Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

Seeking Cells, Targeting Bacteria: A Cascade-Targeting Bacteria-Responsive Nanosystem for Combating Intracellular Bacterial Infections.

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.

Baseline serum testosterone and differential efficacy of bipolar androgen therapy and enzalutamide in the randomized TRANSFORMER trial.

Bipolar androgen therapy (BAT) is effective in a subset of metastatic castration-resistant prostate cancer (mCRPC) patients. Treatment selection biomarkers are needed due to other therapies that can be equally efficacious. We performed post-hoc analysis to determine whether baseline serum testosterone (T) is a treatment selection marker in the TRANSFORMER study, a randomized trial of abiraterone-pretreated mCRPC patients assigned to BAT (n = 94) or enzalutamide (n = 101). The findings suggest that patients with poor outcomes to abiraterone and serum T ≥ 20 ng/dL may benefit preferentially from BAT over enzalutamide. Baseline testosterone could be considered in the treatment selection process when BAT is an option.

Gradient Dopzing enables an Extraordinary Efficiency in Thermoelectric PbTe1- xIx.

The conversion efficiency of thermoelectric generators that have to be operated under a temperature difference (ΔT), is mainly determined by material's dimensionless figure of merit (zT). However, maximization of zT at each temperature requires an optimization of carrier concentration (nopt) which strongly depends on the temperature and band parameters. Commonly utilized strategy of chemical doping usually enables a homogeneous carrier concentration throughout the material, leading the maximal zT to be achievable only within a narrow temperature range. In this work, a gradiently doping is successfully realized in PbTe1- xIx using a vertical gradient solidification technique, enabling a spatial gradient in carrier concentration that correspondingly optimizes zT at each portion of the material under its operating temperature. Such a gradient doping results in an extraordinary device efficiency of ∼14% at a ΔT of ∼500 K, corresponding to a ∼40% improvement as compared to that of homogeneous doping. Since directional solidification technique commonly enables gradient dopant concentrations in semiconductors, the resultant gradient carrier concentration is illustrated here as an effective approach for advancing thermoelectrics. This article is protected by copyright. All rights reserved.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Formation, stability, and antimicrobial efficacy of eutectic nanoemulsions containing thymol and glycerin monolaurate.

In this study, based on the discovery of thymol/glycerol monolaurate (GML) eutectic solvent, we studied the effect of GML as a multi-functional component (ripening inhibitor and antibacterial agent) on the formation, stability and antibacterial activity of eutectic nanoemulsions, and investigated the preservation of nanoemulsion in fresh pork. These results indicated that the formation of eutectic solvent was due to the hydrogen bonding between thymol and GML in the molten state. And eutectic nanoemulsions prepared with medium GML concentrations (20%, 40%, and 60%) of eutectic solvents as oil phases had small droplet diameters (<150 nm), exhibited sustained-release characteristics, and had excellent physicochemical stability. Moreover, the addition of GML enhanced the antibacterial activity of thymol nanoemulsion against S. aureus. as seen by their ability to inhibit affect formation more effectively. Treatment of fresh pork with optimized eutectic nanoemulsions (40% thymol/60% GML) extended its shelf life during refrigeration, which was mainly attributed to the ability of the encapsulated essential oil to inhibit microbial growth and lipid oxidation. These results provide a novel strategy to control Ostwald ripening and maintain the high antibacterial activity of thymol in nanoemulsion-based delivery systems.

Widely Targeted Metabolomic Analysis Revealed the Diversity in Milk from Goats, Sheep, Cows, and Buffaloes and Its Association with Flavor Profiles.

The milk flavor can be attributed to the presence of numerous flavor molecules and precursors. In this study, we employed widely targeted metabolomic analysis techniques to analyze the metabolic profiles of various milk samples obtained from goats, sheep, dairy cows, and buffaloes. A total of 631 metabolites were identified in the milk samples, which were further categorized into 16 distinct classes. Principal component analysis (PCA) suggested that the metabolite profiles of samples from the same species exhibit clustering, while separated patterns of metabolite profiles are observed across goat, sheep, cow, and buffalo species. The differential metabolites between the groups of each species were screened based on fold change and variable importance in projection (VIP) values. Five core differential metabolites were subsequently identified, including 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid, inosine 5'-triphosphate, methylcysteine, N-cinnamylglycine, and small peptide (L-tyrosine-L-aspartate). Through multiple comparisons, we also screened biomarkers of each type of milk. Our metabolomic data showed significant inter-species differences in the composition and concentration of some compounds, such as organic acids, amino acids, sugars, nucleotides, and their derivatives, which may affect the overall flavor properties of the milk sample. These findings provided insights into the molecular basis underlying inter-species variations in milk flavor.

A programmable topological photonic chip.

Controlling topological phases of light allows the observation of abundant topological phenomena and the development of robust photonic devices. The prospect of more sophisticated control with topological photonic devices for practical implementations requires high-level programmability. Here we demonstrate a fully programmable topological photonic chip with large-scale integration of silicon photonic nanocircuits and microresonators. Photonic artificial atoms and their interactions in our compound system can be individually addressed and controlled, allowing the arbitrary adjustment of structural parameters and geometrical configurations for the observation of dynamic topological phase transitions and diverse photonic topological insulators. Individual programming of artificial atoms on the generic chip enables the comprehensive statistical characterization of topological robustness against relatively weak disorders, and counterintuitive topological Anderson phase transitions induced by strong disorders. This generic topological photonic chip can be rapidly reprogrammed to implement multifunctionalities, providing a flexible and versatile platform for applications across fundamental science and topological technologies.

A Cascaded Multimodule Image Enhancement Framework for Underwater Visual Perception.

Underwater images usually exhibit severe color cast, hazy appearance, and/or dark regions because of the complex lighting absorption and scattering in water. How to increase the quality of these degraded underwater images has emerged as a key issue for various underwater application tasks. Recent efforts have been made to deal with single type degradation, however, it is still challenging to deal with multiple degradations that usually coexist in an underwater image with a general network. The degradations in underwater images can be divided into medium-agnostic (hazy or low-light which also encountered in in-air images) and medium-specific (color distortion caused by the specific light attenuation property in water) ones. According to this observation, this article proposes a cascaded multimodule underwater image enhancement (UIE) framework to address the coexisted multiple degradations. In the proposed framework, an in-air image enhancement module and a novel proposed adaptive color channel compensation network (AC 3 Net) are cascaded, in which the former focuses primarily on solving medium-agnostic degradations and the latter is for handling the medium-specific degradation. This framework has good flexibility by cascading different types of in-air image enhancement networks with AC 3 Net to achieve various UIE. The effectiveness of the proposed framework has been extensively validated on various degraded underwater images as well as different underwater visual perception tasks.

A novel anti-loosening bolt looseness diagnosis of bolt connections using a vision-based technique.

Bolt looseness detection is a common problem in engineering. Most vision-based detection techniques focus on diagnosing ordinary bolt looseness, i.e., the methods used for diagnosis are based only on the sidelines of nuts. These methods cannot be used for anti-loosening bolt looseness diagnosis because of the simultaneous rotation of screws and nuts. Therefore, a novel anti-loosening bolt looseness diagnosis method based on a vision-based technique is proposed in this paper. First, a regular hexagonal cap was installed on the screw, which can be used as a reference for the nut. Then, to automatically distinguish the hexagonal borders of the screw cap and nut, a new hexagonal border reconstruction algorithm is proposed. Furthermore, the relative rotation angles of the screw cap and nut hexagons can be determined using the sidelines of the reconstructed hexagonal borders of the screw cap and nut. Finally, a novel anti-loosening bolt looseness diagnosis method is established by using the relative rotation angle of the regular hexagonal borders of the screw cap and nut under initial status and loose status. A prototype flange node of the transmission tower was used for experimental verification. The results show that the proposed method can effectively detect the loosening angle of anti-loosening bolts.

Synergy of lytic phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii.

Phage-antibiotic combination treatment is a novel noteworthy drug delivery method in anti-infection. In the current study, we have isolated a new phage, pB23, against carbapenem-resistant Acinetobacter baumannii 2023. Synergistic antibacterial effect between phage pB23 and meropenem combination could be more stable, using moderate doses of phage (multiplicity of infection ranging from 0.1 to 1,000) based on results of in vitro antibacterial activity. Phage pB23 and meropenem combination could effectively clear mature biofilms and prevent biofilm formation of carbapenem-resistant Acinetobacter baumannii in vitro. Phage pB23 and meropenem combination also has good synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii in different growth phases under static culture conditions. The pig skin explant model shows that phage pB23 and meropenem combination has a synergistic effect to remove bacteria from wounds ex vivo. Phage pB23 and meropenem combination also exhibited a synergistic antibacterial effect in vivo using a zebrafish infection mode. The potential promotion of phage proliferation by meropenem and the sensitivity recovery of phage-resistant bacteria to meropenem might elucidate the mechanism of the synergistic antimicrobial activity. In summary, our study illustrates that phage pB23 and meropenem combination could produce synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii under static growth conditions. This study also demonstrates that phage-antibiotic combination will become an effective strategy to enhance antibacterial activity of individual drug and provide a new idea of the drug development for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii and other multidrug-resistant bacteria.

Distal margin distance in radical resection of locally advanced rectal cancer after neoadjuvant therapy.

Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse. Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function. However, there is currently no consensus on the specific distance of distal resection margin.

Anti-inflammatory lindenane sesquiterpenoid dimers from the roots of Chloranthus holostegius var. trichoneurus.

Two new lindenane-type sesquiterpenoid dimers, chlotrichenes C and D (1 and 2) together with five known lindenane-type sesquiterpenoid dimers (3-7) were isolated from the roots of Chloranthus holostegius var. trichoneurus, a famous natural medicine named as "Sikuaiwa" for subduing swellings and relieving pain. The structures including absolute configuration were elucidated by their 1D and 2D NMR, HRESIMS, and ECD data. Compounds 1 and 2 were classical [4 + 2] lindenane-type sesquiterpenoid dimers that differed from known analogs in oxidation profile, side chain profile, and double bond position. The new isolates and compound 3 exhibited significant inhibitory activity on IL-1ß production (IC50: 1-15 µM) in LPS-induced THP-1 cells and other compounds exhibited inhibitory activity on NO production in LPS-induced RAW 264.7 cells (IC50: 24-33 µM).

TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism.

Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.

Easily constructed porous silver films for efficient catalytic CO2 reduction and Zn-CO2 batteries.

For the electroreduction of carbon dioxide into high value-added chemicals, highly active and selective catalysts are crucial, and metallic silver is one of the most intriguing candidate materials available at a reasonable cost. Herein, through a novel two-step operation of Ag paste/SBA-15 coating and HF etching, porous silver films on a commercial carbon paper with a waterproofer (p-Ag/CP) could be easily fabricated on a large scale as highly efficient carbon dioxide reduction reaction (CO2RR) electrocatalysts with a CO Faraday efficiency (FECO) as high as 96.7% at -1.0 V vs. the reversible hydrogen electrode (RHE), and it still reaches up to 90% FECO over applied potentials ranging from -0.8 to -1.1 V vs. the RHE. Meanwhile, the membrane electrode assembly (MEA) utilizing the p-Ag/CP catalyst has achieved a current density, FECO, and stability of ∼60 mA cm-2, >91%, and 11 h, respectively. Furthermore, the assembled aqueous Zn-CO2 battery using p-Ag/CP cathode yielded a peak power density of 0.34 mW cm-2, 75 charge-discharge cycles for 25 h, and 64% FECO at 2.5 mA cm-2. Compared with flat Ag/CP, the significant enhancement in the CO2RR activity of p-Ag/CP was mainly attributed to the distinctive porous structure and an improved three-phase boundary, which is capable of inducing the stabilization of *COOH intermediates, increased active specific surface areas, fast electron transfer kinetic and mass transportation. Further, theoretical calculations revealed that p-Ag/CP possessed an optimized energy barrier for *COOH intermediates.

A reconfigurable integrated smart device for real-time monitoring and synergistic treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a global autoimmune disease that requires long-term management. Ambulatory monitoring and treatment of RA favors remission and rehabilitation. Here, we developed a wearable reconfigurable integrated smart device (ISD) for real-time inflammatory monitoring and synergistic therapy of RA. The device establishes an electrical-coupling and substance delivery interfaces with the skin through template-free conductive polymer microneedles that exhibit high capacitance, low impedance, and appropriate mechanical properties. The reconfigurable electronics drive the microneedle-skin interfaces to monitor tissue impedance and on-demand drug delivery. Studies in vitro demonstrated the anti-inflammatory effect of electrical stimulation on macrophages and revealed the molecular mechanism. In a rodent model, impedance sensing was validated to hint inflammation condition and facilitate diagnosis through machine learning model. The outcome of subsequent synergistic therapy showed notable relief of symptoms, elimination of synovial inflammation, and avoidance of bone destruction.

Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance.

Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive (ER+) breast cancer. However, the efficacy of agents such as tamoxifen (Tam) is often compromised by the development of resistance. Here we report that cytokines-activated nuclear IKKα confers Tam resistance to ER+ breast cancer by inducing the expression of FAT10, and that the expression of FAT10 and nuclear IKKα in primary ER+ human breast cancer was correlated with lymphotoxin ß (LTB) expression and significantly associated with relapse and metastasis in patients treated with adjuvant mono-Tam. IKKα activation or enforced FAT10 expression promotes Tam-resistance while loss of IKKα or FAT10 augments Tam sensitivity. The induction of FAT10 by IKKα is mediated by the transcription factor Pax5, and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKα attenuates p53-directed repression of FAT10. Thus, our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER+ breast cancer.

Integrative Single Cell Atlas Revealed Intratumoral Heterogeneity Generation from an Adaptive Epigenetic Cell State in Human Bladder Urothelial Carcinoma.

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1-positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low-grade noninvasive and high-grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial-to-mesenchymal transition generated TPCS. TPCS has stem-cell-like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell-like epigenomic landscape, which might generate ITH without additional genetic diversification.

Coexistence of pulmonary arterial hypertension and straight back syndrome in a patient with a novel BMPR2 variant affecting cytoplasmic tail domain.

BACKGROUND: Pathologic variants in the bone morphogenetic protein receptor-2 (BMPR2) gene cause a pulmonary arterial hypertension phenotype in an autosomal-dominant pattern with incomplete penetrance. Straight back syndrome is one of the causes of pseudo-heart diseases. To date, no cases of idiopathic or heritable pulmonary arterial hypertension with straight back syndrome have been reported. CASE PRESENTATION: A 30-year-old female was diagnosed with pulmonary arterial hypertension by right heart catheterization. Computed tomography revealed a decreased anteroposterior thoracic space with heart compression, indicating a straight back syndrome. Genetic analysis by whole exome sequencing identified a novel c.2423_2424delGT (p.G808Gfs*4) germline frameshift variant within BMPR2 affecting the cytoplasmic tail domain. CONCLUSIONS: This is the first report of different straight back characteristics in heritable pulmonary arterial hypertension with a novel germline BMPR2 variant. This finding may provide a new perspective on the variable penetrance of the pulmonary arterial hypertension phenotype.