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Abstract Purpose This study aimed to evaluate the outcomes of Pelnac assisted by vacuum sealing drainage in managing severe avulsion injuries of the fingers. Methods This prospective study was conducted from May 2017 to September 2023, involving 12 consecutive patients with severe avulsion injuries of the fingers. Patients underwent single-stage or two-stage procedures employing Pelnac assisted by vacuum sealing drainage (VSD) for the management of severe avulsion injuries of the fingers. Post-operative follow-up was routinely scheduled, and aesthetic and functional outcomes, sensory recovery, complications were recorded. Results Twelve patients were included in the analysis, consisting of 9 males and 3 females, with a mean age of 30.6 ± 11.0 years. All patients presented with severe damage to tendons and deep tissues, as well as varying degrees of bone exposure and injury, with average defect area of 36.9 cm² (range, 11 to 180 cm²). At the final follow-up (mean, 14 months; range, 12 to 29 months), the average score on the Fingertip Injuries Outcome Score (FIOS) was 14.3 (SD 3.9, range 10 to 22), with 6 patients achieving excellent result, 4 classified as good and 2 as fair. Patients reported an average satisfaction score of 74.0 (SD 11.6; range 51 to 94) regarding the aesthetic appearance. The average score on the Vancouver Scar Scale score was 2.3 (SD 2.1, range 1.0 to 7.4). Ten patients reported normal or near-normal sensation, while 2 patients experienced slight sensory loss. The average score on the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was 13.2 (SD 8.5, range 0 to 47). No infections or hematomas were reported during hospitalization or after discharge. Conclusion Pelnac, assisted by VSD, proved to be an effective approach for managing severe avulsion injuries of the fingers. This approach can be considered as a viable alternative for addressing severe injuries or complex wound conditions.

Accurate and reliable precipitation forecasting is vital for effective water resource management and disaster mitigation, especially in geographically diverse and climatically complex regions like China. This study proposes an advanced methodology for medium- and long-term hydrological forecasting by integrating multiple machine learning models through a modified stacking ensemble strategy (MSES). We developed and compared five deterministic precipitation forecasting models, including elastic net regression (ENR), support vector regression, random forest, extreme gradient boosting, and light gradient boosting to provide forecasts with lead times ranging from 0 to 5 months at a spatial resolution of 0.5$^\circ$. The MSES was then evaluated against the traditional Bayesian model averaging (BMA) approach. Our comprehensive evaluation, based on deterministic forecasting metrics such as the anomaly correlation coefficient (ACC), mean squared skill score (MSSS), and Graded Precipitation Score (Pg), demonstrated the MSES outperformed individual models and the BMA method. The MSES achieved ACC scores between 0.6 and 0.9 for lead time (LT) $= 0$ month, with an average of around 0.8 for LT $= 2$ months. The MSSS for MSES was above 0.5 in more than half of the evaluations, and the Pg score was consistently above 80, indicating high accuracy in precipitation magnitude prediction. These findings highlight the promise of advanced machine learning strategies like MSES in improving the accuracy and robustness of precipitation forecasts, addressing critical needs in water resource management and disaster mitigation in China.

Abstract Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and their heterogeneity can impact the immune environment, which may be the cause of the good outcomes of MSCs-based therapy that cannot always be achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed great potential in inflammatory and autoimmune diseases due to their immature properties compared with MSCs. In our study, single-cell RNA sequencing (scRNA-seq) revealed that SHED in a low differentiation state (S7) exhibited the powerful ability to recruit multiple immune cells. In contrast, SHED in a relatively high differentiation state (S1) may hold a solid ability to secret many factors with paracrine signaling capacity. The analysis result shows that SHED has more robust immunomodulatory properties than human bone marrow-derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs). When co-cultured with PBMCs, SHED can enhance the proliferation of Treg and down-regulate TNF-α in vitro. SHED may have some advantages in the treatment of inflammatory and autoimmune diseases.

Abstract Background Bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) represent a significant disease burden worldwide. However, a comprehensive analysis of the mortality rates and global epidemiology across different ARB species associated with BSIs is currently lacking. Methods We conducted a systematic review by searching multiple databases (PubMed, Web of Science, and Embase) for studies reporting ARB-related BSIs data up to June 19, 2023. Additionally, we performed genomic analyses of all the publicly available bacterial genomes associated with BSIs to elucidate their molecular characteristics. Results A total of 322 articles (N = 90,672 patients) were included in this study. For 28 or 30-day mortality, the overall mortality rate for all ARB species was 32.0%. Among them, antibiotic-resistant A. baumannii exhibited the highest rate (54.2%). And the top three ARB types with the highest mortality rates at 28 or 30-day were CefeR-PA (cefepime-resistant P. aeruginosa), CREC (carbapenem-resistant E. coli), and CRAB (carbapenem-resistant A. baumannii), all exceeding 50%, whereas the mortality rates of CRKP (carbapenem-resistant K. pneumoniae), CRPA (carbapenem-resistant P. aeruginosa), and VREfm (vancomycin-resistant E. faecium) were at least 40%. A total of 9,289 ARB genomes related to BSIs were acquired from the NPDIB database and are predominantly distributed in North America, Asia, and Europe. Antibiotic resistance gene (ARG) analysis identified a total of 613 ARG subtypes from the top six ARB species, with numbers ranging from 48 for E. faecium to 253 for K. pneumoniae. Furthermore, specific clones of ARB species were strongly associated with BSIs, such as ST131 in E. coli, ST8, and ST5 in S. aureus, ST2 in A. baumannii, and ST11 and ST258 in K. pneumoniae. Conclusion ARB contributed to the burden of BSIs, with a 30-day all-cause mortality rate as high as 32.0%. ARB strains causing BSIs display high genetic diversity, highlighting the importance of continuing to monitor high-risk clones to control the development of antibiotic resistance. Differences in ARGs patterns require tailored antibiotic management strategies for each ARB species.

Hot stamping steels are extensively used in the production of lightweight automobile bodies, which are crucial for reducing carbon emissions. Although significant advancements have been made in the development of Si–Cr alloyed uncoated hot stamping steels to mitigate high-temperature oxidation, a gap remains in the literature regarding Al–Si alloyed uncoated steels. Specifically, there is a need for systematic investigation into their oxidation resistance. In this study, we designed Al–Si alloyed uncoated hot stamping steels based on the 22MnB5 composition system and characterized the scales formed under a simulated hot stamping thermal cycle. Our results indicate that the formation of dense Al2O3, SiO2, and Fe2SiO4 phases, driven by the presence of Al and Si, inhibits FeO formation, thereby enhancing oxidation resistance. Notably, the scale thickness decreases with increasing Al content, reaching just 3.5 μm at 0.48% Al, which is substantially lower than the 46 μm observed in 22MnB5 steel. However, due to compressive stress in the scale during its growth process, oxide ridges form when the Al content exceeds approximately 0.1%. Therefore, maintaining an optimal Al content of around 0.1% is recommended to prevent the formation of oxide ridges and prolong the lifespan of hot stamping moulds. This research not only addresses a critical gap in the literature but also offers a cost-effective strategy for enhancing the oxidation resistance of hot stamping steels, contributing to the broader goals of lightweight vehicle design and carbon emission reduction.

This study investigates the hot deformation behavior, microstructural evolution, and processing map of a high-carbon high-strength low alloy steel subjected to hot compression tests in the temperature range of 850 °C–1150 °C and strain rates from 0.01 s⁻1–10 s⁻1. A highly accurate flow stress constitutive equation has been established and the activation energy of the experiment steel is 462.6 kJ/mol. Processing maps were generated to identify unstable zones, low-power dissipation zones, and optimum processing zones, accompanied by detailed discussions on corresponding microstructures and mechanical properties. The recommended hot deformation parameters at a true strain of 0.9 are temperatures from 944 °C to 1050 °C and strain rates from 0.01 s⁻1 to 0.52 s⁻1 according to the processing map. The effects of deformation temperature and strain rate on the microstructure were then investigated. It is revealed that reducing deformation temperature and increasing strain suppress the recrystallization process and the growth of recrystallized grains; while VC precipitation is suppressed under high temperatures and high strain rates.

The strength enhancement usually increases its susceptibility to hydrogen (H) embrittlement in steel materials. However, the atomic-level mechanisms of solutes influence hydrogen behavior at grain boundaries (GBs) remain incompletely understood. To address this gap, first-principles calculation was utilized to analyze the interactions between 25 different solutes and H at the Σ5 (310) GB of body-centered cubic (BCC) iron. This study focused on how these solutes affect H segregation and their role in mitigating H-induced GB embrittlement, thereby elucidating the mechanisms of solute-H interactions at GBs. The results show that elements such as Cr, Mn, Ni, Zr, Nb, Mo, W, and Re not only reduce H segregation at GBs, but also effectively alleviate H-induced GB embrittlement. Furthermore, first-principles calculation tensile tests (FPCTT) simulations were employed to investigate the effect of the H segregation behavior at GB on uniaxial tensile strain, shedding light on the fundamental processes of bond break and crack initiation at GBs. The present work provides deeper insights into the mechanisms of GB embrittlement and offers strategic guidance for designing steel materials with enhanced H embrittlement resistance.

The present study investigated the impact of 20–80 ppm Nb on the microstructure and properties of hypereutectoid pearlite steel. Remarkably, even trace amounts of Nb exhibited a favorable effect on the refinement of austenite grain. The addition of the Nb element resulted in a reduction of pearlite transition temperature, leading to a decrease of approximately 13% in lamellar spacing and 11% in the size of pearlite colonies. Furthermore, the dragging effect of the Nb element on the carbon atoms in hypereutectoid steel facilitated the control and refinement of network carbides. These findings offer valuable theoretical guidance for the production of ultra-high-strength wire rods. When the Nb content reached 80 ppm, it promoted the precipitation of (Ti, V)C, while simultaneously improving the morphology of square carbides. The grain refining strengthening mechanism accounted for about 70% of the overall strengthening effect observed in high carbon wire rods, with the influence of the Nb element primarily targeting grain refinement. Consequently, the incorporation of minute quantities of Nb presents a promising avenue for the development of ultra-high-strength hypereutectoid wire rods, offering significant potential for enhancing their strength properties.

In this paper, the influence of decreasing Zr content (0.0110 wt%, 0.0044 wt%) on the microstructure, MnS inclusion characteristics, and mechanical properties of medium carbon ferrite-pearlite steel was studied. The results show that the volume fraction of intragranular ferrite (IGF) in steel increases with a reduction in Zr content. The ductility of the steel is reduced by 1.83%, the impact toughness is increased by 2.5 times, and the yield strength is almost unchanged. Compound MnS inclusions are the main inclusions that induce IGF formation. The proportion of heterogeneous nucleation of MnS inclusions using oxides as nucleation sites is increased, which is the main reason for the increase in the volume fraction of IGF. Furthermore, MnS inclusions change from type Ⅲ to type Ⅰ and Ⅱ, and their distribution is gradually uniform. Thermodynamic analysis reveals that the underlying cause for the morphological transformation of MnS inclusions is the rapid surge in the supersaturation of S element in molten steel. The presence of liquid-phase low-melting inclusions (MnS–Al2O3) promotes the formation of type Ⅰ MnS inclusions. The volume fraction and the dimension perpendicular to the fracture surface of the MnS inclusions are increased by at least 33% and 111%, while their aspect ratio is reduced by a maximum of up to 19%. The change in the volume fraction of MnS inclusions is the primary factor contributing to the decrease of tensile plasticity. The toughness of steel is mainly affected by the aspect ratio and the dimension perpendicular to the fracture surface of MnS inclusions.

Abstract In recent years, the Integrated Satellite Aerial Terrestrial (I‐SAT) network has garnered significant attention as an innovative and integrated communication system. However, it still encounters interference in the face of the complex external environment. In this context, reconfigurable intelligent surface (RIS) provides a key way of solving this problem and effectively improves the performance and stability of the I‐SAT network. This article considers the combination of unmanned aerial vehicle (UAV) and RIS and proposes a novel architecture for sub‐connected active RIS (ARIS) under the energy consumption constraints of UAV and ARIS. The authors first provide a UAV‐ARIS based position prediction strategy for the vehicle. Then, a joint RIS phase shift, amplification and UAV trail optimization algorithm is proposed to pursue a high achievable rate. The interference between each link and the total energy consumption are all taken into consideration. In addition, a deep deterministic policy gradient (DDPG) algorithm is utilized for the optimization problem, and achieves convergence in continuous action space. Finally, the simulation results affirm the precision of the proposed method in significantly enhancing performance compared to other schemes.

Nowadays, high-strength press-hardened steels (PHS) have gained wide applications in automotive body-in-white owing to excellent mechanical properties. Nevertheless, the fatigue properties of high-strength PHS and associated failure mechanisms have not been clearly revealed, which restricts their potential applications in other parts of automobiles involving fluctuating and repetitive stresses, such as wheels or beams. In this work, the fatigue behavior of 1900 and 2000 MPa grade PHS is systematically studied, with the main focus on the associated deformation and fatigue cracking mechanisms. The fatigue behavior of these two steels is similar, and the ratio of fatigue strength to tensile strength is around 0.5. The fatigue damage mechanism of high-strength PHS is dominated by surface cracking, as the fine martensite structures reduce the stress concentration and cracking at small-sized inclusions. This work can provide guidance for the application of high-strength PHS in alternating loads scenarios.

Aluminum alloys are extensively utilized in the transportation and aerospace industries due to their excellent processability and corrosion resistance. A key aspect affecting the application of aluminum alloys is fatigue failure, with fatigue strength constituting an essential indicator for assessing the failure mode. In this study, 859 data sets were collected to evaluate the effects of aluminum alloy composition and mechanical properties on fatigue strength. To comprehensively evaluate the features that exert a great influence on the fatigue strength of wrought aluminum alloys, atomic physical quantities of aluminum alloys were added to the original data set. To improve the computational efficiency and physical interpretability of the model, Spearman correlation analysis, optimal subset method, and other methods were used to perform feature selection on the atomic feature quantities and mechanical properties in the data set. Finally, a mathematical relationship between material descriptors and fatigue strength was established based on the alloy composition and the three most relevant features in the feature screening, which helps to better understand and predict the fatigue behavior of wrought aluminum alloys.

This work presents an integrated multi-quantum well (MQW) optoelectronic sensor leveraging III-nitride materials for multifunctionality on a monolithic chip. The sensor was fabricated using standard microfabrication techniques and adopted the identical InGaN/GaN MQWs, which enables simultaneous emission and detection. The sensor is featured with a double concentric circle structure which supports both on-chip and off-chip detection mechanisms, being capable of detecting environmental parameters like rotational speed, proximity, and sucrose concentration. It exhibits stable photocurrent response to rotational speed up to 8000 rpm, a 3 cm vertical detection range, and a linear response with 3.9 nA/% sensitivity to changes in sucrose concentration, which demonstrates the potential for diverse applications in industrial and biomedical fields.

Oncolytic virotherapy in combination with immunotherapy has demonstrated significant survival benefits in some types of cancer. Here, we summarized the development, research hotpots and potential trends of the combination therapy using visual bibliometric analysis. A total of 712 articles were retrieved on June 21, 2023. The USA was the top contributors of any country (325, 45.65%), and the Rluk Research Libraries UK ranked first (43, 6.03%) of any institutions. The Journal for ImmunoTherapy of Cancer was with the largest publications (60, 8.43%). ‘Tumor microenvironment’ and ‘delivery’ were citation keywords with the strongest ongoing bursts. Research fronts in the future may focus on the methods of virus delivery and tumor microenvironment modulation. Futhermore, the most extensively studied cancer were melanoma, glioma and hepatocellular carcinoma.

Abstract The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin–eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

Abstract Background Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. Methods This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. Results Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. Conclusions Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Context information is significant for semantic extraction and recovery of messages in semantic communication. However, context information is not fully utilized in the existing semantic communication systems since relationships between sentences are often ignored. In this paper, we propose an Extended Context-based Semantic Communication (ECSC) system for text transmission, in which context information within and between sentences is explored for semantic representation and recovery. At the encoder, self-attention and segment-level relative attention are used to extract context information within and between sentences, respectively. In addition, a gate mechanism is adopted at the encoder to incorporate the context information from different ranges. At the decoder, Transformer-XL is introduced to obtain more semantic information from the historical communication processes for semantic recovery. Simulation results show the effectiveness of our proposed model in improving the semantic accuracy between transmitted and recovered messages under various channel conditions.

Increasing research has focused on semantic communication, the goal of which is to convey accurately the meaning instead of transmitting symbols from the sender to the receiver. In this paper, we design a novel encoding and decoding semantic communication framework, which adopts the semantic information and the contextual correlations between items to optimize the performance of a communication system over various channels. On the sender side, the average semantic loss caused by the wrong detection is defined, and a semantic source encoding strategy is developed to minimize the average semantic loss. To further improve communication reliability, a decoding strategy that utilizes the semantic and the context information to recover messages is proposed in the receiver. Extensive simulation results validate the superior performance of our strategies over state-of-the-art semantic coding and decoding policies on different communication channels.

To overcome the strength-ductility conflict in particle reinforced aluminum matrix composites (PRAMCs), a novel dual configuration strategy of microstructure was proposed in this work. The dual configuration including both heterogeneous grain structure and hybrid reinforcements was obtained by powder metallurgy, which was designed as submicron-sized SiC particles (SiCsm)/Al and micron-sized SiC particles (SiCm)/2024Al components. Representative alternating coarse grain (CG) bands containing SiCm and ultra fine grain (UFG) bands with dispersed SiCsm were revealed in microstructural characterizations. Compared to corresponding homogeneous composites with the same fraction particles, the dual configuration composite achieved simultaneous enhancement in strength and ductility and remained a comparable Young’s modulus of 98GPa, which represented 442 MPa in yield strength, 590 MPa in ultimate strength and 8.7 % in fracture elongation. The extra strength provided by hetero-deformation induced (HDI) strengthening is a potential dominant strengthening mechanism. The intrinsic toughening mechanisms primarily contribute to HDI strain hardening and enhanced dislocation accumulation capacity, while the extrinsic toughening mechanisms presumably attribute to more uniform microcrack distribution and blunting effect of CG zones on cracks. Our work provides a feasible route including ball milling and powder assembly to preparate high-modulus aluminum matrix composites for strength-ductility balance design.

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multi-disciplinary team (MDT) and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.

Many studies have reported the toxic effects of microplastics (MPs) on organisms, especially on how conventional plastics affect organisms after short-term exposure. The effects of biodegradable plastics on organisms are, however, largely unexplored, especially concerning their impact after long-term exposure. We perform a series of experiments to examine the effects of conventional (polyethylene (PE)) and biodegradable (polylactic acid (PLA)) microplastics on earthworms at three concentrations (0.5 %, 2 %, and 5 % (w/w)) and particle sizes (149, 28, and 13 μm) over short- (14 d) and long-term (28 d) periods of exposure. Negative effects on earthworms are more pronounced following exposure to PE than PLA, particularly over the shorter term. After longer-term exposure, earthworms may adapt to PE and PLA environments. A close relationship exists between the effects of MPs on earthworms and activities of superoxide dismutase, catalase, and malondialdehyde enzymes, which we use to evaluate the degree of antioxidant damage. We report both PE and PLA to negatively affect earthworms, but for the effects of PLA to be less severe after longer-term exposure. Further investigation is required to more fully assess the potential negative effects of PLA use on soil organisms in agriculture.

To observe the deformation and the failure process of solid objects in explosion and impact simulations, the clarity and accuracy of simulation image representations should be ensured. However, in the results of three-dimensional (3D) explosion field rendering, surface confusion and blurred images of the microstructure often lead to misunderstandings of the simulation results. In this work, based on the ray casting method and the Blinn–Phong lighting model, a volume rendering method is proposed that can adapt to the characteristics of step changes in the explosion field data and satisfies the requirements of observing the microstructure. The Blinn–Phong lighting model is applied to the light and shade calculation of the resampling point, and the gradient of the resampling point is obtained via interpolation calculations; then, it is normalized to obtain the normal vector. Finally, the opacity of the resampling point and the associated material color are substituted into the ray casting synthesis formula. In addition, several groups of examples of visual effects are analyzed from the subjective point of view of human visual effects and the objective points of view of image entropy, the mean gradient, image mean, and standard deviation. The results show that the new method addresses the problem of interface color confusion, improves the accuracy of microstructure rendering in solid media, increases the spatial sense of visual images, and satisfies the visualization requirements for explosion products and shock waves. At the same time, this approach effectively shortens the time for volume rendering of the explosion field.

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).

Abstract A surface acoustic wave (SAW) gyroscope measures the rate of rotational angular velocity by exploiting a phenomenon known as the SAW gyroscope effect. Such a gyroscope is a great candidate for application in harsh environments because of the simplification of the suspension vibration mechanism necessary for traditional microelectromechanical system (MEMS) gyroscopes. Here, for the first time, we propose a novel toroidal standing-wave-mode SAW gyroscope using focused interdigitated transducers (FIDTs). Unlike traditional SAW gyroscopes that use linear IDTs to generate surface acoustic waves, which cause beam deflection and result in energy dissipation, this study uses FIDTs to concentrate the SAW energy based on structural features, resulting in better focusing performance and increased SAW amplitude. The experimental results reveal that the sensitivity of the structure is 1.51 µV/(°/s), and the bias instability is 0.77°/s, which are improved by an order of magnitude compared to those of a traditional SAW gyroscope. Thus, the FIDT component can enhance the performance of the SAW gyroscope, demonstrating its superiority for angular velocity measurements. This work provides new insights into improving the sensitivity and performance of SAW gyroscopes.

The Hudson Oilfield’s Donghe sandstone reservoir has multiple independent oil–water systems. The complex oil–water relationship is mainly due to reservoir heterogeneity, especially the sealing and shielding effects of interlayers. This paper uses methods like well logging and test well data interpretation, seismic impedance inversion, and the simulation of oil and gas preferential migration paths. It analyzes and quantifies parameters related to sand layer oil content, physical properties, and the development degree of interbedded layers using small layers as units. Sandstone horizontal transportability has three types. Type I matches structural forms to form preferential migration paths. Type II transportability has enclosed sand bodies that obstruct oil and gas flow and change their migration paths. Unevenly distributed calcareous interbedded layers are the main controlling factor for vertical sand body transportability. Locally continuous cemented calcareous interbedded layers can form the base of a dome-shaped pinch-out lithologic trap in sandstone. The closure area of the trap is controlled by the pinch-out line of sandstone and the distribution of continuous interbedded layers together.

In our previous study, the ultrasound-assisted enzymatic extract of Platanus acerifolia leaves (PAL) was confirmed as an efficient corrosion inhibitor of steel. In this study, a new strategy-ultrafiltration-was proposed to further enhance the corrosion inhibition effect of this green steel corrosion inhibitor. To pinpoint the main players in the corrosion-inhibiting performance, the active compounds of the treated PAL extract were further quantitatively characterized via high performance liquid chromatography (HPLC). Electrochemical approaches were employed to investigate the anti-corrosion behavior. The adsorption film and surface morphology of the steel surface were characterized via X-ray photoelectron spectroscopy (XPS) and scanning electron microscope with energy dispersive spectrometer (SEM-EDS), respectively. Furthermore, simulations were carried out to further explore the inhibition mechanisms of the active molecules. The results showed that ultrafiltration significantly removed the polysaccharide impurities, thereby further concentrating the inhibition constituents. Twelve flavonoids and their derivatives were quantitatively traced, among which the procyanidins was the most pronounced ingredient (220 ppm). Ultrafiltration can effectively improve the inhibition performance of the extract. In the presence of chloride ions, the inhibition efficiency of the 1.5 wt% two-step processed extract was equivalent to that of the 5 wt% primary extract. Plus, SEM-EDS observations confirmed that the two-step processed extract was able to effectively mitigate the corrosion degree. XPS and simulation analyses revealed that the flavonoids and their derivatives executed the corrosion inhibition performance by forming a protective carbon-containing organic film on the steel surface via chelation and surface physical adsorption.

Persistent organic pollutants (POPs) and heavy metals in marine systems have been given more and more attention due to their high toxicity and bioaccumulation capacity. After discharging into the marine systems, large proportions of POPs and heavy metals are likely to remain in coastal seas, causing serious contamination and high ecological risks. However, the lack of systematic studies restricts our understanding of POP and heavy metal cycling in coastal regions. Herein, the coastal regions along the Chinese Bohai Sea (an important fishing and typically polluted area) were chosen to establish a study model for investigating long-term spatial–temporal variations, risk assessments, and controlling factors of hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), polycyclic aromatic hydrocarbons (PAHs), and heavy metals in coastal regions. The results showed that concentrations of HCHs, DDTs, and PAHs in sediment, and contents of heavy metals in seawater and sediment were higher than those in other coastal regions during 2015–2018 and that concentrations of As and Cu in approximately 95% and 20% of sampled organisms exceeded maximum permissible levels recommended by China and the WHO, respectively. The significantly temporal variations in HCH and PAH concentrations were indicative of increasing POP pollution, and no significantly temporal variations in most heavy metal concentrations were found. Meanwhile, the higher concentrations of POPs and heavy metals were mainly located in estuaries and other nearshore areas. The geo-accumulation index (Igeo), potential ecological risk index (PERI), and provisional tolerable daily intake (PTDI) showed that As, Cd and Hg should be listed as the primary heavy metal pollutants in sediment; higher dietary risk was posed by As through seafood consumption; the dietary risks posed by HCHs, DDTs, and PAHs were lower. Finally, the results of multiple regression, Pearson’s, and cluster analyses indicated that anthropogenic activities (e.g., industrial and agricultural discharges, and riverine input) played important roles in controlling HCH, DDT, PAH, and heavy metal distributions in coastal regions along the Chinese Bohai Sea. The outcomes of this study are expected to shed new light on an improved understanding of POP and heavy metal cycling and provide a scientific basis for contamination control in coastal systems.

Objective Hepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding of the mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis.Design In this study, to systematically investigate the characteristics of cancer-associated fibroblast (CAF) subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by CAF subsets, we generated an HCC atlas by compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify the specific CAF subsets in the TME that determine the efficacy of immunotherapy in HCC patients.Results Our findings highlight the pivotal role of POSTN+ CAFs as potent immune response barriers at specific tumor locations, as they hinder effective T-cell infiltration and decrease the efficacy of immunotherapy. Additionally, we elucidated the interplay between POSTN+ CAFs and SPP1+ macrophages, whereby the former recruits the latter and triggers increased SPP1 expression via the IL-6/STAT3 signaling pathway. Moreover, we demonstrated a spatial correlation between POSTN+ CAFs and SPP1+ macrophages, revealing an immunosuppressive microenvironment that limits the immunotherapy response. Notably, we found that patients with elevated expression levels of both POSTN+ CAFs and SPP1+ macrophages achieved less therapeutic benefit in an immunotherapy cohort.Conclusion Our research elucidates light on the role of a particular subset of CAFs in immunotherapy resistance, emphasizing the potential benefits of targeting specific CAF subpopulations to improve clinical responses to immunotherapy.

Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

Abstract Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field. Within the tumor microenvironment, PD-L1 expression is commonly utilized to predict response. Moreover, the characteristics of tumor-infiltrating lymphocytes are associated with the effectiveness of immunotherapy. Preclinical studies have identified stimulatory dendritic cells, conventional dendritic cells, and macrophages as potential biomarkers. The emergence of single-cell sequencing and spatial transcriptomics has provided invaluable insights into tumor heterogeneity through the lens of single-cell profiling and spatial distribution. With the widespread adoption of next-generation sequencing, certain genomic characteristics, including tumor mutational burden, copy number alterations, specific genes (TP53, CTNNB1, and GZMB), and signaling pathways (WNT/β-catenin) have been found to correlate with prognosis. Furthermore, clinical features such as tumor size, number, and metastasis status have demonstrated prognostic value. Notably, common indicators such as the Child-Pugh score and Eastern Cooperative Oncology Group score, which are used in patients with liver diseases, have shown potential. Similarly, commonly employed laboratory parameters such as baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes in alpha-fetoprotein (AFP) and abnormal prothrombin, CRAFITY score (composed of C-reactive protein and AFP), and immune adverse events have been identified as predictive biomarkers. Novel imaging techniques such as EOB-MRI and PET/CT employing innovative tracers also have potential. Moreover, liquid biopsy has gained widespread use in biomarker studies owing to its non-invasive, convenient, and highly reproducible nature, as well as its dynamic monitoring capabilities. Research on the gut microbiome, including its composition, dynamic changes, and metabolomic analysis, has gained considerable attention. Efficient biomarker discovery relies on continuous updating of treatment strategies. Next, we summarized recent advancements in clinical research on HCC immunotherapy and provided an overview of ongoing clinical trials for contributing to the understanding and improvement of HCC immunotherapy.

To address the issue of reliable communication under complicated scenarios, an online learning-assisted intelligent OFDM receiver was proposed.The variations of the channel environment could be precepted by the receiver, and the optimal parameters of the receiver under the current scenario were obtained by collecting data and training online.In the channel estimation module of the OFDM system, a performance comparator based on the mean square error of noisy channel samples was designed as the indicator of channel environment variations.To accelerate the online training progress, a lightweight neural network structure was applied.The proposed method was further implemented and verified based on universal software radio peripherals.The numerical simulation and over-the-air experimental results demonstrate that the proposed receiver can perceive and adapt to new environments effectively, and outperforms existing machine learning methods in terms of receiving performance and convergence rate with a limited number of pilots.

The intelligent communication and networking technologies for manned/unmanned cooperation was comprehensively surveyed.Firstly, the requirements on communication and networking were analyzed from the application scenarios of manned/unmanned cooperation.Then, in context of physical layer, link layer and network layer respectively, the key issues regarding channel modeling, waveform design, networking protocol and intelligent collaboration were analyzed.And the states-of-the-art in this research area and the characteristics of representative technologies were deeply studied.In the end, the possible development trends and promising technologies were prospected on the way to make the manned/unmanned cooperative communication and networking more intelligent, more efficient and more flexible.

Acicular ferrite (AF) has been regarded as the optimal microstructure in steel welds and heat affect zones (HAZs), because of its superior combination of strength and toughness. Although various aspects of AF have been investigated, the crystallographic characteristics of AF, including orientation relationship, variant selection and variant pairing, are still not fully studied. In this research, a Ti-deoxidized high strength low alloy steel was prepared and subjected to HAZ thermal cycle simulation tests to attain AF microstructure. Optical micrographs were obtained and EBSD mappings of AF microstructures were conducted. Through crystallographic analysis, the orientation relationship between AF and austenite was found close to that of bainite transformed at a high temperature (580 °C). In the AF microstructure, all 24 variants are formed and variant selection is nearly random. Compared with bainite, the variant pairing of AF is more random despite the slight favour of certain variant pairs. Most of the adjacent AF laths are from different close-packed plane (CP) groups, leading to the classic interlocking morphology. Meanwhile, a large number of neighbouring AF laths belong to different Bain groups, resulting in a high density of high angle grain boundaries (HAGBs). Intragranular nucleation of primary AF laths on inclusions contributes both to the high HAGB density and to the interlocking morphology of AF, while the sympathetic nucleation of secondary AF laths only contributes to the latter. These results suggest that to increase the HAGB density in AF, promoting the intragranular nucleation on inclusions is more important than enhancing the sympathetic nucleation.

Abstract Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P

[INLINE:1] Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer’s disease, but its effect on stroke is still poorly understood. In this study, we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes. We treated the rats with exercise and melatonin therapy for 7 consecutive days. Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats, increased delta power values, and regularized delta power rhythm. Additionally, exercise-with-melatonin therapy improved coordination, endurance, and grip strength, as well as learning and memory abilities. At the same time, it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone. These findings suggest that exercise-with-melatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.

In response to the problem of limited performance and low spectral efficiency in complex multipath environments of traditional direct sequence spread spectrum communication, a cyclic prefix (CP) block transmission structure spread spectrum system with a time-frequency hybrid direct sequence spread spectrum receiver structure was proposed.The system adopted maximum ratio combination (MRC) in the frequency domain to achieve equalization and de-spreading processes simultaneously, while achieving optimal reception performance and omitting the IFFT process to reduce computational complexity significantly.On this basis, it was proposed to replace the m-sequence with the constant amplitude zero auto correlation (CAZAC) sequence as the spread spectrum sequence, which significantly improved the system performance without increasing computational complexity.Finally, a high-speed spread spectrum communication method based on cyclic code shift keying (CCSK) was proposed to solve the problems of low spectrum utilization efficiency and limited transmission rate in traditional direct sequence spread spectrum.By utilizing the property of Fourier transform time-domain cyclic shift, a low implementation complexity CCSK decoding method was designed, which reduced the multiplication number required for CCSK de-spreading by O(N2) reduced to O (Nlog N), greatly reducing resource consume.The simulation results show that compared to existing direct sequence spread spectrum methods, the proposed method achieves approximately 3 dB gain in both Gaussian and complex multipath channel environments.

Abstract Immune checkpoint blockade (ICB) has become a promising strategy in treating advanced cancers, providing significant survival benefits for patients with various cancer types. However, among the vast population of cancer patients, only a small fraction are able to respond to and derive benefits from ICB therapy. Numerous factors contribute to the diminished efficacy of ICB, with the complex tumor microenvironment (TME) playing an important role. Therefore, comprehensively understanding the intricate composition of the TME is critical for elucidating the mechanisms that underlie distinct responses to ICB in patients. Single-cell RNA sequencing (scRNA-seq) is a novel technique that reveals gene expression profiles of individual cells, facilitating the investigation of TME heterogeneity at a high resolution and the identification of key cell subsets participating in the response to ICB. This review emphasizes the importance of scRNA-seq in studying ICB and summarizes recent findings in the discovery of biomarkers that predict ICB response and novel potential therapeutic targets for immunotherapy. These findings suggest future directions for the clinical implementation of cancer immunotherapy, facilitating further advancements in precision medicine.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality; it ranks as the second most common cause of cancer deaths in China. Most HCC patients are first diagnosed at an advanced stage. In recent years, targeted therapy combined with immunotherapy has become the preferred regimen for systemic treatment of intermediate-advanced HCC, while targeted therapy combined with immunotherapy plus local treatment could further improve the efficacy in many clinical studies. To better guide the clinical treatment for effective and safe combination therapy, our interdisciplinary panel on the treatment of intermediate-advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, interventional radiologists, and traditional Chinese medicine physicians have formulated this consensus based on current clinical studies and clinical medication experience for reference. The consensus contained 15 recommendations, including the applicable population and management, local treatment selection, conversion strategy, treatment strategy after tumor progression and management of common adverse reactions.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Adoption among nonhuman primates (hereafter primates) has been widely reported, particularly in chimpanzees, renowned for their higher intelligence and well-developed cognition. In contrast to adoption in other Old World monkeys, this case of adoption in golden snub-nosed monkeys (Rhinopithecus roxellana) involves two infants associated with three units characterized by distinct social structures and reproductive functions. Consequently, this case extends beyond traditional hypotheses on allomaternal care and adoption—such as enhancing the fitness of adoptive mothers, fostering maternal behaviors, and improving fitness through social and individual interactions—to necessitate an association with the complex social structure characterized by hierarchical, multilevel composition, akin to human society, and intense sexual selection that frequently results in infanticide. Specifically, adopting an infant with a genetic link to the dominant male of the adopting female may reduce the risk of infanticide against her offspring that do not share a biological link with the dominant male. This adoption pattern suggests that golden snub-nosed monkeys may possess more sophisticated intelligence and cognition, characteristics supported by more developed brain structure and facial muscles than the other Old World monkeys.

Directional unmanned aerial vehicle (UAV) ad hoc networks (DUANETs) are widely applied due to their high flexibility, strong anti-interference capability, and high transmission rates. However, within directional networks, complex mutual interference persists, necessitating scheduling of the time slot, power, and main lobe direction for all links to improve the transmission performance of DUANETs. To ensure transmission fairness and the total count of transmitted data packets for the DUANET under dynamic data transmission demands, a scheduling algorithm for the time slot, power, and main lobe direction based on multi-agent deep reinforcement learning (MADRL) is proposed. Specifically, modeling is performed with the links as the core, optimizing the time slot, power, and main lobe direction variables for the fairness-weighted count of transmitted data packets. A decentralized partially observable Markov decision process (Dec-POMDP) is constructed for the problem. To process the observation in Dec-POMDP, an attention mechanism-based observation processing method is proposed to extract observation features of UAVs and their neighbors within the main lobe range, enhancing algorithm performance. The proposed Dec-POMDP and MADRL algorithms enable distributed autonomous decision-making for the resource scheduling of time slots, power, and main lobe directions. Finally, the simulation and analysis are primarily focused on the performance of the proposed algorithm and existing algorithms across varying data packet generation rates, different main lobe gains, and varying main lobe widths. The simulation results show that the proposed attention mechanism-based MADRL algorithm enhances the performance of the MADRL algorithm by 22.17%. The algorithm with the main lobe direction scheduling improves performance by 67.06% compared to the algorithm without the main lobe direction scheduling.

UAV thermal infrared remote sensing technology, with its high flexibility and high temporal and spatial resolution, is crucial for understanding surface microthermal environments. Despite DJI Drones’ industry-leading position, the JPG format of their thermal images limits direct image stitching and further analysis, hindering their broad application. To address this, a format conversion system, ThermoSwitcher, was developed for DJI thermal JPG images, and this system was applied to surface microthermal environment analysis, taking two regions with various local zones in Nanjing as the research area. The results showed that ThermoSwitcher can quickly and losslessly convert thermal JPG images to the Geotiff format, which is further convenient for producing image mosaics and for local temperature extraction. The results also indicated significant heterogeneity in the study area’s temperature distribution, with high temperatures concentrated on sunlit artificial surfaces, and low temperatures corresponding to building shadows, dense vegetation, and water areas. The temperature distribution and change rates in different local zones were significantly influenced by surface cover type, material thermal properties, vegetation coverage, and building layout. Higher temperature change rates were observed in high-rise building and subway station areas, while lower rates were noted in water and vegetation-covered areas. Additionally, comparing the temperature distribution before and after image stitching revealed that the stitching process affected the temperature uniformity to some extent. The described format conversion system significantly enhances preprocessing efficiency, promoting advancements in drone remote sensing and refined surface microthermal environment research.

High-strength press-hardened steels (PHSs) are characterized by a martensite structure of high strength and adequate ductility. Strengthening PHSs with high C contents is usually accompanied by a loss of ductility and toughness. To overcome this inherent strength–ductility trade-off dilemma, we propose a novel strategy to achieve outstanding mechanical performance by introducing stable high-density Cr-rich cementite, which refines the martensite structure via Zenner pinning effect in a novel 2000 MPa grade PHS. Specifically, a high tensile strength of 2085 MPa with an appreciable total elongation of 10.1% is achieved in the novel PHS, which is far superior to commercial 22MnB5 steel (1519 MPa and 10%). The strength increase is predominantly induced by a high density of dislocations and cementite in the novel PHS, while the good ductility is attributed to the refined martensite structure coordinating plastic deformation and the enhanced work-hardening ability and dislocation storage capability mediated by massive cementite. The work can lay foundations for designing high-strength PHSs with good ductility.

Background The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors immunotherapy landscape.Methods By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC).Results While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies.Conclusions We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments.Trial registration number NCT06165874.

Aiming at the problem that most current researches on text semantic communication mainly rely on simulation system for theoretical verification, an extensible hierarchical semantic communication system was proposed by taking advantage of the separation of hierarchical encoding and decoding architecture in semantic level and grammatical level.The system was compatible with the reliable communication technology under the framework of Shannon information through the mode of semantic and syntactic separation, and realized the nested combination of semantic communication and traditional communication.Furthermore, a universal and extensible verification system was built based on the software radio platform to verify the proposed semantic communication system architecture.The verification system took semantic communication software platform as the driving core of hardware drive and algorithm call, integrated the whole process of signal generation, information transmission, data acquisition, decoding and evaluation at the receiving end, and could be further extended for semantic and syntactic level.Finally, the text semantic communication was tested based on this verification system, which verified that it had higher validity and reliability than the traditional communication mode.

A communication system based on extended contextual semantic features was proposed by using an end-to-end integrated design method based on deep learning.Unlike existing research that focused only on local context while neglecting global context, the proposed system integrated both local and global contextual knowledge, semantic encoding and decoding was utilized by extended contextual knowledge, thereby enhancing the reliability of the semantic communication system.At the transmitter, efficient semantic representation was achieved through extended contextual semantic encoding.At the receiver, the accuracy of semantic inference was improved by combining mechanisms such as historical communication text mining, contextual semantic feature learning, and heuristic graph-based decoding strategy.When comparing with the traditional communication system and the existing semantic communication systems, simulation results demonstrate that the proposed system significantly improves the reliability of the communication system under low signal-to-noise ratio.

Abstract Background Early screening and detection of hepatocellular carcinoma (HCC) can efficiently improve patient prognosis. We aimed to identify a series of hypermethylated DNA markers and develop a blood-based HCC diagnosis panel containing DNA methylation sites and protein markers with improved sensitivity for early-stage HCC detection. Results Overall, 850K methylation arrays were performed using paired tissue DNA samples from 60 HCC patients. Ten candidate hypermethylated CpG sites were selected for further evaluation by quantitative methylation-specific PCR with 60 pairs of tissue samples. Six methylated CpG sites, along with α-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP), were assayed in 150 plasma samples. Finally, an HCC diagnosis panel, named HepaClear, was developed in a cohort consisting of 296 plasma samples and validated in an independent cohort consisting of 198 plasma samples. The HepaClear panel, containing 3 hypermethylated CpG sites (cg14263942, cg12701184, and cg14570307) and 2 protein markers (AFP and DCP), yielded a sensitivity of 82.6% and a specificity of 96.2% in the training set and a sensitivity of 84.7% and a specificity of 92.0% in the validation set. The HepaClear panel had higher sensitivity (72.0%) for early-stage HCC than AFP (≥ 20 ng/mL, 48.0%) and DCP (≥ 40 mAU/mL, 62.0%) and detected 67.5% of AFP-negative HCC patients (AFP ≤ 20 ng/mL). Conclusions We developed a multimarker HCC detection panel (HepaClear) that shows high sensitivity for early-stage HCC. The HepaClear panel exhibits high potential for HCC screening and diagnosis from an at-risk population.