates a spatial-frequency learning module to enhance SAR temporal features and a multisource feature fusion module to adaptively fuse the heterogeneous features. The experiments are conducted on OS-BCD dataset, which is the first dataset specifically designed for this task. The results demonstrate that our proposal outperforms advanced CD methods with F1 score, IoU and OA of 64.99%, 48.13%, and 95.11%, validating the efficacy of our proposal in accurately detecting changes in built-up areas.

ABSTRACTInformation on Arctic sea-ice motion in summer is critical for operational sea-ice monitoring and prediction and commercial navigation. Affected by the melting of the sea-ice surface, the accuracy and spatial coverage of the sea-ice velocity (SIV) retrieved by brightness temperature (TB) during the melting period are always lower than in winter. Our research indicates that the lack of ice–water discrimination in summer for the Advanced Microwave Scanning Radiometer 2 (AMSR2) 36 GHz TB is the main reason for the poor quality of its SIV results. We propose a new SIV retrieval scheme based on the polarization difference (P) of the 36 GHz TB. The 36-P SIV has a higher spatial coverage than that derived from 18-H, 36-H and 36-V SIVs and a higher maximum cross-correlation coefficient than 36 GH TB-derived SIVs. Compared with buoy and Synthetic Aperture Radar SIVs, the 36-P SIV’s error is close to that of 18-H SIV and significantly lower than that of 36 TB SIV. Therefore, our results indicate that 36-P is more competitive than the 36 GHz TB in SIV retrieval in summer. Further analysis shows that our proposed scheme is compatible with the two current mainstream SIV tracking algorithms, demonstrating its great potential for future summer SIV retrieval.

Bioimpedance analysis (BIA)–body composition monitoring (BCM) has been used to evaluate the hydration and nutritional status of adults and children on dialysis. However, its clinical application still has challenges, so further exploration is valuable. We used BIA-BCM to evaluate the hydration and nutritional status of children undergoing chronic peritoneal dialysis from 1 July 2021 to 31 December 2022 in the Children’s Hospital of Fudan University to explore the clinical value of this method. A total of 84 children on chronic peritoneal dialysis (PD) were included. In the PD group, 16 (19.05%) and 31 (36.90%) had mild and severe overhydration (OH), respectively; 41.27% (26/63) had a low lean tissue index (LTI). In the PD group, patients with relative OH (Re-OH) > 5.6% had significantly higher systolic blood pressure (SBP) and SBP z score (SBPz). Patients with LTI > 12% had significantly higher body mass index (BMI) and BMI z score (BMIz). Canonical correlation analysis indicated a linear relationship (ρ = 0.708) between BIA-BCM hydration and the clinical hydration indicator and a linear relationship (ρ = 0.995) between the BIA-BCM nutritional indicator and the clinical nutritional indicator. A total of 56% of children on chronic peritoneal dialysis had OH, and 41% had a low LTI. In PD patients, SBP and SBPz were correlated with BIA-BCM Re-OH, and BMI and BMIz were correlated with BIA-BCM LTI. BIA-BCM indicators have good clinical value in evaluating hydration and nutrition.

Color is an essential element in the exhibition space of museums, influencing people’s visual experience. To quantitatively study the relationship between color and individual visual perception in museum exhibition spaces, the study used eye-tracking technology combined with a questionnaire, exploring the relationship between color and visual perception in the exhibition environments of history museums in terms of hue, saturation, and brightness of color. Taking the Ruijin Central Revolutionary Base in Jiangxi Province as a historical display space for research, the results show that when the saturation is 69–77%, or the hue is red (0°H), the exhibited. environments have stronger color attractiveness. The study demonstrated that the first fixation duration in eye movement data significantly negatively correlates with the subject’s personal preference, comfort, pleasure, and attractiveness. Researchers can use this as an evaluation parameter for visual perception of exhibition space.

Shaofu Zhuyu decoction has been widely used to treat gynecological diseases; however, its mechanism of action in endometriosis remains unclear. We analyzed Shaofu Zhuyu decoction's chemical composition using ultra-high performance liquid chromatography-mass spectrometry. In an endometriosis mouse model, ectopic lesions weight measurements and hematoxylin and eosin staining were used to assess the therapeutic efficacy of Shaofu Zhuyu decoction. Effects on intestinal microflora were analyzed using 16S ribosomal ribonucleic acid sequencing, and impacts on focal fibrosis were analyzed using Masson's trichrome staining. Moreover, fibrosis- and metabolism-related proteins were assessed using immunohistochemistry and enzyme-linked immunosorbent assay. The study identified 157 chemical constituents within Shaofu Zhuyu decoction. Shaofu Zhuyu decoction treatment in mice with endometriosis resulted in a reduction in ectopic lesions weight (P

This study aims to estimate the impact of crude oil price on the DSEX broad index of the Dhaka stock exchange using the Vector Error Correction Model (VECM) for the study period 2013:01-2022:12. It has decomposed the oil price shock into supply side and demand side oil shock. The empirical result shows that the stock price decreases significantly with crude oil prices driven by the shock in oil production. In contrast, the improvement in global economic activity results in a shock in the oil price which has a significant positive impact on the stock price. Furthermore, the accumulated shock in oil prices has a significant positive impact on stock prices. The variance decomposition under the VEC model shows that the demand shock of oil price contributes more to the variation in stock price for the oil-importing country Bangladesh. Since different oil price shocks have different impacts, the policy maker and investors implement decisions based on the understating of the sources of the shocks.

Ovarian cancer (OC) is one of the deadliest gynecological malignancies in the world and is the leading cause of cancer-related death in women. The complexity and difficult-to-treat nature of OC pose a huge challenge to the treatment of the disease, Therefore, it is critical to find green and sustainable drug treatment options. Natural drugs have wide sources, many targets, and high safety, and are currently recognized as ideal drugs for tumor treatment, has previously been found to have a good effect on controlling tumor progression and reducing the burden of metastasis. However, its clinical transformation is often hindered by structural stability, bioavailability, and bioactivity. Emerging technologies for the treatment of OC, such as photodynamic therapy, immunotherapy, targeted therapy, gene therapy, molecular therapy, and nanotherapy, are developing rapidly, particularly, nanotechnology can play a bridging role between different therapies, synergistically drive the complementary role of differentiated treatment schemes, and has a wide range of clinical application prospects. In this review, nanoscale natural drug delivery systems (NNDDS) for targeted drug delivery against OC were extensively explored. We reviewed the mechanism of action of natural drugs against OC, reviewed the morphological composition and delivery potential of drug nanocarriers based on the application of nanotechnology in the treatment of OC, and discussed the limitations of current NNDDS research. After elucidating these problems, it will provide a theoretical basis for future exploration of novel NNDDS for anti-OC therapy.

Background Several previous cross‐sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle‐aged and older Chinese people in a longitudinal cohort. Methods and Results A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group‐based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low‐stable BRI trajectory, moderate‐stable BRI trajectory and high‐stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low‐stable BRI trajectory group, those in the moderate‐stable and high‐stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09–1.37) and 1.55 (95% CI, 1.26–1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P

Abstract Background The skeletal muscle growth rate and body size of Tibetan pigs (TIB) are lower than Large white pigs (LW). However, the underlying genetic basis attributing to these differences remains uncertain. To address this knowledge gap, the present study employed whole-genome sequencing of TIB (slow growth) and LW (fast growth) individuals, and integrated with existing NCBI sequencing datasets of TIB and LW individuals, enabling the identification of a comprehensive set of genetic variations for each breed. The specific and predominant SNPs in the TIB and LW populations were detected by using a cutoff value of 0.50 for SNP allele frequency and absolute allele frequency differences (△AF) between the TIB and LW populations. Results A total of 21,767,938 SNPs were retrieved from 44 TIB and 29 LW genomes. The analysis detected 2,893,106 (13.29%) and 813,310 (3.74%) specific and predominant SNPs in the TIB and LW populations, and annotated to 24,560 genes. Further GO analysis revealed 291 genes involved in biological processes related to striated and/or skeletal muscle differentiation, proliferation, hypertrophy, regulation of striated muscle cell differentiation and proliferation, and myoblast differentiation and fusion. These 291 genes included crucial regulators of muscle cell determination, proliferation, differentiation, and hypertrophy, such as members of the Myogenic regulatory factors (MRF) (MYOD, MYF5, MYOG, MYF6) and Myocyte enhancer factor 2 (MEF2) (MEF2A, MEF2C, MEF2D) families, as well as muscle growth inhibitors (MSTN, ACVR1, and SMAD1); KEGG pathway analysis revealed 106 and 20 genes were found in muscle growth related positive and negative regulatory signaling pathways. Notably, genes critical for protein synthesis, such as MTOR, IGF1, IGF1R, IRS1, INSR, and RPS6KA6, were implicated in these pathways. Conclusion This study employed an effective methodology to rigorously identify the potential genes associated with skeletal muscle development. A substantial number of SNPs and genes that potentially play roles in the divergence observed in skeletal muscle growth between the TIB and LW breeds were identified. These findings offer valuable insights into the genetic underpinnings of skeletal muscle development and present opportunities for enhancing meat production through pig breeding.

Flexible damping technology considering aseismic materials and aseismic structures seems be a good solution for engineering structures. In this study, a constrained damping structure for underground tunnel lining, using a rubber-sand-concrete (RSC) as the aseismic material, is proposed. The aseismic performances of constrained damping structure were investigated by a series of hammer impact tests. The damping layer thickness and shape effects on the aseismic performance such as effective duration and acceleration amplitude of time-domain analysis, composite loss factor and damping ratio of the transfer function analysis, and total vibration level of octave spectrum analysis were discussed. The hammer impact tests revealed that the relationship between the aseismic performance and damping layer thickness was not linear, and that the hollow damping layer had a better aseismic performance than the flat damping layer one. The aseismic performances of constrained damping structure under different seismicity magnitudes and geological conditions were investigated. The effects of the peak ground acceleration (PGA) and tunnel overburden depth on the aseismic performances such as the maximum principal stress and equivalent plastic strain (PEEQ) were discussed. The numerical results show the constrained damping structure proposed in this paper has a good aseismic performance, with PGA in the range (0.2–1.2)g and tunnel overburden depth in the range of 0–300 m.

Abstract This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18–83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24–28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (β = 0.67, 95% CI 0.35–0.98, P

Abstract Background Mucosal-associated invariant T (MAIT) cells have been reported to regulate tumor immunity. However, the immune characteristics of MAIT cells in non-small cell lung cancer (NSCLC) and their correlation with the treatment efficacy of immune checkpoint inhibitors (ICIs) remain unclear. Patients and methods In this study, we performed single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence assays to determine the proportion and characteristics of CD8+MAIT cells in patients with metastatic NSCLC who did and did not respond to anti-PD-1 therapy. Survival analyses were employed to determine the effects of MAIT proportion and C-X-C chemokine receptor 6 (CXCR6) expression on the prognosis of patients with advanced NSCLC. Results The proportion of activated and proliferating CD8+MAIT cells were significantly higher in responders-derived peripheral blood mononuclear cells (PBMCs) and lung tissues before anti-PD-1 therapy, with enhanced expression of cytotoxicity-related genes including CCL4, KLRG1, PRF1, NCR3, NKG7, GZMB, and KLRK1. The responders’ peripheral and tumor-infiltrating CD8+MAIT cells showed an upregulated CXCR6 expression. Similarly, CXCR6+CD8+MAIT cells from responders showed higher expression of cytotoxicity-related genes, such as CST7, GNLY, KLRG1, NKG7, and PRF1. Patients with ≥15.1% CD8+MAIT cells to CD8+T cells ratio and ≥35.9% CXCR6+CD8+MAIT cells to CD8+MAIT cells ratio in peripheral blood showed better progression-free survival (PFS) after immunotherapy. The role of CD8+MAIT cells in lung cancer immunotherapy was potentially mediated by classical/non-classical monocytes through the CXCL16-CXCR6 axis. Conclusion CD8+MAIT cells are a potential predictive biomarker for patients with NSCLC responding to anti-PD-1 therapy. The correlation between CD8+MAIT cells and immunotherapy sensitivity may be ascribed to high CXCR6 expression.

Spatial-temporal dynamics monitoring of Arctic vegetation structure (i.e. distribution range of tundra and forest) is of great significance for evaluating global warming effect. Currently, time-series monitoring of Arctic vegetation structure relies primarily on the Normalized Difference Vegetation Index (NDVI), which is derived from optical remote sensing images. However, because of factors such as the long revisit period of satellites and the impact of climate, optical observations are severely lacking in the Arctic region. This results in NDVI time-series data highly discontinuous and difficult to reflect actual variations in Arctic vegetation structure, and the traditional time-series reconstruction method would usually fail for severe missing conditions. Therefore, this study developed a Time Series Reconstruction method considering Periodic Trend (TSR-PT), which is specifically for alleviating the severe missing observation condition in the Arctic region. It can separate the phenological change and trend change of the incomplete time series NDVI, and borrow the information from the neighboring unchanged years for compensate of the missing observations in current years, based on the learned inter-annual and intra-annual correlation. We explore its usability in monitoring vegetation structure variation in Vorkuta region (transition zone of tundra and taiga in the Arctic Circle) based on MODIS data. It is found that the proposed TSR-PT is able to reconstruct NDVI with reasonable phenological feature even the missing rate reaches over 70%, which is usually falsely constructed by traditional filtering or fitting method, and suppress them by 0.038 in terms of RMSE; besides, we find that since 21-century, the Arctic trees have continued to increase and encroach the original tundra ecosystem, which caused a largely Arctic vegetation structural change, and we believe the proposed method would largely promote the Arctic vegetation research.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract Background Anesthesia for spinal muscular atrophy (SMA) patients undergoing spinal deformity surgery is challenging. We report an unusual case of an SMA girl who developed severe intraoperative hypoxemia and hypotension during posterior spinal fusion related with surgical positioning. Case presentation A 13-yr-old girl diagnosed with SMA type 2, severe kyphoscoliosis and thoracic deformity was scheduled for elective posterior spinal fusion. She developed severe hypoxemia and profound hypotension intraoperatively in the prone position with surgical table tilted 45° to the right. Though transesophageal echocardiography (TEE) could not be performed due to limited mouth opening, her preoperative computed tomography revealed a severely distorted thoracic cavity with much reduced volume of the right side. A reasonable explanation was when the surgeons performed surgical procedure with the tilted surgical table, the pressure was directly put on the shortest diameter of the significantly deformed thoracic cavity, causing severe compression of the pulmonary artery, resulting in both hypoxemia and hypotension. The patient stabilized when the surgical table was tilted back and successfully went through the surgery in the leveled prone position. Conclusions Spinal fusion surgery is beneficial for SMA patients in preventing scoliosis progression and improving ventilation. However, severe scoliosis and thoracic deformities put them at risk of both hemodynamic and respiratory instability during surgical positioning. When advanced monitoring like TEE is not practical intraoperatively, preoperative imaging may help with differential diagnosis, and guide the surgical positioning to minimize mechanical compression of the thoracic cavity, thereby helping the patient complete the surgery safely.

Esophageal cancer (EC), a common type of malignant tumor, ranks as the sixth highest contributor to cancer-related mortality worldwide. Due to the condition that most patients with EC are diagnosed at advanced or metastatic status, the efficacy of conventional treatments including surgery, chemotherapy and radiotherapy is limited, resulting in a dismal 5-year overall survival rate. In recent years, the application of immune checkpoint inhibitors (ICIs) has presented a novel therapeutic avenue for EC patients. Both ICIs monotherapy and immunotherapy combined with chemotherapy or chemoradiotherapy (CRT) have demonstrated marked benefits for patients with advanced EC. Adjuvant or neoadjuvant therapy incorporating immunotherapy has also demonstrated promising prospects in the context of perioperative treatment. Nonetheless, due to the variable response observed among patients undergoing immunotherapy, it is of vital importance to identify predictive biomarkers for patient stratification, to facilitate identification of subgroups who may derive greater benefits from immunotherapy. In this review, we summarize validated or potential biomarkers for immunotherapy in EC in three dimensions: tumor-cell-associated biomarkers, tumor-immune microenvironment (TIME)-associated factors, and host-associated biomarkers, so as to provide a theoretical foundation to inform tailored therapy for individuals diagnosed with EC.

Summary: Background: This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small–cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Methods: Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4–6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m2, D1-3, Q3W and cisplatin, 75 mg/m2, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30 Gy in 10 fractions or ≥50 Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. Findings: From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2–not reached months) and 10.1 months (95% CI: 6.9–15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3–82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7–95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P = 0.071; ctDNA, P = 0.060) and OS (tissue, P = 0.032; ctDNA, P = 0.031). Interpretation: Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. Funding: This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P

Background: The Chinese herbal compound Lian-Gui-Ning-Xin-Tang (LGNXT), composed of 9 herbs, has a significant antiarrhythmic effect. Previous studies have confirmed that preventing intracellular Ca2+ overload and maintaining intracellular Ca2+ homeostasis may be the important antiarrhythmic mechanisms of LGNXT. Recent studies are focused on elucidating the mechanisms and pharmacodynamic substances of LGNXT. Purpose: 1) To investigate the antiarrhythmic mechanisms of LGNXT; 2) to explore the association of pharmacodynamics (PD) and pharmacokinetics (PK) of the potential pharmacodynamic substances in LGNXT to further verify the mechanisms of action. Methods: First, pharmacodynamic studies were conducted to determine the effect of LGNXT in arrhythmia at the electrophysiological, molecular, and tissue levels, and the “effect–time” relationship of LGNXT was further proposed. Next, an HPLC-MS/MS method was established to identify the “dose–time” relationship of the 9 potential compounds. Combining the “effect–time” and “dose–time” curves, the active ingredients closely related to the inhibition of inflammation, oxidative stress, and energy metabolism were identified to further verify the mechanisms and pharmacodynamic substances of LGNXT. Results: Pretreatment with LGNXT could delay the occurrence of arrhythmias and reduce their duration and severity. LGNXT exerted antiarrhythmic effects by inhibiting MDA, LPO, IL-6, and cAMP; restoring Cx43 coupling function; and upregulating SOD, Ca2+-ATPase, and Na+-K+-ATPase levels. PK-PD association showed that nobiletin, methylophiopogonanone A, trigonelline, cinnamic acid, liquiritin, dehydropolisic acid, berberine, and puerarin were the main pharmacodynamic substances responsible for inhibiting the inflammatory response in arrhythmia. Methylophiopogonanone A, dehydropalingic acid, nobiletin, trigonelline, berberine, and puerarin in LGNXT exerted antiarrhythmic effects by inhibiting oxidative stress. Dehydropalingic acid, berberine, cinnamic acid, liquiritin, puerarin, trigonelline, methylophiopogonanone A, nobiletin, and tetrahydropalmatine exerted antiarrhythmic effects by inhibiting the energy-metabolism process. Conclusions: LGNXT had a positive intervention effect on arrhythmias, especially ventricular tachyarrhythmias, which could inhibit inflammation, oxidative stress, and energy metabolism; positively stabilize the structure, and remodify the function of myocardial cell membranes. Additionally, the PD–PK association study revealed that methylophiopogonanone A, berberine, trigonelline, liquiritin, puerarin, tetrahydropalmatine, nobiletin, dehydropachymic acid, and cinnamic acid directly targeted inflammation, oxidative stress, and energy metabolism, which could be considered the pharmacodynamic substances of LGNXT. Thus, the antiarrhythmic mechanisms of LGNXT were further elucidated.

BackgroundWith the advent of electronic nicotine delivery systems, the use of nicotine and tobacco products (NTPs) among adolescents and young adults remains high in the US. Use of e-cigarettes additionally elevates the risk of problematic use of other substances like cannabis, which is often co-used with NTPs. However, their effects on brain health, particularly the hippocampus, and cognition during this neurodevelopmental period are poorly understood.MethodsHealthy late adolescents/young adults (N = 223) ages 16–22 completed a structural MRI to examine right and left hippocampal volumes. Memory was assessed with the NIH Toolbox Picture Sequence Memory Test (PSMT) and Rey Auditory Verbal Learning Test (RAVLT). Cumulative 6-month NTP and cannabis episodes were assessed and modeled continuously on hippocampal volumes. Participants were then grouped based on 6-month NTP use to examine relationships with the hippocampus and memory: current users (CU) endorsed weekly or greater use; light/abstinent users (LU) endorsed less than weekly; and never users (NU).ResultsNTP use predicted larger hippocampal volumes bilaterally while cannabis use had no impact nor interacted with NTP use. For memory, larger left hippocampal volumes were positively associated with PSMT performance, RAVLT total learning, short delay and long delay recall for the NU group. In contrast, there was a negative relationship between hippocampal volumes and performances for LU and CU groups. No differences were detected between NTP-using groups.ConclusionThese results suggest that the hippocampus is sensitive to NTP exposure during late adolescence/young adulthood and may alter typical hippocampal morphometry in addition to brain-behavior relationships underlying learning and memory processes.

Objective: To characterize the clinical and imaging features of circumscribed choroidal hemangioma (CCH), and to evaluate individualized treatment efficiency of photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or their combination, followed by retrobulbar injection of betamethasone on CCH resolvement. Methods: Forty-nine patients with CCHs who underwent PDT, TTT or PDT+TTT treatments were retrospectively analyzed. Their treatment efficacy was compared by analyzing the change of best corrected visual acuity (BCVA), subretinal fluid (SRF) and CCH lesion characteristics. Results: PDT, TTT and PDT+TTT were respectively administrated in 17, 11 and 21 patients. No significant difference in age, gender, affected eyes and tumor location across the three groups. Baseline BCVA were 0.41 ± 0.28, 0.62 ± 0.30 and 0.24 ± 0.24 for PDT, TTT and PDT+TTT groups, respectively (F = 6.572, P = 0.003). CCH treated by three strategies showed significant difference in maximum tumor basal diameter, SRF areas and macula involvement prior to the treatment (P < 0.05). Patients receiving PDT+TTT exhibited larger tumor basal diameter, more SRF, higher ratio of macular involvement than other groups. A total of 38 (77.6 %) cases had good visual acidity with final BCVA ≥0.5 after treatments. PDT and PDT+TTT treatment groups acquired more vision improvement (0.27 ± 0.23 and 0.31 ± 0.26) in BCVA than TTT group (0.09 ± 0.13). All SRF were resolved within two weeks of treatment and no recurrent SRF were found. Conclusion: The three treatments showed good performance in improving visual function and controlling SRF, and individualized treatment should be selected primarily by the tumor location, and then the tumor size and presence of SRF.

Social media now has emerged as one of the most widely used communication channels. The objective of this work is to verify the factors that influence the compulsive use of TikTok, as well as the mediating role of algorithm awareness, and to identify the predictors of well-being related to the use of TikTok. In the present work, the relevance of the study of PSRs and FoMO that affect the compulsive use of TikTok in young people is discussed. A total of 379 young university students (56.7 % girls) between 15 and 25 years old (M = 19.80; S.D. = 1.49) were surveyed using self-reports. Data treatment followed serial mediation through structural equation modeling. The results showed that exist significant relationships between these variables. Likewise, they reinforce the understanding of the diversity of the mechanisms of social and parasocial motivations on compulsive use and well-being. The results highlight the need to strengthen the training and education of young people in the appropriate and regulated use of TikTok in the university setting.

Background: The morphology of proximal humeral fractures (PHFs) is complex, and the fixation and selection of implants need to be guided by the fracture type and classification, which requires an accurate understanding of the fracture line. This study had three purposes. 1) Define and analyze the fracture lines and morphological features of all types PHFs by three-dimensional (3D) mapping technology. 2) Determine the osteotomy position of the biomechanical model of the PHFs according to the fracture heat map. 3) Based on the analysis of the pathological morphology and distribution of a large number of consecutive cases of PHFs, propose a novel classification of PHFs.Methods: We retrospectively collected 220 cases of PHFs and generated a 3D fracture map and heat map based on computed tomography (CT) imaging. Through analysis of the fracture morphology of the 220 PHFs, a novel classification was proposed. The primary criterion for staging was the continuity between the humeral head and the greater tuberosity and lesser tuberosity, and the secondary criterion was the relationship between the humeral head segment and the humeral shaft.Results: The fracture line was primarily found around the metaphyseal zone of region of the surgical neck, with the most extensive distribution being below the larger tuberosity and on the posterior medial side of the epiphysis. We suggest that the osteotomy gap should be immediately (approximately 5–10 mm) below the lower edge of the articular surface. The most common type of fracture was type I3 (33 cases, 15.0%), followed by type IV3 fracture (23 cases, 10.4%), and type III2 fracture (22 cases, 10.0%). Interobserver and intraobserver reliability analysis for the fracture classification revealed a k value (95% confidence interval) of 0.639 (0.57–0.71) and 0.841, P < 0.01, respectively.Conclusion: In this study, the fracture line and morphological characteristics of PHFs were clarified in detail by 3D mapping technique. In addition, a new classification method was proposed by analysis of the morphological characteristics of 220 PHFs, A two-part fracture model for PHFs is also proposed.

BackgroundAeromonas dhakensis is associated with soft tissue infection, bacteremia and gastroenteritis. Involvement of respiratory system in adults is extremely rare. We report a case of fulminant pneumonia and bacteremia due to A. dhakensis in a patient without underlying diseases.Case presentationA 26-year-old man became ill suddenly with pneumonia after swimming in a river. Despite intensive support measures in the intensive care unit, he died 13 hours after admission and 4 days after his first symptoms. Autopsy showed abundant Gram-negative bacteria, massive inflammatory cell infiltration, edema, necrosis and hemorrhage in lung tissue. A. dhakensis was isolated from blood culture taken at admission and bronchoalveolar lavage fluid (BALF) after intubation. Moreover, A. dhakensis was also detected in lung tissue by metagenomic next-generation sequencing (mNGS) assay. The infection may have come from river water.ConclusionIn patients who develop a fulminant pneumonia after contacting an aquatic environment, A. dhakensis should be alerted and mNGS may aid in the detection of aquatic pathogens by being more sensitive and specific versus traditional bacterial culture.

Proximal humerus fractures (PHFs) are common in the elderly and usually involve defects in the medial column.The current standard for medial column reconstruction is a lateral locking plate (LLP) in combination with either an intramedullary fibula support or an autogenous fibula graft. However, autogenous fibula graft can lead to additional trauma for patients and allogeneic fibular graft can increase patients’ economic burden and pose risks of infection and disease transmission. The primary objective of this study was to introduce and assess a novel “Sandwich” fixation technique and compare its biomechanical properties to the traditional fixation methods for PHFs. In this study, we established finite element models of two different internal fixation methods: LLP-intramedullary reconstruction plate with bone cement (LLP-IRPBC) and LLP-intramedullary fibula segment (LLP-IFS). The biomechanical properties of the two fixation methods were evaluated by applying axial, adduction, abduction, torsional loads and screw extraction tests to the models. These FEA results were subsequently validated through a series of biomechanical experiments. Under various loading conditions such as axial, adduction, abduction, and rotation, the LLP-IRPBC group consistently demonstrated higher structural stiffness and less displacement compared to the LLP-IFS group, regardless of whether the bone was in a normal (Nor) or osteoporotic (Ost) state. Under axial, abduction and torsional loads, the maximum stress on LLPs of LLP-IRPBC group was lower than that of LLP-IFS group, while under adduction load, the maximum stress on LLPs of LLP-IRPBC group was higher than that of LLP-IFS group under Ost condition, and almost the same under Nor condition. The screw-pulling force in the LLP-IRPBC group was 1.85 times greater than that of the LLP-IFS group in Nor conditions and 1.36 times greater in Ost conditions. Importantly, the results of the biomechanical experiments closely mirrored those obtained through FEA, confirming the accuracy and reliability of FEA. The novel “Sandwich” fixation technique appears to offer stable medial support and rotational stability while significantly enhancing the strength of the fixation screws. This innovative approach represents a promising strategy for clinical treatment of PHFs.

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10−5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Abstract Background For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16–26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. Trial registration ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Recent building-oriented change detection studies considered only morphological changes in buildings, and few publicly available change detection datasets further distinguish among building types. In this study, we propose a semantic change detection network named BSCDNet that considers both morphological and semantic changes in buildings. BSCDNet adopts a multitasking branch structure with object classification, change detection, and segmentation to simultaneously achieve object-level semantic classification and change analysis of buildings in bitemporal, high-spatial-resolution (HSR) imagery. In the object classification branch, a graph attention network is utilized to capture the spatial and semantic correlations among buildings during classification. The change detection branch applies both spatial and channel attention mechanisms to eliminate nonbuilding interference and enhance change features. Moreover, the segmentation branch adopts a distinctive instance segmentation procedure that improves the accuracy of object segmentation. We created a building change detection dataset with category differentiation based on HSR imagery to validate the proposed method. Ablation experiments verify the effectiveness and advantages of the above-mentioned task branches. Furthermore, in comparative experiments with several SOTA semantic change detection methods such as HRSCD, SCDNet, and MR_CD, BSCDNet reached the optimal level in terms of F1 and mIoU when evaluating the change detection performance, as well as kappa and score for evaluating the classification performance.

Urban renewal has led to the proliferation of informal urban habitats, such as slums, shanty towns, and urban villages (UVs). As an important component of urban renewal, UVs influence urban spatial structure and land use patterns. Therefore, the fine extraction of UV is of great theoretical and practical significance. Existing UV classification techniques mostly employ machine learning and convolutional neural network based models, which struggle to perceive long-range global semantic information. In this article, based on high-resolution remote sensing images, we propose a multiscale mask transformer model for UV (MaskUV). It can extract both local texture features and global features. The multiscale mask transformer module with mask attention can aggregate different levels of pixel and object features, enhancing the model's recognition and generalization abilities. We extracted UV in seven cities in the Pearl River Delta (PRD) using MaskUV and analyzed the spatial pattern and accessibility of UV. Due to the scarcity of fine-grained UV detection datasets, we also provide a novel dataset (UVSet) containing 3415 pairs of 512 × 512 high-resolution UV images and labels, with a spatial resolution of 1 m. Comparative experiments with several UV extraction models demonstrate the effectiveness of MaskUV, achieving an F1 score of 84.39% and an IoU of 73.00% on UVSet. Besides, MaskUV achieves highly accurate detection results in seven cities in the PRD, with average F1 and IoU values of 84.41% and 72.44%, respectively.

Building height dataset is crucial in urban studies, holding significant importance in understanding the interactions of human activities and the built-up environment. However, high-resolution three-dimensional building datasets covering large areas are limited. A rapid and accurate method for revealing fine-scale urban morphology is required. In this study, we developed a method for estimating building heights at the building scale. First, we integrated multisource datasets (i.e., synthetic aperture radar, optical, terrain, social-economic, and vector-based datasets) and built the machine learning model for building height estimation. Second, we applied the model to 11 cities in the U.S. and assessed its performance. Our results were consistent with the reference data, indicating that the effectiveness of our method is applicable [i.e., the R2 was 0.82, and the root mean square error (RMSE) was 3.39 m]. The evaluated results in various cities, across different height intervals, and within distinct regions also show the good agreement with reference heights according to the correlation (R2: 0.51–0.86, RMSE: 2.57–5.97 m in cities) and similar height distribution. Moreover, our results also showed the superiority by comparing with other height datasets at different scales. Finally, we mapped the building-scale height to characterize the urban morphology. These results demonstrate our proposed method's usable accuracy and the vast application potential in estimating building heights. Our proposed method's refined building height information can significantly help socioeconomic and climatological urban studies.

Individual tree segmentation (ITS) is a pivotal technique in orchard research, estimating tree counts and delineating crown contours. This method provides foundational data for assessing orchard health, nutritional composition, and predicting yield. Unmanned aerial vehicles (UAVs) have become an essential data source for (ITS) due to their capability to capture ultra-fine details. However, current deep-learning-based ITS methods struggle to accurately handle densely overlapping fruit tree distributions with similar characteristics in UAVs images, primarily due to the intricate nature of spatial arrangements in such scenarios. In this article, we propose CEDAnet, a context enhancement, and density adjustment network, to address the challenge of dense fruit trees segmentation. Specifically, a transformer-based contextual aggregation module is designed to distinguish different instances and refine the boundary of the instances. We have proposed a density-guided nonmaximum suppression method to adaptively generate sufficient candidate bounding boxes, aiming to retain more potential instances in dense trees. To evaluate the effectiveness and robustness of our proposal, we curated two ITS datasets constructed with imagery captured by UAVs, namely instance segmentation in Conghua images dataset (iSCHID) and instance segmentation in Maoming images dataset (iSMMID) based on their respective spatial characteristics. Experimental results on both two datasets demonstrated that CEDAnet yields competitive results in ITS tasks, with the bounding box AP of 0.498, segmentation AP of 0.493 in iSCHID, and the bounding box AP of 0.706, segmentation AP of 0.703 in iSMMID.