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Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract Background Computed tomography (CT) is widely in clinics and is affected by metal implants. Metal segmentation is crucial for metal artifact correction, and the common threshold method often fails to accurately segment metals. Purpose This study aims to segment metal implants in CT images using a diffusion model and further validate it with clinical artifact images and phantom images of known size. Methods A retrospective study was conducted on 100 patients who received radiation therapy without metal artifacts, and simulated artifact data were generated using publicly available mask data. The study utilized 11,280 slices for training and verification, and 2,820 slices for testing. Metal mask segmentation was performed using DiffSeg, a diffusion model incorporating conditional dynamic coding and a global frequency parser (GFParser). Conditional dynamic coding fuses the current segmentation mask and prior images at multiple scales, while GFParser helps eliminate high-frequency noise in the mask. Clinical artifact images and phantom images are also used for model validation. Results Compared with the ground truth, the accuracy of DiffSeg for metal segmentation of simulated data was 97.89% and that of DSC was 95.45%. The mask shape obtained by threshold segmentation covered the ground truth and DSCs were 82.92% and 84.19% for threshold segmentation based on 2500 HU and 3000 HU. Evaluation metrics and visualization results show that DiffSeg performs better than other classical deep learning networks, especially for clinical CT, artifact data, and phantom data. Conclusion DiffSeg efficiently and robustly segments metal masks in artifact data with conditional dynamic coding and GFParser. Future work will involve embedding the metal segmentation model in metal artifact reduction to improve the reduction effect.

Abstract Background PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method. Methods We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality. Results The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P

Abstract Objective The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of β-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. Methods From our initial sample of 52 patients, we observed 48 patients with β-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. Results The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with βCD41-42/βCD17 and 6 cases with βCD41-42/β-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P

To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007–2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

Abstract Background Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. Methods Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. Results The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. Conclusions The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery. Graphical Abstract

Abstract Electrochemical uranium extraction from nuclear wastewater represents an emerging strategy for recycling uranium resources. However, in nuclear fuel production which generates the majority of uranium-containing nuclear wastewater, fluoride ion (F−) co-exists with uranyl (UO2 2+), resulting in the complex species of UO2Fx and thus decreasing extraction efficiency. Herein, we construct Tiδ+-PO4 3− ion pair extraction sites in Ti(OH)PO4 for efficient electrochemical uranium extraction in wastewater from nuclear fuel production. These sites selectively bind with UO2Fx through the combined Ti-F and multiple O-U-O bonds. In the uranium extraction, the uranium species undergo a crystalline transition from U3O7 to K3UO2F5. In real nuclear wastewater, the uranium is electrochemically extracted with a high efficiency of 99.6% and finally purified as uranium oxide powder, corresponding to an extraction capacity of 6829 mg g−1 without saturation. This work paves an efficient way for electrochemical uranium recycling in real wastewater of nuclear production.

At present, the detection of mining subsidence basins by interferometric synthetic aperture radar (InSAR) mainly relies on underground mining data or human visual interpretation. To solve this problem, this paper proposes a deformation basin detection network (DBD-Net) for large-scale InSAR interferograms. At the same time, in order to train the network, a sample database of mining subsidence basins is established by using real differential interferogram data and simulated interferogram data. In Shendong Mining Area and Yanzhou Mining Area, three differential interference images with different time baselines were selected to verify the network performance. The results show that the detection accuracy of deformation basin detection network (DBD-Net) in large-scale InSAR interferograms for mining subsidence basins is 81.87%. Most of the missed and false detection areas are areas with serious noise pollution and unclear characteristics.

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%–47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46–2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16–2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03–1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17–1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58–4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42–0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

ABSTRACT: Globally, China is one of the primary citrus producers. This study provided a theoretical reference for sustainable production in the citrus industry in China by measuring citrus production efficiency under non-point source pollution and analyzing inter-provincial variability. In this study, non-radio logical and non-angled data envelopment analysis models were used in seven provinces during 2006-2018 based on non-desired outputs. The temporal and spatial characteristics were analyzed to determine the factors that cause efficiency losses. Results indicated that the citrus production efficiency had a general w-type trend with high inter-provincial variability, where the highest and lowest production efficiencies occurred in Hubei Province and Guangdong Province, respectively. In the past four years, a redundancy in labor and fertilizer inputs was also observed in Guangdong and Fujian, respectively. The shrinkable proportion of each factor input in the seven provinces was zero. An increase in citrus yield per hectare was recorded, in which the highest was in Guangdong. In each province, high emissions of total nitrogen and phosphorus generally caused the decrease in citrus production efficiency.

Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Hydrogenation and fluorination is a significant method to tune the electronic properties of two-dimensional (2D) materials. This paper theoretically predicted and analyzed the effects and regulatory mechanisms of surface functionalization on the electronic properties of 2D semiconductor tetrahex Boron/Aluminium Nitride (th-BN/th-AlN). The density-functional theory (DFT) calculations were employed to study various trends of band structure, effective mass, and work function. The results show that the electronic properties of 2D th-BN/th-AlN are susceptible to the surface adsorption atom species and coverage. Interconversions between semiconductor and metal properties or indirect and direct band structures in 2D th-XN (X = B, Al) can be realized by hydrogen and fluorine surface adsorption. The band gap expands and the work function decreases after H atom is adsorbed on the surface, while the band gap first increases and then decreases and the work function expands after F is adsorbed on the surface. After functionalization, the effective mass of the hole will be reduced to even lighter than that of an electron in certain directions. The change mechanisms of electronic properties in th-BN/AlN is surface adsorbed atoms will cause sp2-hybridized atoms to turn into sp3-hybridized atoms, which leads to the polarized double bonds between adjacent atoms becoming a single σ bond. The chemical bond changing will result in the band near the Fermi level gradually disappearing.

Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP.Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses.Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers.Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.

Abstract Cervical cancer is a significant public health concern, particularly in low‐ and middle‐income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21–65 from three medical centers in Taiwan. The findings indicated that the self‐sampling kit was as effective as physician‐collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self‐sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self‐sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.

IntroductionFeeding bamboo powder is a kind of fiber raw material mainly composed of insoluble dietary fiber (IDF). In this study, IDF-based rice husk meal and feeding bamboo powder were used to compare the effects of bamboo fiber on fecal microflora and the performance of lactating sows and their offspring piglets.MethodsThirty healthy crossbred gilts (Yorkshire × Landrace) at day 105 of gestation were randomly allocated into three groups: CON, TRE1 supplemented with 2% BBF1 (feeding bamboo powder), and TRE2 supplemented with 2% BBF2 (99% feeding bamboo powder +1% bamboo fiber polymer material). The reproductive performance, serum indexes, and fecal microbiota of sows and piglets were analyzed. The results showed that, compared with CON, the average feed intake of sows in TRE1 during the second week of lactation was significantly increased by 21.96% (p

Summary: Biofilm formation plays a significant role in antibiotic resistance, necessitating the search for alternative therapies against biofilm-associated infections. This study demonstrates that 20 μg/mL tryptanthrin can hinder biofilm formation above 50% in various A. baumannii strains. Tryptanthrin impacts various stages of biofilm formation, including the inhibition of surface motility and eDNA release in A. baumannii, as well as an increase in its sensitivity to H202. RT-qPCR analysis reveals that tryptanthrin significantly decreases the expression of the following genes: abaI (19.07%), abaR (33.47%), bfmR (43.41%), csuA/B (64.16%), csuE (50.20%), ompA (67.93%), and katE (72.53%), which are related to biofilm formation and quorum sensing. Furthermore, tryptanthrin is relatively safe and can reduce the virulence of A. baumannii in a Galleria mellonella infection model. Overall, our study demonstrates the potential of tryptanthrin in controlling biofilm formation and virulence of A. baumannii by disrupting different stages of biofilm formation and intercellular signaling communication.

Urban green infrastructure (GI) addresses human social development issues and challenges through urban green space ecosystem services. However, the ecosystem service functions of suburban cropland, especially regulating services and cultural services, have been seriously underestimated. The distribution of green spaces and suburban cropland varies in different regions of China, as well as their potential development methods. This article examines the potential of integrating suburban cropland into urban green infrastructure, offering a perspective on nature-based solutions in China. We divided the suburban cropland in China into three parts: peri‑suburban, mid-suburban, and outer-suburban by the concept of 15-minute living circle based on different travel modes of people. Based on statistical yearbook data, satellite remote sensing images and the fragstats 4.2 programme, a quantitative analysis was conducted on the spatial distribution, landscape pattern and social development of suburban farmland and green space in four cities. Then, the potential for improving the exposure level of suburban cropland after incorporating suburban cropland into urban green infrastructure was quantified and compared. Finally, we explored the potential development of the three kinds of suburban cropland as green infrastructure based on the concept of NbS. We found the spatial pattern of cropland and green space in the mid-suburban is greatly affected by regional geographical conditions, the green exposure level, i.e., green space availability indicators, in Beijing, Shanghai, Guangzhou, and Xi'an increased by 83 %, 300 %, 24 %, and 612 %, respectively, after incorporating suburban cropland into urban green infrastructure. The potential development models for suburban cropland should be based on NbS and China's national conditions: peri‑suburban cropland should be fully utilized for cultural and social functions, the mid-suburban cropland should focus on multifunctional utilization of cropland, and the outer-suburban is prioritized for ecological functions. Our study provides scientific insights for deep exploration of the functions of suburban cropland in China.

Nature-based Solutions (NbS) is a concept aims to address challenges related to human well-being, including human health, socio-economic development, and ecological security on both national and global scales. This concept was proposed against the backdrop of global climate change, ecological crises affecting humanity, and threats to sustainable development and it has been increasingly recognized and applied internationally over the past decade. The principle of NbS is reciprocity between humans and ecosystems, which is completely in line with the goals, systems, practices, and concepts guiding China's construction of ecological civilization. This paper clarifies concepts, evaluation criteria, and comprehensive benefits related to NbS, to trace the connection between NbS and both traditional and contemporary ecological civilization principles in China. By drawing valuable experience from NbS practices in China, it will focus on proposing policy and implementation suggestions to address challenges currently faced in NbS applications in China. This research will promote the research and practice of nature-based solutions in China. Meanwhile, provide novel perspectives and technologies for urban ecological design as well as sustainable development.

Abstract Background Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. Results To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. Conclusions This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy. Graphical Abstract

Due to the potential for high energy harvesting capacity, subwavelength scale semiconductor nanostructured arrays are used to address the issue of single-junction thin-film solar cells' limited solar energy harvesting. Along with numerical simulations, an effective and efficient algorithm is crucial to maximizing the optical field modulation and energy trapping capacity of nanostructures. Based on the effective medium theory and the leaky mode resonance, an analytical feedback algorithm is suggested in this study to determine the precise the dimensions of vertically aligned InP stepped nanocylinders (SNCs) for maximum solar energy absorption. For both square and hexagonally arranged two-segment or three-segment InP SNC arrays, the ideal geometrical dimensions were quantitatively estimated for maximum energy harvesting. Densities of short-circuit current Jscs under the AM 1.5G spectrum's illumination as the measurement standard, they were computed for each SNC array. The maximal Jsc of 32.85 mA/cm2 was obtained with square three-segment InP SNC arrays. The optimized SNC arrays for the maximum light absorption are also validated and examined using thorough finite-difference time-domain computational simulations. The algorithm estimated maximum Jsc had tolerances of under 1.8% for all scenarios, which, when compared to simulations, shows that this analytical method offers a practical and efficient means to direct the design of high-performance InP SNC arrays solar cells.

Underground space creation and energy extraction, which induce unloading on rock fractures, commonly occur in various rock engineering projects, and rock engineering projects are subjected to high temperatures with increasing depth. Fluid flow behavior of rock fractures is a critical issue in many subsurface rock engineering projects. Previous studies have extensively considered permeability evolution in rock fractures under loading phase, whereas changes in fracture permeability under unloading phase have not been fully understood. To examine the unloading-induced changes in fracture permeability under different temperatures, we performed water flow-through tests on fractured rock samples subjected to decreasing confining pressures and different temperatures. The experimental results show that the permeability of fracture increases with unloading of confining pressure but decreases with loading-unloading cycles. Temperature may affect fracture permeability when it is higher than a certain threshold. An empirical model of fracture hydraulic aperture including two material parameters of initial normal stiffness and maximum normal closure can well describe the permeability changes in rough rock fracture subjected to loading-unloading cycles and heating. A coupled thermo-mechanical model considering asperity damage is finally used to understand the influences of stress paths and temperatures on fracture permeability.

Abstract This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab–chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA–IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9–81.0%). For patients with ctDNA– vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778).

In the long-term unattended condition, the continuous operation of bridge safety monitoring micro-system (BSMMS) in mountain areas has the issue of insufficient energy supply. Therefore, a photovoltaic-thermoelectric hybrid power generation system (PV-TEG) is proposed to power the temperature, wind speed, and tilt sensors of BSMMS. The power generation performance and characteristics of PV and TEG are experimentally investigated to find the operation mode to match the bridge monitoring. In addition, the intermittent operation mode of BSMMS is optimized to achieve longer running times. The experimental results show that the output voltage and power generation of the PV-TEG can meet the energy consumption demands of all sensors. TEG power generation is linear with bridge temperature, which can trigger TEG to support the temperature sensor operation. The energy storage battery supports the BSMMS to run for 8.99 days in the mode of running 5 min every 5-min intervals. Optimizing the operation time and interval of the BSMMS to run once in half an hour, it can run continuously for up to 17.97–22.46 days. This work provides a reference for the design of an unattended self-powered energy supply system for a multi-parameter integrated bridge safety monitoring system.

Infections caused by Pseudomonas aeruginosa biofilm significantly endanger human health worldwide. Biofilms are closely associated with antibiotic resistance because biofilms significantly undermine the efficacy of antibiotics. A novel ultrasound-launched targeted nanoparticle was developed to universally destroy biofilm, target bacteria, deliver antibiotics, and efficiently kill bacteria via ultrasonic cavitation and antibacterial sonodynamic therapy. The nanoparticle consisted of poly (lactic-co-glycolic acid) loading ciprofloxacin and perfluoropentane with a bacteria-targeted antibody installed on the nanoparticle for binding to specific bacteria. The nanoparticle exhibited a sensitive response to ultrasound and the rapid liquid-gas phase transition of perfluoropentane resulted in a cavitation effect that destroyed the extracellular polymeric substances of the biofilm and allowed deep penetration of the antibiotics. In addition, ciprofloxacin induced additional reactive oxygen species production under ultrasound stimulation, leading to an enhanced bactericidal effect and potent anti-infective activity in vivo. This study presents an effective strategy to tackle the extracellular polymeric substance barriers for overcoming antibiotic resistance and removing a biofilm.

ObjectiveTo observe the efficacy and safety of pelvic floor magnetic stimulation (PFMS) combined with mirabegron in female patients with refractory overactive bladder (OAB) symptoms.Patients and methodsA total of 160 female patients with refractory OAB symptoms were prospectively randomized into two groups. Eighty cases in the combination group accepted PFMS and mirabegron therapy and 80 cases as control only accepted mirabegron therapy (The clinical trial registry number: ChiCTR2200070171). The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQol), symptom bother score and OABSS between two groups were compared at the 1st, 2nd and 4th week ends.ResultsAll of 160 patients were randomly assigned to two groups, of which 80 patients were included in the combination group and 80 in the mirabegron group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week and the 4th week after combination treatment were significantly lower than those in the mirabegron group (p 0.05). With respect to secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the mirabegron group between the 2nd week and the 4th week (p

Climate change and urbanization have led to an increase in extreme weather and urban heat islands. Green space can help regulate the thermal environment, but previous studies have focused on two-dimensional (2D) indicators, neglecting the intrinsic three-dimensional (3D) characteristics of green space. Therefore, we developed a set of 3D landscape indices to define green space configurations, including characteristic, shape, and compactness, based on landscape ecology and the law of universal gravity, and quantify its benefits for the thermal environment. We collected high-resolution LiDAR point cloud data from Siming Mountain, China, to calculate both 2D and 3D green space landscape patterns and investigate their effects on land surface temperature (LST) using correlation analysis and spatial statistical methods. Our study revealed: (1) All the selected green space landscape indices had a significant negative effect on LST, with a non-linear enhancement when 2D or 3D indices interacted. (2) The 3D compactness index (VCI) could be the most reliable and concise index to explain LST spatial distribution. Adjusting the VCI allowed us to reduce the LST of the study area by up to 3.71 °C in summer and 2.14 °C in winter. However, an overly compact 3D green space above the threshold could lead to higher LST in summer. (3) Terrain had a weaker effect on LST in winter than in summer, and it showed a stronger interaction with the 3D form of green space than with the 2D form. We concluded that the 3D compact form of green space can be utilized as the key factor in maximizing its cooling effect, by taking into account both terrain factors and seasonal variations. Our study can shed light on the scientific planning of green space aiming at optimizing the thermal environment for more sustainable forest and urban habitats.

Rapid urbanization leads to a discrepancy between building operational energy consumption carbon emissions (BECCE) and urban sustainable development. Urban greenspace, which modifies local microclimates and thus BECCE, plays a critical part in reducing BECCE. To improve our scientific understanding and further explore the ecological effect of urban greenspace landscape pattern on BECCE, this study proposed an innovative method for modeling the accessibility to greenspace ecological effect to reduce BECCE. Accessibility was calculated using source–sink landscape theory as the theoretical basis and an improved potential model as the numerical basis. The normalized compactness index was adopted to measure the overall resistance to the ecological process and consider compact urban morphology. A case study of 67 office buildings in China demonstrated the applicability and implications of the model. The study found that i) total area and landscape shape index of greenspace, which represent source accessibility, are both significantly negatively correlated with BECCE; ii) landscape shape index of greenspace, which represents source accessibility and reflects greenspace landscape complexity, figures prominently in building carbon reductions and improves model predictions. The newly developed model can be used to identify optimal arrangements of urban green infrastructure to reduce BECCE under current conditions of intense urban land use, make projections of carbon emissions, and support decision makers in implementing nature-based solutions to achieve carbon emission peak and carbon neutrality goals.

Abstract Objective Stroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction. Methods The clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented. Results All 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038). Conclusion Trousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.

BackgroundPublic places are frequently polluted by cigarette smoking, and there is a lack of accurate, real-time, and intelligent monitoring technology to identify smoking behavior. It is necessary to develop a tool to identify cigarette smoking behavior in public places for more efficient control of cigarette smoking and better indoor air quality. ObjectiveTo construct a model for recognizing cigarette smoking behavior based on real-time indoor concentrations of PM2.5 in public places. MethodsReal-time indoor PM2.5 concentrations were measured for at least 7 continuous days in 10 arbitrarily selected places (6 public service providers and and 4 office or other places) from Oct. to Nov. 2022 in Pudong New Area, Shanghai. Indoor nicotine concentrations were monitored with passive samplers simultaneously. Outdoor PM2.5 concentration data were obtained from three municipal environmental monitoring stations which were nearest to each monitoring point during the same period. Mann-Whitney U test was used to compare indoor and outdoor means of PM2.5 concentrations, and Spearman rank correlation was used to analyze indoor PM2.5 and nicotine concentrations. An interactive plot and a random forest model was applied to examine the association between video observation validated indoor smoking behavior and real-time indoor PM2.5 concentrations in an Internet cafe. ResultsThe average indoor PM2.5 concentration in the places providing public services [(97.5±149.3) µg·m−3] was significantly higher than that in office and other places [(19.8±12.2) µg·m−3] (P=0.011). The indoor/outdoor ratio (I/O ratio) of PM2.5 concentration in the public service providers ranged from 1.1 to 19.0. Furthermore, the indoor PM2.5 concentrations in the 10 public places were significantly correlated with the nicotine concentrations (rs=0.969, P

Providing accurate crop yield estimations at large spatial scales and understanding yield losses under extreme climate stress is an urgent challenge for sustaining global food security. While the data-driven deep learning approach has shown great capacity in predicting yield patterns, its capacity to detect and attribute the impacts of climatic extremes on yields remains unknown. In this study, we developed a deep neural network based multi-task learning framework to estimate variations of maize yield at the county level over the US Corn Belt from 2006 to 2018, with a special focus on the extreme yield loss in 2012. We found that our deep learning model hindcasted the yield variations with good accuracy for 2006-2018 (R2 = 0.81) and well reproduced the extreme yield anomalies in 2012 (R2 = 0.79). Further attribution analysis indicated that extreme heat stress was the major cause for yield loss, contributing to 72.5% of the yield loss, followed by anomalies of vapor pressure deficit (17.6%) and precipitation (10.8%). Our deep learning model was also able to estimate the accumulated impact of climatic factors on maize yield and identify that the silking phase was the most critical stage shaping the yield response to extreme climate stress in 2012. Our results provide a new framework of spatio-temporal deep learning to assess and attribute the crop yield response to climate variations in the data rich era.

Chengdao Oilfield is located in the modern Yellow River underwater delta, where the seabed strata are complex, and the sediment silt and silty clay have great interbedding changes. In recent years, an increasing number of jack-ups are installed and removed in the same wellhead or similar wellhead. There are risks of sliding pile, punch-through, and liquefaction and subsidence in the area where piles are repeatedly inserted and pulled out on offshore moving platform. Aimed at the risks, preventive measures are analyzed to reduce the risk of pile driving on jack-up platforms.

In the course of towing of offshore platform, it is of great significance to calculate the towing resistance ahead of time and select the main tugboat with proper power for towing safety. In this paper, the calculation formulas or recommended methods for towing resistance of mainstream classification societies were investigated, and a CFD/AQWA finite element numerical simulation was conducted for the typical jack-up offshore platform in Shengli Petroleum Engineering Company.Based on the comparative analysis of the results, a suitable model for the calculation of towing resistance of platforms in domestic waters was optimized, and a suitable towing factor of safety was proposed.

This paper presents a simplified elastic continuum method for calculating the restraint effect of isolation piles on tunneling-induced vertical ground displacement, which can consider not only the relative sliding of the pile‒soil interface but also the pile row–soil interaction. The proposed method is verified by comparisons with existing theoretical methods, including the boundary element method and the elastic foundation method. The results reveal the restraining mechanism of the isolation piles on vertical ground displacements due to tunneling, i.e. the positive and negative restraint effects exerted by the isolation piles jointly drive the ground vertical displacement along the depth direction from the original tunneling-induced nonlinear variation situation to a relatively uniform situation. The results also indicate that the stiffness of the pile‒soil interface, including the pile shaft‒surrounding soil interface and pile tip-supporting soil interface, describes the strength of the pile‒soil interaction. The pile rows can confine the vertical ground displacement caused by the tunnel excavation to the inner side of the isolation piles and effectively prevent the vertical ground displacement from expanding further toward the outer side of the isolation piles.

Anaplasma capra is an emerging tickborne human pathogen initially recognized in China in 2015; it has been reported in ticks and in a wide range of domestic and wild animals worldwide. We describe whole-genome sequences of 2 A. capra strains from metagenomic sequencing of purified erythrocytes from infected goats in China. The genome of A. capra was the smallest among members of the genus Anaplasma. The genomes of the 2 A. capra strains contained comparable G+C content and numbers of pseudogenes with intraerythrocytic Anaplasma species. The 2 A. capra strains had 54 unique genes. The prevalence of A. capra was high among goats in the 2 endemic areas. Phylogenetic analyses revealed that the A. capra strains detected in this study were basically classified into 2 subclusters with those previously detected in Asia. Our findings clarify details of the genomic characteristics of A. capra and shed light on its genetic diversity.

When asynchronous motors, especially double-fed asynchronous motors in large capacity pump storage are the main loads in the high voltage direct current (HVDC) receiving end power grid, the increase of the equivalent slip of asynchronous motor load may cause transient voltage instability. In order to recover the voltage rapidly in the grid, the emergency reactive power support needs to be quick and accurate. A method for transient voltage stability emergency control by temporarily reducing DC current is proposed, the inverter station is used as emergency reactive power source for the HVDC receiving end power grid. In detail, firstly, aiming at the quantitative calculation of DC current, a nonlinear optimization model with the optimization variable of DC current and the objective of minimizing energy transmission reduction of HVDC is established. Further, in order to achieve fast solution and meet the accuracy requirements, global orthogonal collocation (GOC) is incorporated into the optimization model to transform the differential equations of both objective function and constraints into algebraic equations, thus the optimization is transformed into a nonlinear programming (NLP) problem, by which the emergency control strategy, in specific, the optimal DC current control scheme is obtained. Finally, the modified IEEE 14 benchmark is used to verify the effectiveness and superiority of the proposed strategy.

Gas-fired units provide great flexibility to accommodate the intermittent nature of renewable energy sources and are also considered to be an ideal substitute for retiring coal-fired generations. However, the increasing deployment of gas-fired units deepens interdependency between electric power and natural gas, calling for efficient modeling of the heterogeneous energy flow in the integrated electricity–gas systems (IEGS). Plenty of research works show the necessity of considering gas flow transients in the IEGS, which can be described by a set of partial differential equations (PDEs). To ensure a tractable optimization, the PDEs are often discretized using the finite/infinite difference method, which may result in a large computational scale for achieving good precision. To this end, this paper proposes an efficient model for capturing gas flow transients in the IEGS, which can be taken as the operational constraints in the optimal energy flow model for IEGS coordinated planning, scheduling, and control. For improving the computational efficiency, the PDE-based transient gas flow model is discretized using a space–time orthogonal collocation (OC) method, which provides high-quality results using fewer spatial–temporal discrete points than differential methods. Further, aiming at the difficulty in the determination of the number of space–time collocation points, an adaptive strategy is proposed and embedded in the proposed model utilizing the local fitting errors of state variables related to pipelines. Case studies show the superiority in computational accuracy and efficiency of the proposed model over the existing models based on Wendorff difference and global OC. And an illustrative case based on the modified IEGS benchmark system composed of the IEEE 118-bus power system and the Belgian 20-node gas network exhibits the application value of the proposed model in the optimization and control of the IEGS.

Sn-doped Ga2O3 thin films and metal–semiconductor–metal (MSM) ultraviolet detectors were prepared using the co-sputtering method to enhance their photoelectric performance. The results revealed that Sn doping can effectively change the optical and electrical properties of thin films, greatly improving the photoelectric responsiveness of the devices. Through microstructure testing results, all of the thin film structures were determined to be monoclinic beta phase gallium oxide. At a DC power of 30 W, the thickness of the Sn-doped thin film was 430 nm, the surface roughness of the thin film was 4.94 nm, and the carrier concentration, resistivity, and mobility reached 9.72 × 1018 cm−3, 1.60 × 10−4 Ω·cm, and 45.05 cm3/Vs, respectively. The optical results show that Sn doping clearly decreases the transmission of thin films and that the bandgap can decrease to 3.91 eV. Under 30 W DC power, the photo dark current ratio of the detector can reach 101, time responses of tr = 31 s and tf = 22.83 s were obtained, and the spectral responsivity reached 19.25 A/W.