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Abstract Background This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). Methods In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. Results The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values

Abstract The complex anatomy and biology of craniofacial bones pose difficulties in their effective and precise reconstruction. Injectable hydrogels (IHs) with water-swollen networks are emerging as a shape-adaptive alternative for noninvasively rebuilding craniofacial bones. The advent of versatile nanomaterials (NMs) customizes IHs with strengthened mechanical properties and therapeutically favorable performance, presenting excellent contenders over traditional substitutes. Structurally, NM-reinforced IHs are energy dissipative and covalently crosslinked, providing the mechanics necessary to support craniofacial structures and physiological functions. Biofunctionally, incorporating unique NMs into IH expands a plethora of biological activities, including immunomodulatory, osteogenic, angiogenic, and antibacterial effects, further favoring controllable dynamic tissue regeneration. Mechanistically, NM-engineered IHs optimize the physical traits to direct cell responses, regulate intracellular signaling pathways, and control the release of biomolecules, collectively bestowing structure-induced features and multifunctionality. By encompassing state-of-the-art advances in NM-integrated IHs, this review offers a foundation for future clinical translation of craniofacial bone reconstruction.

Abstract Background Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Purpose To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. Methods BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1β. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. Results BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/β-catenin signaling, regardless of IL-1β presence or duration of exposure. This inhibition of the Wnt/β-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. Conclusions PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/β-catenin signaling, irrespective of inflammatory conditions.

Abstract Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold–gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and −0.19% FS in the range of 0–20 MPa and −40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

Abstract Aims Few studies have investigated differences in sequential transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and simultaneous RFA‐TACE for the treatment of hepatocellular carcinoma (HCC) using the Milan criteria. This study explored the differences in safety and prognosis between sequential TACE‐RFA and simultaneous RFA‐TACE. Methods This retrospective real‐world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE‐RFA (n = 75) or simultaneous RFA‐TACE (n = 34) at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021. Postoperative complications, length of hospital stay, and long‐term prognosis were compared. The median follow‐up duration of these patients was 39.1 months. Overall survival (OS) and time to tumor recurrence (TTR) curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test. Independent risk factors for OS and tumor recurrence (TR) were analyzed using the Cox risk regression model. Results Multivariate analysis showed that tumor diameter >3 cm (hazard ratio [HR]: 2.201, 95% confidence interval [CI]: 1.106–4.378, p = 0.025; HR: 2.236, 95% CI: 1.271–3.934, p = 0.005, respectively) and alpha‐fetoprotein (AFP) > 400 μg/L (HR: 2.362, 95% CI: 1.195–4.668, p = 0.013; HR: 1.798, 95% CI: 1.048–3.086, p = 0.033, respectively) were independent risk factors for OS and TTR, whereas the presence of multiple tumors (HR: 2.352, 95% CI: 1.127–4.907, p = 0.023) was an independent risk factor for TTR. Simultaneous RFA‐TACE did not have an effect on OS or TTR. After propensity score‐matched, comparable results were obtained and RFA‐TACE still had no effect on OS or TTR. No significant differences were observed in grade III/IV complications (2/75 [2.7%] vs. 1/34 [2.9%], p = 1.000) between the two groups. However, the RFA‐TACE group had fewer complications than the TACE‐RFA group (24/34 [70.6%] vs. 66/75 [88.0%], p = 0.026). The RFA‐TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE‐RFA group (6.0 vs. 10.0 days, p

Abstract Melanoma's high metastatic potential, especially to the brain, poses significant challenges to patient survival. The blood‒brain barrier (BBB) is a major obstacle to the effective treatment of melanoma brain metastases. We screened antipsychotic drugs capable of crossing the BBB and identified penfluridol (PF) as the most active candidate. PF reduced melanoma cell viability and induced apoptosis. In animal models, PF effectively inhibited melanoma growth and metastasis to the lung and brain. Using immunoprecipitation combined with high‐resolution mass spectrometry, and other techniques such as drug affinity responsive target stability, we identified CIP2A as a direct binding protein of PF. CIP2A is highly expressed in melanoma and its metastases, and is linked to poor prognosis. PF can restore Protein Phosphatase 2A activity by promoting CIP2A degradation, thereby inhibiting several key oncogenic pathways, including AKT and c‐Myc. Additionally, von Hippel‒Lindau (VHL) is the endogenous E3 ligase for CIP2A, and PF enhances the interaction between VHL and CIP2A, promoting the ubiquitin‒proteasome degradation of CIP2A, thereby inhibiting melanoma growth and metastasis. Overall, this study not only suggests PF's potential in treating melanoma and its brain metastases but also highlights CIP2A degradation as a therapeutic strategy for melanoma.

Abstract To investigate the percolation mechanism of tight sandstone reservoirs, qualitative and quantitative methods are applied to analyze the pore structure of the Ordos Basin through scanning electron microscopy and high-pressure mercury injection. Based on gas–water relative permeability data and the visualization of real sandstone models, a gas–water displacement experiment was carried out to simulate the percolation mechanism and fluid distribution of different pore types. The results show that: ① The percolation of different pore types varies greatly, and the irreducible water saturation decreases when the reservoir properties improve. The relative permeability of gas at an irreducible water saturation increases, the width of the two-phase percolation area increases, and the percolation ability is enhanced as the reservoir properties improve. ② The gas–water displacement mode changes from fingering to uniform displacement with the improvement of pore type, which is beneficial to the formation of effective reservoirs filled with natural gas under the same hydrocarbon generation conditions. ③ The time required for the pressure relief of samples with good reservoir properties is short, and the recovery is higher with the improvement of pore type. ④ The residual water in samples with a poor pore type increases, which decreases the relative permeability of gas and recovery. A reasonable development pattern should be carried out, and the production pressure difference should be strictly controlled to maximize productivity. This study provides theoretical guidance for the development of tight sandstone reservoirs in the Ordos Basin.

Abstract Comprehensive evaluation of reservoirs is an important link in gas reservoir exploration and development. The evaluation of tight carbonate reservoirs often focuses on the characteristics of porosity and permeability, ignoring the important factor of fractures, also the quantitative evaluation of reservoirs is relatively few. It is difficult to identify fractures and evaluate the reservoir factors qualitatively and quantitatively. Herein, the sedimentary microfacies and microporosity of the tight carbonate reservoir of the Ma55 submember in the eastern Sulige area are comprehensively studied by casting thin section, rock physical property, and capillary pressure test data. The backpropagation (BP) neural network algorithm is used to identify and predict fractures. Finally, through the analytic hierarchy process, the above reservoir influencing factors are modeled and quantitatively analyzed for reservoir evaluation. The results show that the highest probability of fracture development in the central and northwest areas of the study area can reach 0.92. The accuracy of the BP neural network model in identifying cracks can reach 80%, which is reliable and effective compared with the conventional logging identification method. Reservoirs can be classified into four types according to their quality. The synthetic weights of porosity, permeability and fracture development probability are 0.2, 0.2 and 0.216 respectively, which are the three most important evaluation parameters. This study improves the accuracy of fracture identification and prediction of tight reservoirs in comprehensive reservoir evaluation, which provides guidance and scheme for more detailed exploration and development of tight carbonate reservoirs.

Abstract Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract and a leading cause of cancer-related death worldwide. Since many CRC patients are diagnosed already in the advanced stage, and traditional chemoradiotherapy is prone to drug resistance, it is important to find new therapeutic targets. In this study, the expression levels of ALDOA and p-AKT were detected in cancer tissues and paired normal tissues, and it was found that they were significantly increased in CRC tissues, and their high expression indicated poor prognosis. Moreover, a positive correlation between the expression of ALDOA and p-AKT was found in CRC tissues and paired normal tissues. In addition, the Kaplan–Meier analysis revealed that the group with both negative of ALDOA/p-AKT expression had longer five-year survival rates compared with the other group. Besides, the group with both high expression of ALDOA/p-AKT had a worse prognosis compared with the other group. Based on the expression of ALDOA and p-AKT in tumor tissues, we can effectively distinguish tumor tissues from normal tissues through cluster analysis. Furthermore, we constructed nomograms to predict 3-year and 5-year overall survival, showing that the expression of ALDOA/p-AKT plays a crucial role in predicting the prognosis of CRC patients. Therefore, ALDOA/p-AKT may act as a crucial role in CRC, which may provide new horizons for targeted therapies for CRC.

Introduction: Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood.Materials and methods: Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response.Results: The genomic landscape exhibited that the most commonly altered genes in HCC were TP53, FAT3, PDE4DIP, KMT2C, FAT1, and MYO18A, while TP53, FAT1, FAT3, PDE4DIP, ROS1, and GALNT11 were frequently altered in ICC; notably, KRAS (18.18% vs. 1.29%) and BAP1 (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that LDLR, MSH2, KDM5D, PDE3A, and FOXO1 were frequently altered in the VI group compared to patients without VIs. Compared to the right hepatic lobes of HCC patients, the left hepatic lobe of HCC patients had superior OS (median OS: 36.77 months vs. unreached, p < 0.05). By further comparison, Notch signaling pathway-related alterations were significantly prevalent among the right hepatic lobes of HCC patients. Of note, multivariate Cox regression analysis showed that altered RB1, NOTCH3, MGA, SYNE1, and ZFHX3, as independent prognostic factors, were significantly correlated with the OS of HCC patients. Furthermore, altered LATS1 was abundantly enriched in the HCC-recurrent group, and impressively, it was independent of clinicopathological features in predicting RFS (median RFS of altered type vs. wild-type: 5.57 months vs. 22.47 months, p < 0.01). Regarding those treated HCC patients, TMB value, altered PTPRZ1, and cell cycle-related alterations were identified to be positively associated with the objective response rate (ORR), but KMT2D alterations were negatively correlated with ORR. In addition, altered KMT2D and cell cycle signaling were significantly associated with reduced and increased time to progression-free survival (PFS), respectively.Conclusion: Comprehensive genomic profiling deciphered distinct molecular characterizations underlying VI, location of onset, recurrence, and survival time in liver cancer. The identification of novel genetic predictors of response to anti-PD-1 plus bevacizumab in HCC facilitated the development of an evidence-based approach to therapy.

Objectives: To explore the effects of perioperative SARS-CoV-2 Omicron infection on postoperative complications in patients with liver cancer. Methods: A propensity-matched study was conducted, which included patients with primary liver cancer who underwent hepatectomy from September 01, 2022 to January 20, 2023. Patients who infected SARS-CoV-2 Omicron during the perioperative period (7 days before to 30 days after surgery) were matched 1:1 with noninfected patients. The primary outcomes, which were COVID-19-related major complications and liver resection-specific complications, were analyzed using multivariate logistic regression. Results: A total of 243 patients were included, with 63 cases of perioperative infections, of which 62 were postoperative infections. The overall 30-day postoperative mortality rate was 1.6% (4/243). Compared to noninfected patients, those with perioperative infections showed no significant difference in the occurrence of adverse postoperative outcomes. However, they had a higher rate of 30-day readmission after surgery (11.1% vs 0%, P = 0.013). Perioperative SARS-CoV-2 infection was not associated with “major cardiorespiratory complications” or “liver resection-specific complications”, but age, pre-existing comorbidities, and tumor type were related to these outcomes. Conclusion: Perioperative SARS-CoV-2 Omicron infection did not increase the incidence of postoperative complications in patients with liver cancer. However, those patients had a higher rate of 30-day readmission after surgery.

Abstract The cryptocurrency market is a complex and rapidly evolving financial landscape in which understanding the inter- and intra-asset dependencies among key financial variables, such as return and liquidity, is crucial. In this study, we analyze daily return and liquidity data for six major cryptocurrencies, namely Bitcoin, Ethereum, Ripple, Binance Coin, Litecoin, and Dogecoin, spanning the period from June 3, 2020, to November 30, 2022. Liquidity is estimated using three low-frequency proxies: the Amihud ratio and the Abdi and Ranaldo (AR) and Corwin and Schultz (CS) estimators. To account for autoregressive and persistent effects, we apply the autoregressive integrated moving average-generalized autoregressive conditional heteroscedasticity (ARIMA-GARCH) model and subsequently utilize the copula method to examine the interdependent relationships between the return on and liquidity of the six cryptocurrencies. Our analysis reveals strong cross-asset lower-tail dependence in return and significant cross-asset upper-tail dependence in illiquidity measures, with more pronounced dependence observed in specific cryptocurrency pairs, primarily involving Bitcoin, Ethereum, and Litecoin. We also observe that returns tend to be higher when liquidity is lower in the cryptocurrency market. Our findings have significant implications for portfolio diversification, asset allocation, risk management, and trading strategy development for investors and traders, as well as regulatory policy-making for regulators. This study contributes to a deeper understanding of the cryptocurrency marketplace and can help inform investment decision making and regulatory policies in this emerging financial domain.

Abstract Pressure sensors play a vital role in aerospace, automotive, medical, and consumer electronics. Although microelectromechanical system (MEMS)-based pressure sensors have been widely used for decades, new trends in pressure sensors, including higher sensitivity, higher accuracy, better multifunctionality, smaller chip size, and smaller package size, have recently emerged. The demand for performance upgradation has led to breakthroughs in sensor materials, design, fabrication, and packaging methods, which have emerged frequently in recent decades. This paper reviews common new trends in MEMS pressure sensors, including minute differential pressure sensors (MDPSs), resonant pressure sensors (RPSs), integrated pressure sensors, miniaturized pressure chips, and leadless pressure sensors. To realize an extremely sensitive MDPS with broad application potential, including in medical ventilators and fire residual pressure monitors, the “beam-membrane-island” sensor design exhibits the best performance of 66 μV/V/kPa with a natural frequency of 11.3 kHz. In high-accuracy applications, silicon and quartz RPS are analyzed, and both materials show ±0.01%FS accuracy with respect to varying temperature coefficient of frequency (TCF) control methods. To improve MEMS sensor integration, different integrated “pressure + x” sensor designs and fabrication methods are compared. In this realm, the intercoupling effect still requires further investigation. Typical fabrication methods for microsized pressure sensor chips are also reviewed. To date, the chip thickness size can be controlled to be

Abstract The carbonate rock formations have obvious dual media characteristics, fracture development and good physical conditions, which are the main seepage channels and storage spaces for gas after the reconstruction of underground gas storage. The carbonate strata of the Ordovician system are important natural gas reservoirs in the eastern area of Sulige Gas Field in the Ordos Basin, and the identification and characterization of their fractures are of great significance for the modeling of fractures in the later stage and the improvement of the operation scheme of the gas storage. At present, there is little research on fractures, which restricts exploration and development. Therefore, taking the 39–61 gas storage reservoir in the eastern area of Sulige Gas Field in the Ordos Basin as the research object, this paper identifies and studies the characteristics of the fractures by core, microscopic, conventional logging curves, and imaging logging identification. The results show that the fracture length ranges from 5 to 15 cm and the width ranges from 0.1 to 3 mm. The fracture angles are mostly between 75° and 90° and the main direction is NW–SE. In conventional logging curves, porosity logging has a good response to fractures, while resistivity logging has a general response to fractures; In layers with more developed fractures, natural gamma values are mostly higher than 40API, rock volume density is less than 2.8 g/cm3, neutron porosity is greater than 12.5%, and acoustic time difference is greater than 160 μ s/m. This study is of great significance for improving the identification of carbonate fractures, enriching the relevant theories, and providing guidance for the construction of carbonate gas storage.

The concrete lining of high-pressure water conveyance tunnels permeates under high-pressure water. Dense and hydrophobic coating can effectively improve the impermeability of concrete. However, the coating exhibits varying impermeability in different high-pressure environments, which can even lead to coating detachment or damage. The objectives of this study are to improve the high-pressure impermeability of concrete by using a polymer coating, and to study the varying impermeability through experiments. This study applied a polymer coating called SCU-SD-SP-II (SSS) to concrete surfaces, and it formed a composite protective layer with an epoxy-modified silicone (EMS) coating. A series of high-pressure impermeability tests were conducted to study the seepage regulation of the coated concrete and the failure mechanism of the SSS coating under cracks in the concrete. The results indicate that the SSS coating has excellent impermeability. Pressurized water of 3 MPa could not permeate the SSS coating with a thickness of 0.5 mm within 24 h. Under both external and internal water pressure conditions, the SSS coatings improved concrete impermeability. Additionally, the average seepage height and relative permeability coefficient of the latter decreased by 49.6% and 71.2%, respectively, compared with the former. After concrete cracking, the SSS coating could withstand 3 MPa pressure on crack surfaces smaller than 1 mm. When the crack width was greater than 2 mm, the SSS coating deformed under 1 MPa pressure. As the pressure increased to 2 MPa or even 3 MPa, the SSS coating was punctured or torn due to stress concentration. This study provides new insights into the impermeability of concrete under high water pressure.

The high temperature of modern electronic devices poses great challenges to the safety and reliability of applications. Reasonable and effective control of device operating temperature for enhancing device performance and promoting the development of the electronics industry has a positive effect. Here, an innovative and efficient passive cooling technology is proposed to reduce the device temperature using polymerized metal fin and smart hydrogel to form smart fin. The smart fin carries away the waste heat generated by the device through evaporation and regeneration is accomplished by capturing water molecules from the environment. The smart fin is demonstrated to low down the temperature of a heater with heat flux of 2900 W/m2 by 48.3 °C and restores to its initial state after 160 min. At a threshold temperature of 60 °C, it promoted the maximum usage power by 49.4%. The evaporation and regeneration capacity of the smart fin can be controlled by ambient temperature, relative humidity, and smart hydrogel thickness. Specifically, high temperatures promote water evaporation and absorption, high humidity suppresses evaporation but favors absorption, and excessive thickness impedes water transport. This thermal management strategy with simple structure, low-cost, and easy-preparation is expected to become a universal technology in the electronics industry.

Background: Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA1c analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management. Case report: In this study, we present the case of a 23-year-old man with undetectable HbA1c levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA1c absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of β-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del). Conclusion: The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA1c analysis.

In this study, the morphology characteristics and formation mechanism of channel segregation in the industrial-sized Ti–Nb binary ingots produced by vacuum arc remelting (VAR) are researched based on experiments and calculations. The results show that the channel segregation is usually located at the 1/4–3/4 radius of the ingot and the morphology is closely related to the VAR process. The Ti-enriched channel segregation stripes tend to parallel to the ingot centerline and columnar dendrites in steady-state remelting region and hot-top region, respectively, while along the molten pool profile in residual molten pool region. For the first time, the Ti2O3 particles precipitated in the channel segregation were observed, following the orientation relationship of β//Ti2O3 and {11‾0}β//{011‾}Ti2O3 with β matrix in coherent boundary. First-principles calculations evident that the enrichment of Ti-solute tends to decrease the formation enthalpy, and hence makes for the precipitation of Ti2O3 particles. The numerical simulation and the experiment results manifest that the channel segregation originates from the convergence of interdendritic Ti-enriched liquid, resulting in the density inversion between the Ti-enriched initiation site and the surrounding liquid. The density gradient and the solidification rate dominate the growth direction and the radius distribution of the channel segregation. Based on the above, an optimized technique with helium cooling and the external stirring magnetic field was conducted and the channel segregation was eliminated successfully.

Abstract Flexible electronics have demonstrated various strategies to enhance the sensory ability for tactile perception and wearable physiological monitoring. Fibrous microstructures have attracted much interest because of their excellent mechanical properties and fabricability. Herein, a structurally robust fibrous mat was first fabricated by electrospinning, followed by a sequential process of functionalization utilizing ultrasonication treatment and in situ polymerization growth. Electrospun polyurethane (PU) microfibers were anchored with multi-walled carbon nanotubes (MWCNTs) to form conductive paths along each fiber by a scalable ultrasonic cavitation treatment in an MWCNT suspension. After, a layer of poly(3,4-ethylene dioxythiophene) (PEDOT) was grown on the surface of PU fibers decorated with MWCNTs to enhance the conductive conjunctions of MWCNTs. Due to the superior electromechanical behaviors and mechanical reinforcement of PEDOT, the PEDOT/MWCNT@PU mat-based device exhibits a wide working range (0–70 kPa), high sensitivity (1.6 kPa−1), and good mechanical robustness (over 18,000 cycles). The PEDOT/MWCNT@PU mat-based sensor also demonstrates a good linear response to different temperature variations because of the thermoelectricity of the PEDOT/MWCNT composite. This novel strategy for the fabrication of multifunctional fibrous mats provides a promising opportunity for future applications for high-performance wearable devices.

Mineralization characterized by Au, Hg, and Tl enrichment is rare, and research on Au, Hg, and Tl mineralization is limited. The Lanmuchang Au–Hg–Tl deposit is located in the “Golden Triangle” of Yunnan, Guizhou, and Guangxi Provinces in China. In this study, we used scanning electron microscopy (SEM), electron microprobe analysis (EPMA), and a Tescan integrated mineral analyzer (TIMA) to analyze the mineral composition and distribution of the different types of ores and identify the occurrence state and enrichment mechanism of ore-forming elements in the Lanmuchang deposit. The results show that the primary ore minerals in the Lanmuchang deposit are pyrite, cinnabar, and lorandite. Cinnabar is the primary carrier of Hg (>90%), and pyrite is the primary carrier of Tl (>60%). Gold, Hg, and Tl primarily occur as solid solutions in hydrothermal pyrite, whereas they primarily occur as nano-scale particles in diagenetic pyrite. The substitution of As for S in hydrothermal pyrite promotes Au enrichment. The coupled substitution of 2Fe2+ ⇔ Tl+ + As3+ may be a significant Tl incorporation mechanism and promotes the occurrence of Hg in pyrite. The As and Se contents and Cu/Au and Co/Ni ratios of the hydrothermal pyrite demonstrate that the ore-forming fluid was mostly in a low-temperature, low-salinity, almost-neutral pH, and nearly reducing environment. The results show that the mineralization of the Lanmuchang deposit is associated with the cooling, oxidation, water–rock interaction, and boiling processes of the ore-forming fluid(s).

Traditional ventilation methods consume excessive energy but still fail to meet requirements in underground tunnel group construction. Thus, a closed-loop intelligent control system for ventilation-on-demand (VOD) was developed. To address dynamic changes in ventilation load and reduce energy consumption, firstly, the developed system calculates the real-time ventilation load and establishes a ventilation-network-based control mode to represent the ventilation system structure. The deep deterministic policy gradient (DDPG) method was then employed for the closed-loop control ensuring the required air volume in each branch of tunnel groups while minimizing energy consumption. After that, the developed closed-loop intelligent ventilation control system encompasses comprehensive perception, real analysis, real-time control, and continuous optimization. This system treats decision-making, control, and feedback as subsystems that reflect the adaptability between ventilation efficiency, construction progress, and power consumption. Finally, the end-edge-cloud-based software of the system was developed to enable remote control and display on large screens, personal computers (PCs), and mobile applications (Apps) to ensure precise and timely operation. The system was employed in tunnel group under construction at the Xulong Hydropower Station in Southwestern China, and the obtained results validate its advanced closed-loop control based on reinforcement learning (RL) and confirm its feasibility in engineering practice.

Abstract Background Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied. Methods To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed. Results JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in “cancer-related pathways” and “EGFR-related signaling pathways”, which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively). Conclusions The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy. Graphical Abstract

The underground hydropower projects in Southwest China is characterized by large excavation sizes, high geostresses, complicated geological conditions and multiple construction processes. Various disasters such as collapses, large deformations, rockbursts are frequently encountered, resulting in serious casualties and huge economic losses. This review mainly presents some representative results on microseismic (MS) monitoring and forecasting for disasters in hydropower underground engineering. First, a set of new denoising, spectral analysis, and location methods were developed for better identification and location of MS signals. Then, the tempo-spatial characteristics of MS events were analyzed to understand the relationship between field construction and damages of surrounding rocks. Combined with field construction, geological data, numerical simulation and parametric analysis of MS sources, the focal mechanism of MS events was revealed. A damage constitutive model considering MS fracturing size was put forward and feedback analysis considering the MS damage of underground surrounding rocks was conducted. Next, an MS multi-parameter based risk assessment and early warning method for dynamic disasters were proposed. The technology for control of the damage and deformation of underground surrounding rocks was proposed for underground caverns. Finally, two typical underground powerhouses were selected as case studies. These achievements can provide significant references for prevention and control of dynamic disasters for underground engineering with similar complicated geological conditions.

Abstract Background The precise mechanisms of hormone action responsible for the full course of events modulating folliculogenesis in crocodilian have not been determined, although histological features have been identified. Results The Alligator sinensis ovarian morphological characteristics observed at 1, 15, 30, 60, 90, and 300 days post hatching(dph) revealed that the dynamic changes in germ cells varied in different meiotic and developmental stages, confirming that the processes of folliculogenesis were protracted and asynchronous. The presence of endogenous follicle-stimulating hormone(FSH) mRNA and protein expression within the cerebrum at 1 dph, in parallel with the increase in germ cells within the germ cell nests(Nest) from 1 dph to 15 dph, suggested that endocrine regulation of the pituitary-gonad axis is an early event in oogonia division. Furthermore, the endogenous expression of FSH showed a trend of negative feedback augmentation accompanied by the exhaustion of maternal yolk E2 observed at 15 dph. Such significant elevation of endogenous FSH levels was observed to be related to pivotal events in the transition from mitosis to meiosis, as reflected by the proportion of oogonia during premeiosis interphase, with endogenous FSH levels reaching a peak at the earliest time step of 1 dph. In addition, the simultaneous upregulation of premeiotic marker STRA8 mRNA expression and the increase in endogenous FSH further verified the above speculation. The strongly FSHr-positive label in the oocytes within Pre-previtellogenic follicles was synchronized with the significant elevation of ovarian cAMP detected at 300 dph, which suggested that diplotene arrest maintenance during early vitellogenesis might be FSH dependent. In addition, preferential selection in asynchronous meiotic initiation has been supposed to act on somatic supportive cells and not directly on germ cells via regulation of FSH that in turn affects downstream estrogen levels. This suggestion was verified by the reciprocal stimulating effect of FSH and E2 on the accelerated meiotic marker SYCP3 and by the inhibited cell apoptosis demonstrated in ovarian cell culture in vitro. Conclusion The corresponding results contribute an expansion of the understanding of physiological processes and shed some light on the specific factors responsible for gonadotropin function in the early folliculogenesis of crocodilians.

Abstract Metal-organic frameworks (MOFs) are a sort of promising peroxidase-like nanozyme but face the challenge that the inorganic nodes in most of the MOF structures are generally blocked by the organic linkers. Further enhancement or activation of their peroxidase-like activity plays an important role in developing MOF-based nanozymes. Herein, a multimetallic nanoparticle (NP) decorated-MOF, Cu/Au/Pt NP decorated-Cu-TCPP(Fe) nanozyme (CuAuPt/Cu-TCPP(Fe)) was synthesized in situ and served as a peroxidase-like nanozyme. The peroxidase-like activity of this stable CuAuPt/Cu-TCPP(Fe) nanozyme was enhanced due to the decreased potential barriers for *OH generation in the catalytic process. Owing to the remarkable peroxidase-like activity, a CuAuPt/Cu-TCPP(Fe)-based colorimetric assay was established for the sensitive determination of H2O2 and glucose with the limit of detection (LOD) of 9.3 µM and 4.0 µM, respectively. In addition, a visual point-of-care testing (POCT) device was developed by integrating the CuAuPt/Cu-TCPP(Fe)-based test strips with a smartphone and was employed for a portable test of 20 clinical serum glucose samples. The results determined by this method agree well with the values deduced by clinical automatic biochemical analysis. This work not only represents an inspiration for the usage of MNP/MOF composite as a novel nanozyme for POCT diagnosis, but also provides a deeper insight and understanding into the enhanced enzyme-mimic effect of MNP-hybrid MOF composites, which in turn will guide the engineering of MOF-based functional nanomaterials. Graphical Abstract

Abstract Objective To investigate the risk factors for gastrointestinal perforation in metastatic colorectal cancer patients receiving bevacizumab. Methods We retrospectively reviewed 217 patients with metastatic colorectal cancer receiving bevacizumab to investigate the risk factors for gastrointestinal perforation. Three patients occurred intestinal perforation after receiving bevacizumab. We analyzed the clinical characteristics of three patients with intestinal perforation. Results All patients receiving bevacizumab. Three of 217 patients occurred intestinal perforation after receiving bevacizumab. Patient no. 1 was 70 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. Patient no. 2 was 59 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation after receiving bevacizumab, and recovered smoothly after symptomatic treatment. Patient no. 3 was 60 years old, female, having history of intestinal obstruction. The patient occurred intestinal perforation and ultimately died after receiving bevacizumab. Conclusions Patients with advanced colorectal cancer receiving bevacizumab are at risk of gastrointestinal perforation. The patient's age, gender and history of bowel obstruction may be associated with gastrointestinal perforation.

Objective. This study aims to evaluate the impact and predictive value of the preoperative NPRI on short-term complications and long-term prognosis in patients undergoing laparoscopic radical surgery for colorectal cCancer (CRC). Methods. A total of 302 eligible CRC patients were included, assessing five inflammation—and nutrition-related markers and various clinical features for their predictive impact on postoperative outcomes. Emphasis was on the novel indicator NPRI to elucidate its prognostic and predictive value for perioperative risks. Results. Multivariate logistic regression analysis identified a history of abdominal surgery, prolonged surgical duration, CEA levels ≥5 ng/mL, and NPRI ≥ 3.94 × 10−2 as independent risk factors for postoperative complications in CRC patients. The Clavien–-Dindo complication grading system highlighted the close association between preoperative NPRI and both common and severe complications. Multivariate analysis also identified a history of abdominal surgery, tumor diameter ≥5 cm, poorly differentiated or undifferentiated tumors, and NPRI ≥ 2.87 × 10−2 as independent risk factors for shortened overall survival (OS). Additionally, a history of abdominal surgery, tumor maximum diameter ≥5 cm, tumor differentiation as poor/undifferentiated, NPRI ≥ 2.87 × 10−2, and TNM Stage III were determined as independent risk factors for shortened disease-free survival (DFS). Survival curve results showed significantly higher 5-year OS and DFS in the low NPRI group compared to the high NPRI group. The incorporation of NPRI into nomograms for OS and DFS, validated through calibration and decision curve analyses, attested to the excellent accuracy and practicality of these models. Conclusion. Preoperative NPRI independently predicts short-term complications and long-term prognosis in patients undergoing laparoscopic colorectal cancer surgery, enhancing predictive accuracy when incorporated into nomograms for patient survival.

Abstract Patients with central nervous system (CNS) lymphoma face limited treatment options and poor treatment outcomes, emphasizing the urgent need for effective therapeutic strategies. One limiting factor contributing to the suboptimal efficacy is the inadequate penetration of most treatment drugs across the blood–brain barrier (BBB). Recent insights into the pathophysiology of CNS lymphoma have identified the Bruton's tyrosine kinase (BTK) signaling pathway as a potential target. Some clinical trials have shown impressive responses to BTK inhibitors in CNS lymphoma. However, currently approved BTK inhibitors have low BBB penetration rates, limiting their efficacy. In this study, we discovered that JDB175, a novel and highly selective BTK inhibitor, exhibits excellent BBB penetration capabilities and demonstrates favorable activity in a mouse model of CNS lymphoma while showing no significant signs of toxicity. JDB175 effectively inhibits the BTK signaling pathway in human lymphoma cells, suppressing their proliferation, inducing cell cycle arrest, and promoting apoptosis. The significance of this study lies in addressing the critical unmet medical need for effective treatments for CNS lymphoma. This finding indicates a promising avenue for improved treatments in CNS lymphoma, potentially opening doors for further clinical investigation and therapeutic advancements.

Triple negative breast cancer (TNBC) poses a significant clinical challenge due to its lack of targeted therapy options and the frequent development of chemotherapy resistance. Metastasis remains a primary cause of mortality in late-stage TNBC patients, underscoring the urgent need for alternative treatments. Repurposing existing drugs offers a promising strategy for the discovery of novel therapies. In this study, we investigated the potential of pimavanserin tartrate (PVT) as a treatment for TNBC. While previous studies have highlighted PVT's anticancer effects in various cancer types, its activity in TNBC remains unclear. Our investigation aimed to elucidate the anticancer effects and underlying mechanisms of PVT in TNBC. We evaluated the impact of PVT and combination treatments involving PVT on TNBC cell viability, apoptosis, autophagy, and associated signaling pathways. Our findings revealed that PVT may induce mitochondria-dependent intrinsic apoptosis and caused cytoprotective autophagy via the PI3K/Akt/mTOR pathway in TNBC cells in vitro. Notably, our study demonstrated strong synergistic anti-TNBC effects when combining PVT with doxorubicin. We also found PVT showed some efficacies to inhibit TNBC tumor growth in vivo. These results provided valuable insights into the potential of PVT as an anti-TNBC therapeutic and a possible option for enhancing the sensitivity of TNBC cells to conventional chemotherapy drugs. Further studies are needed to determine the activity and mechanism of PVT in inhibiting TNBC.

Abstract Anomaly detection aims at locating the spectral different objects of a specific scene without any prior information, and has gained increasing attention. By decomposing the input hyperspectral image (HSI) into a background tensor and an anomaly tensor, the tensor approximation is an efficient tool for detecting the anomalies. Low rankness is usually utilized as the regularizer during the background reconstruction process. Different from most existing hyperspectral anomaly detection methods which compute the truncated nuclear norm of the third folding of the original HSI, a novel weighted‐sparsity‐regularized tensor linear representation (WsrTLR) method is proposed for hyperspectral anomaly detection in this paper. Tensor linear representation is utilized to formulate the background HSI by a three‐dimensional (3D) representation base and the corresponding 3D representation coefficient. Low rankness is applied to constrict the representation coefficient, an operation which avoids destroying the multi‐way structure and losing information during the matrixing process, and ensures a satisfactory detection accuracy. Meanwhile, by incorporating the weighted‐sparsity‐regularized tensor linear representation to reconstruct the background tensor, the anomalies can be easily detected by eliminating the background tensor from the original scene. In addition, to avoid negative influence caused by the redundant bands and noisy bands in the representation process, informative bands have been first selected via an optimal neighborhood reconstruction strategy. Experimental results and data analysis on four real hyperspectral datasets, which contain anomalies with different sizes, have demonstrated the effectiveness of the proposed method.

In daily life, counterfeit and substandard products, particularly currency, medicine, food, and confidential documents, are capable of bringing about very serious consequences. The development of anti-counterfeiting and authentication technologies with multilevel securities is a powerful means to overcome this challenge. Among various anti-counterfeiting technologies, fluorescent anti-counterfeiting technology is well-known and commonly used to fight counterfeiters due to its wide material source, low cost, simple usage, good concealment, and simple response mechanism. Spiropyran is favored by scientists in the fields of anti-counterfeiting and information encryption due to its reversible photochromic property. Here, we summarize the current available spiropyran-based fluorescent materials from design to anti-counterfeiting applications. This review will be help scientists to design and develop fluorescent anti-counterfeiting materials with high security, high performance, quick response, and high anti-counterfeiting level.

The Youjiang Basin in China is the world’s second-largest concentrated area of Carlin-type Au deposits after Nevada, USA, boasting cumulative Au reserves nearing 1000 t. This study examined the recently unearthed Lintan Carlin-type Au deposit within the Youjiang Basin. Factor analysis and association rule algorithms were used to identify exploration vectors and indicators essential for navigating this promising geological territory. In the Lintan mining area, the geological strata encompass the Triassic Bianyang, Niluo, and Xuman formations comprised clastic rocks, followed by the deeper Permian Wujiaping Formation with massive carbonate rocks. The orebodies are restricted to the F14 inverse fault, cutting through the Xuman Formation, with an additional F7 fault between the Wujiaping and Xuman formations. A total of 125 rock samples from the F14 fault and a representative cross-section were analyzed for 15 elements (Au, Ag, As, Bi, Cd, Co, Cu, Hg, Mo, Ni, Pb, Sb, Tl, W, and Zn). The elements were divided into four groups based on cluster and factor analysis. Group 1 (Co, Cu, Zn, Ni, Tl, W, and Bi) was mainly enriched in the Xuman, Niluo, and Bianyang formations controlled by sedimentary diagenesis. Group 2 (Au, As, Hg, and Sb) was concentrated in the F14 and F7 faults, representing Au mineralization. Group 3 (Pb, Ag, and Mo) was mostly enriched near the F14 and F7 faults, displaying a peripheral halo of Au mineralization, and was probability controlled by ore-forming hydrothermal activities. Group 4 (Cd and Mo) exhibited extreme enrichment along the periphery of the F7 fault. This pattern indicates the presence of a substantial hydrothermal alteration zone surrounding the fault, likely influenced by ore-forming hydrothermal processes. Additionally, Pb, Ag, Cd, Mo, and W are considered essential indicators for ore formation besides Au, As, Sb, Hg, and Tl. Twelve effective association rules were derived using the association rule algorithm, which can aid in discriminating Au mineralization. The spatial distributions of the 15 elements indicated that the F14 fault is the main ore-bearing fracture zone, while the F7 fault serves as the ore-conducting structure, channeling ore-forming fluids into the F14 fault. Faults between the Wujiaping and Xuman formations, along with their associated reverse faults, present potential prospecting targets both within and outside the Lintan Au deposit in the Youjiang Basin. Exploration geochemical data can be fully utilized by combining factor analysis and association rule algorithms, offering key guidance for prospecting Carlin-type gold and similar deposits.

Background: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. Methods: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. Results: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. Conclusions: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.

To produce functional protective textiles with minimal environmental footprints, we developed durable superhydrophobic antimicrobial textiles. These textiles are characterized by a micro-pleated structure on polyester fiber surfaces, achieved through a novel plasma impregnation crosslinking process. This process involved the use of water as the dispersion medium, water-soluble nanosilver monomers for antimicrobial efficacy, fluorine-free polydimethylsiloxane (PDMS) for hydrophobicity, and polyester (PET) fabric as the base material. The altered surface properties of these fabrics were extensively analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS), thermogravimetric analysis (TGA), and water contact angle (WCA) measurements. The antimicrobial performance of the strains was evaluated using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. After treatment, the fabrics exhibited enhanced hydrophobic and antimicrobial properties, which was attributed to the presence of a micro-pleated structure and nanosilver. The modified textiles demonstrated a static WCA of approximately 154° and an impressive 99.99% inhibition rate against both test microbes. Notably, the WCA remained above 140° even after 500 washing cycles or 3000 friction cycles.

The corrosion resistance and antibacterial properties of fixed orthodontic devices are insufficient in the complex oral cavity, which delays tooth movement and causes enamel demineralization. To overcome the challenges, this research constructs a series of polydopamine-graphene oxide (PDA-GO) nanocoatings on representative NiTi archwires via self-assembly. The morphology, chemical structure, and multifunctional properties of coatings showed tunability dependent on the PDA/GO ratio. Optimized PDA-GO coatings with uniform and dense characteristics prolonged the diffusion path for the corrosive medium and reduced Ni dissolution in NiTi alloys. Meanwhile, the applied coatings endowed NiTi alloys with antibacterial activity against Streptococcus mutans due to the surface structures and inherent properties of PDA-GO. In vitro cytotoxicity tests further verified their good biocompatibility. This bio-inspired nanocomposite coating provides a practical reference for modification of dental metal surfaces to better behave in the intraoral environment.

Abstract With the increasing demand for multidirectional vibration measurements, traditional triaxial accelerometers cannot achieve vibration measurements with high sensitivity, high natural frequency, and low cross-sensitivity simultaneously. Moreover, for piezoresistive accelerometers, achieving pure axial deformation of the piezoresistive beam can greatly improve performance, but it requires the piezoresistive beam to be located in a specific position, which inevitably makes the design more complex and limits the performance improvement. Here, a monolithically integrated triaxial high-performance accelerometer with pure axial stress piezoresistive beams was designed, fabricated, and tested. By controlling synchronous displacements at both piezoresistive beam ends, the pure axial stress states of the piezoresistive beams could be easily achieved with position independence without tedious calculations. The measurement unit for the z-axis acceleration was innovatively designed as an interlocking proof mass structure to ensure a full Wheatstone bridge for sensitivity improvement. The pure axial stress state of the piezoresistive beams and low cross-sensitivity of all three units were verified by the finite element method (FEM). The triaxial accelerometer was fabricated and tested. Results showing extremely high sensitivities (x axis: 2.43 mV/g/5 V; y axis: 2.44 mv/g/5 V; z axis: 2.41 mV/g/5 V (without amplification by signal conditioning circuit)) and high natural frequencies (x/y axes: 11.4 kHz; z-axis: 13.2 kHz) were obtained. The approach of this paper makes it simple to design and obtain high-performance piezoresistive accelerometers.

Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for human hand, foot, and mouth disease (HFMD), which has threatened the health of young children, particularly in Asia-Pacific nations. Vaccination is an effective strategy for protecting children from CVA16 infection. However, there is currently no licensed CVA16 vaccine for use in humans. In this study, we isolated a high-growth CVA16 virus strain in MRC-5 cells and developed an MRC-5-adapted vaccine candidate strain termed CVA16-393 via two rounds of plaque purification. The CVA16-393 strain was grouped into the B1b subgenotype and grew to a titre of over 107 TCID50/ml in MRC-5 cells. The VP1 gene region of this strain, which contains the major neutralizing epitopes, displayed high stability during serial passages. The inactivated whole-virus vaccine produced by the CVA16-393 strain induced an effective neutralizing antibody response in Meriones unguiculatus (gerbils) after two doses of intraperitoneal inoculation. One week after the booster immunization, the geometric mean titres of the neutralizing antibodies for the 10246, 40812TXT, 11203SD, TJ-224 and CA16-194 strains from different regions of China were 137.8, 97.8, 113.4, 64.1 and 122.3, respectively. A CVA16 vaccine dose above 25 U was also able to provide 100% cross-protection against lethal challenges with these five clinical strains in gerbils. Immunization at a one-week interval could maintain a high level of neutralizing antibody titres for at least 8 weeks. Thus, the vaccine produced by this CVA16-393 strain might be promising.

BackgroundPrevious studies have identified a series of specific adverse pregnancy outcomes (APOs) linked with temperature extremes. Most of them focus on preterm birth, low birth weight, and stillbirth. Other possible adverse outcomes were under-researched. This study aimed to investigate the impact of ambient temperature on maternal complications, white blood cell count (WBC), newborn hearing, and neonatal jaundice.MethodsA total of 418 participants were recruited from Fuzhou Maternity & Child Healthcare Hospital in 2016. Participants were invited to fill out a structured questionnaire. The gridded near-surface air temperatures at a resolution of 0.1°* 0.1° for Fuzhou were extracted from a published dataset. Meteorological data and PM2.5 were extracted based on participants’ residential addresses using R packages “ncdf4” and “raster.” Multivariate logistic regression models were used to quantify the effects of ambient temperature on APOs after controlling for confounders.ResultsOverall, there were 107 APOs, accounting for 25.6% of all participants. Every 1°C increase in mean temperature was associated with a 10.0% increase in APOs (aOR = 1.100, 95%CI 1.006–1.203) during the period of early pregnancy. However, negative associations were observed in the middle pregnancy period, and a 1°C increase in mean temperature was associated 8.8% decrease in APOs (aOR = 0.912, 95%CI 0.846–0.982). Diurnal temperature variation had a significant impact on APOs in the third trimester. Infant jaundice was negatively associated with temperature exposure in the middle and late pregnancy periods. The risk of neonatal jaundice increased at lag weeks 2–9 in the first trimester, with the greatest lagged effect (aOR = 1.201, 95%CI 1.020–1.413) observed at lag week 3. A 1°C increase in mean temperature led to a 29.6% (aOR = 1.296, 95%CI 1.019–1.649) increase in high WBC. A 1°C increase in temperature variation was associated with more than two times (aOR = 2.469, 95%CI 1.001–6.089) increase of high WBC in the first trimester and about five times (aOR = 4.724, 95%CI 1.548–14.409) increase in the third trimester.ConclusionAmbient temperature affects neonatal jaundice, newborn hearing loss, and infections during pregnancy. In addition to the identified epidemiologic link and susceptible exposure windows, there is a need to understand the underlying biological mechanisms for better recommendations for climate change adaptation policies.

According to the controlled shear rate (CSR) test, the shear stiffening gel (SSG) exhibited viscoelastic behavior, which can be fully described by the general Maxwell model. A specific analytical model was established to identify the material parameters automatically based on simulated annealing (SA) optimization. Besides, according to the CSR tests under different temperatures, the influence of temperature and strain rate on the mechanical behavior of SSG was assumed to be decoupled. And an applicable engineering relation was introduced for parameter adjustment of the Maxwell model near room temperature. The reliability of the material parameters was verified through the results comparison of the low-speed impact tests of SSG and corresponding FE simulations.Based on field analysis of the FE simulations, the mechanism of the stress dispersion ability of SSG was elaborated. A feasible design idea was introduced to fully utilize this property. In order to verify the effectiveness of the design idea, a series of egg impact tests were developed, conducted, and analyzed. And the protective idea proved helpful in fully invoking the stress dispersion potential of SSG assembly for impact protection and improving the lightweight design.

Abstract Background Milk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas. Objectives To evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months. Methods In a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months. Results Infants (n = 375) completed the study with average dropout of

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by inflammation and demyelination. Presently, repeated relapses of MS necessitate long-term immune-regulatory therapy. Blocking the CD28-B7 and CD40-CD40L costimulatory pathways is an effective and synergistic method for the prevention and amelioration of clinical symptoms of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. In this study, to explore the efficacy and safety of MS gene therapy, we used adeno-associated virus (AAV) as a vector to deliver CTLA4-immunoglobulin (Ig) or CD40-Ig on the EAE induced by myelin oligodendrocyte glycoprotein (MOG). Our results showed that a single administration of AAV8-CTLA4-Ig, either alone or with AAV8-CD40-Ig, protected mice from EAE and reversed disease progression. Decreased CD4+ and CD8+ T cell infiltration, inhibition of MOG antibody response, and downregulation of neuroinflammation were observed in mice receiving AAV, suggesting that autoimmunity was suppressed in EAE pathology. Moreover, no hematological or hepatic toxicity was observed in AAV-treated mice. Thus, compared with treatment with recombinant CTLA4-Ig (belatacept), AAV gene therapy could effectively control clinical symptoms and suppress autoimmunity in the long term. In summary, our study provides a potential therapeutic method for blocking T cell costimulation for the treatment of MS via gene therapy.

ObjectHospital sewage have been associated with incorporation of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) into microbes, which is considered as a key indicator for the spread of antimicrobial resistance (AMR). The compositions of dental waste water (DWW) contain heavy metals, the evolution of AMR and its effects on the water environment in the context of heavy metal environment have not been seriously investigated. Thus, our major aims were to elucidate the evolution of AMR in DWW.MethodsDWW samples were collected from a major dental department. The presence of microbial communities, ARGs, and MGEs in untreated and treated (by filter membrane and ozone) samples were analyzed using metagenomics and bioinformatic methods.ResultsDWW-associated resistomes included 1,208 types of ARGs, belonging to 29 antibiotic types/subtypes. The most abundant types/subtypes were ARGs of multidrug resistance and of antibiotics that were frequently used in the clinical practice. Pseudomonas putida, Pseudomonas aeruginosa, Chryseobacterium indologenes, Sphingomonas laterariae were the main bacteria which hosted these ARGs. Mobilomes in DWW consisted of 93 MGE subtypes which belonged to 8 MGE types. Transposases were the most frequently detected MGEs which formed networks of communications. For example, ISCrsp1 and tnpA.5/4/11 were the main transposases located in the central hubs of a network. These significant associations between ARGs and MGEs revealed the strong potential of ARGs transmission towards development of antimicrobial-resistant (AMR) bacteria. On the other hand, treatment of DWW using membranes and ozone was only effective in removing minor species of bacteria and types of ARGs and MGEs.ConclusionDWW contained abundant ARGs, and MGEs, which contributed to the occurrence and spread of AMR bacteria. Consequently, DWW would seriously increase environmental health concerns which may be different but have been well-documented from hospital waste waters.

Background and AimThe prediction models of postoperative survival for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) have not been well established. The study objective was the development of nomograms to predict disease recurrence and overall survival (OS) in these patients.MethodsData were obtained from 1046 HBV-related MVI-positive HCC patients who had undergone curative resection from January 2014 to December 2017. The study was approved by the Eastern Hepatobiliary Surgery Hospital and Jinling Hospital ethics committee, and patients provided informed consent for the use of their data. Nomograms for recurrence and OS were created by Cox regression model in the training cohort (n=530). The modes were verified in an internal validation cohort (n= 265) and an external validation cohort (n= 251).ResultsThe nomograms of recurrence and OS based on preoperative serological indicators (HBV-DNA, neutrophil-lymphocyte ratio, a-fetoprotein), tumor clinicopathologic features (diameter, number), surgical margin and postoperative adjuvant TACE achieved high C-indexes of 0.722 (95% confidence interval [CI], 0.711-0.732) and 0.759 (95% CI, 0.747-0.771) in the training cohort, respectively, which were significantly higher than conventional HCC staging systems (BCLC, CNLC, HKLC).The nomograms were validated in the internal validation cohort (0.747 for recurrence, 0.758 for OS) and external validation cohort(0.719 for recurrence, 0.714 for OS) had well-fitted calibration curves. Our nomograms accurately stratified patients with HBV-HCC with MVI into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. Prediction models for recurrence-free survival (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-RFS/) and OS (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-OS/) were constructed.ConclusionsThe two nomograms showed good predictive performance and accurately distinguished different recurrence and OS by the nomograms scores for HBV-HCC patients with MVI after resection.

A novel hybrid framework of optimized deep learning models combined with multi-sensor fusion is developed for condition diagnosis of concrete arch beam. The vibration responses of structure are first processed by principal component analysis for dimensionality reduction and noise elimination. Then, the deep network based on stacked autoencoders (SAE) is established at each sensor for initial condition diagnosis, where extracted principal components and corresponding condition categories are inputs and output, respectively. To enhance diagnostic accuracy of proposed deep SAE, an enhanced whale optimization algorithm is proposed to optimize network meta-parameters. Eventually, Dempster-Shafer fusion algorithm is employed to combine initial diagnosis results from each sensor to make a final diagnosis. A miniature structural component of Sydney Harbour Bridge with artificial multiple progressive damages is tested in laboratory. The results demonstrate that the proposed method can detect structural damage accurately, even under the condition of limited sensors and high levels of uncertainties.

ObjectiveTo explore the influence of the type of anterior clinoidal meningioma on surgical strategy planning, surgical approach selection, and postoperative efficacy.Patients and methodsWe conducted a retrospective analysis of the clinical data of 63 cases, including data on visual function, extent of tumor resection, and postoperative follow-up. Grade I and II approaches were selected according to the type of tumor. A univariate analysis of the factors influencing the extent of tumor resection, postoperative visual function, and postoperative relapse and complications was conducted.ResultsSimpson Grade I–II total resection was seen in 48 cases (76.2%), with an overall relapse/progression rate of 12.7%. The tumor type and texture and the relationship between the tumors and adjacent structures were the main factors influencing total tumor resection (P < 0.01). The overall postoperative visual acuity improvement, stabilization rate, and deterioration rate were 76.2, 15.9, and 7.9%, respectively. Postoperative visual acuity level was significantly correlated with preoperative visual acuity level and tumor type (P < 0.01).ConclusionsDetermining the type of tumor at a preoperative level and whether the optic canal and cavernous sinus are invaded can aid in the planning of detailed individualized surgical strategies.

Objectives: Hip inflammation is one of the most common complications in patients with spondyloarthritis (SpA). Herein, we employed use of a deep learning-based magnetic resonance imaging (MRI) evaluation model to identify irregular and multiple inflammatory lesions of the hip.Methods: All of the SpA patients were enrolled at the Xijing Hospital. The erythrocyte sediment rate (ESR), C-reactive protein (CRP), hip function Harris score, and disease activity were evaluated by clinicians. Manual MRI annotations including bone marrow edema (BME) and effusion/synovitis, and a hip MRI scoring system (HIMRISS) assessment was performed by experienced musculoskeletal radiologists. The segmentation accuracies of four deep learning models, including U-Net, UNet++, Attention-Unet, and HRNet, were compared using five-fold cross-validation. The clinical agreement of U-Net was evaluated with clinical symptoms and HIMRISS results.Results: A total of 1945 MRI slices of STIR/T2WI sequences were obtained from 195 SpA patients with hip involvement. After the five-fold cross-validation, U-Net achieved an average segmentation accuracy of 88.48% for the femoral head and 69.36% for inflammatory lesions, which are higher than those obtained by the other three models. The UNet-score, which was calculated based on the same MRI slices as HIMRISS, was significantly correlated with the HIMRISS scores and disease activity indexes (p values

Abstract Immune checkpoint molecules are promising anticancer targets, among which therapeutic antibodies targeting the PD-1/PD-L1 pathway have been widely applied to cancer treatment in clinical practice and have great potential. However, this treatment is greatly limited by its low response rates in certain cancers, lack of known biomarkers, immune-related toxicity, innate and acquired drug resistance, etc. Overcoming these limitations would significantly expand the anticancer applications of PD-1/PD-L1 blockade and improve the response rate and survival time of cancer patients. In the present review, we first illustrate the biological mechanisms of the PD-1/PD-L1 immune checkpoints and their role in the healthy immune system as well as in the tumor microenvironment (TME). The PD-1/PD-L1 pathway inhibits the anticancer effect of T cells in the TME, which in turn regulates the expression levels of PD-1 and PD-L1 through multiple mechanisms. Several strategies have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including combination therapy with other standard treatments, such as chemotherapy, radiotherapy, targeted therapy, anti-angiogenic therapy, other immunotherapies and even diet control. Downregulation of PD-L1 expression in the TME via pharmacological or gene regulation methods improves the efficacy of anti-PD-1/PD-L1 treatment. Surprisingly, recent preclinical studies have shown that upregulation of PD-L1 in the TME also improves the response and efficacy of immune checkpoint blockade. Immunotherapy is a promising anticancer strategy that provides novel insight into clinical applications. This review aims to guide the development of more effective and less toxic anti-PD-1/PD-L1 immunotherapies.

The Li intercalation reaction exhibits non-uniform behavior along the thickness direction of the electrode in a Li-ion battery. This non-uniformity, or intra-layer inhomogeneity (ILIH), becomes more serious as the charging and discharging speed increases. Substantial ILIH can lead to Li plating and the emergence of inhomogeneous inner stress, resulting in a decrease in battery service life and an increase in battery safety risks. In this study, an operando optical observation was conducted based on the color change reaction during Li intercalation in the anode. Subsequently, we introduce a novel quantitative method to assess ILIH in commercial Li-ion batteries. A specific ILIH value (KILIH) is first used in this article for ILIH characterization. An analysis of KILIH at different charging and discharging rates was conducted, alongside the exploration of KILIH-SOC trends and their underlying mechanisms. The proposed method exhibits favorable mathematical convergence and physical interpretability, as supported by the results and mechanism analysis. By enabling the assessment of ILIH evolution in response to SOC and (dis)charging rate variations, the proposed method holds significant potential for optimizing fast charging protocols in commercial batteries and contributing to the development of refined electrochemical battery models in future research.

Expansion-break connecting rods are high-end products for automotive precision transmission. They need to have high strength, high toughness, and brittle cleavage fracture characteristics during cracking processing. Continuous casting production of nonquenched and tempered steel for high-carbon, sulfur-containing, free-cutting, and expanding connecting rods is the current trend for efficient production. Based on the typical bloom continuous casting process and analysis of the as-cast structure and composition uniformity, the common unqualified fracture morphology due to as-cast hereditary factors were studied. Taking the typical German C70S6 steel as an example, a 250 mm × 280 mm section-curved continuous caster was adopted to study the as-cast macrostructure and dendrite morphology of the bloom casting with popular mold electromagnetic stirring. Moreover, the chemical distribution at different crystal regions was studied. Results show that the common center shrinkage defects of high-carbon steel continuous casting blooms are under control, which are beneficial to improve the qualified rate of internal flaw detection for their subsequent hot-rolled bars. However, it is found that there are obvious negative segregation white bands of carbon and sulfur and the deflection of columnar crystals in the solidification front of the initial solidified shell. Both the image analysis of the metallographic sample and solidification simulation by a phase-field method show that this columnar crystal has countercurrent growth characteristics. In addition, its deflection angle is the result of the primary dendrite tip growing in the opposite direction to the swirling fluid flow. In the center of the narrow surface, the measured primary dendrite deflection angle of the columnar crystal region is between −7° and 27°. EDS was used to further detect the distribution of the main alloying elements Si, Mn, and Mo in the different crystal regions of the bloom casting, revealing the segregation characteristics of the as-cast product and differences of each solute element. Finally, the heredity of this as-cast structure and composition segregation on the structure of subsequent hot-rolled bars and connecting rods was discussed. Moreover, the influence of the fracture inconsistency of its expansion and fracture processing were explored. It is pointed out that the as-cast quality control from the very beginning of casting has special significance in meeting the requirement of both processing and service properties of these high-grade high strength low alloy steels.