Facilitating Charge Transfer via Ti-Knot Pathway in Electrochromic Three-Dimensional Metalated Covalent Organic Frameworks.

Due to the ordered one-dimensional channel as well as accessible redox sites, two-dimensional covalent organic frameworks (2D COFs) have garnered extensive attention in the field of electrochromism. However, organic 2D frameworks impose limitations on charge transfer and the weak interlayer interactions in 2D COFs, adversely affecting the stability during switching processes. Herein, we introduced Ti knots to construct three-dimensional metalated covalent organic frameworks (3D MCOFs), denoted as Ti-DHTA-Py. The Ti knots not only serve as templates for organizing organic units into unique 3D topological structures in a controlled manner but also establish charge transfer pathways conducive to electron delocalization and transmission within the framework. As a result, the 3D Ti-DHTA-Py MCOFs electrode exhibited a reduced band gap and remarkable electrochromic (EC) performances: electrochemical cyclic stability of 93.6% retention after 500 cycles, switching times (2.5 s/0.5 s), and a high coloration efficiency (423 cm2 C-1). This research underscores the potential of 3D MCOFs as promising candidates for advancing EC technologies, surmounting the limitations associated with traditional 2D COFs.

A bioabsorbable mechanoelectric fiber as electrical stimulation suture.

In surgical medicine, suturing is the standard treatment for large incisions, yet traditional sutures are limited in functionality. Electrical stimulation is a non-pharmacological therapy that promotes wound healing. In this context, we designed a passive and biodegradable mechanoelectric suture. The suture consists of multi-layer coaxial structure composed of (poly(lactic-co-glycolic acid), polycaprolactone) and magnesium to allow safe degradation. In addition to the excellent mechanical properties, the mechanoelectrical nature of the suture grants the generation of electric fields in response to movement and stretching. This is shown to speed up wound healing by 50% and reduce the risk of infection. This work presents an evolution of the conventional wound closure procedures, using a safe and degradable device ready to be translated into clinical practice.

A selective frequency damping and Janus adhesive hydrogel as bioelectronic interfaces for clinical trials.

Maintaining stillness is essential for accurate bioelectrical signal acquisition, but dynamic noise from breathing remains unavoidable. Isotropic adhesives are often used as bioelectronic interfaces to ensure signal fidelity, but they can leave irreversible residues, compromising device accuracy. We propose a hydrogel with selective frequency damping and asymmetric adhesion as a bioelectronic interface. This hydrogel mitigates dynamic noise from breathing, with a damping effect in the breathing frequency range 60 times greater than at other frequencies. It also exhibits an asymmetric adhesion difference of up to 537 times, preventing residues. By homogenizing ion distribution, extending Debye length, and densifying the electric field, the hydrogel ensures stable signal transmission over 10,000 cycles. Additionally, it can non-invasively diagnose otitis media with higher sensitivity than invasive probes and has been effective in clinical polysomnography monitoring, aiding in the diagnosis of obstructive sleep apnea.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis.

PURPOSE: This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN). MATERIALS AND METHODS: Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). CONCLUSIONS: Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05).

PURPOSE: This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. METHODS: Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups. RESULTS: In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively. CONCLUSION: The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.

Air-Processed Efficient Perovskite Solar Cells With Full Lifecycle Management.

Despite the outstanding power conversion efficiency of perovskite solar cells (PSCs) realized over the years, the entire lifecycle from preparation and operation to discarding of PSCs still needs to be carefully considered when it faces the upcoming large-scale production and deployment. In this study, bio-derived chitin-based polymers are employed to realize the full lifecycle regulation of air-processed PSCs by forming multiple coordinated and hydrogen bonds to stabilize the lead iodide and organic salt precursor inks, accelerating the solid-liquid reaction and crystallization of two-step deposition process, then achieving the high crystalline and oriented perovskites with less notorious charge defects in the open air. The air-prepared PSCs exhibit a decent efficiency of 25.18% with high preparation reproducibility and improved operational stability toward the harsh environment and mechanical stress stimuli. The modified PSCs display negligible fatigue behavior with keeping 92% of its initial efficiency after operating for 32 diurnal cycles (ISOS-LC-1 protocol). Meanwhile, closed-loop lead management of end-of-life PSCs including suppression of lead leakage, toxicity evaluation of broken devices, and recycling of lead iodide components are comprehensively investigated. This work sheds light on a promising avenue to realize the entire lifecycle regulation of air-processed efficient and stable PSCs.

Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa. RECENT FINDINGS: Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines. CONCLUSION: The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

A novel approach to quantitate biodistribution and transduction of adeno-associated virus gene therapy using radiolabeled AAV vectors in mice.

An understanding of recombinant adeno-associated virus (AAV) biodistribution profiles is an important element of a preclinical development program. Here, we have developed a radiolabeling strategy utilizing the co-delivery of 125I (non-residualizing) and 111In (residualizing) radionuclide-conjugated AAVs to provide a detailed distribution quantification at tissue level delineating between the cellular internalized AAV (degraded, 111In-125I) and AAV remaining in the extracellular matrix (intact, 125I). This labeling method has been successfully applied to AAV9 and AAV-PHP.eB as tool molecules without altering the physical properties and biological activities of the AAVs. Upon labeling with either of the radioactive probes, these molecules were systemically injected into C57BL/6 mice. The biodistribution results indicate that AAVs, with a fast distribution profile, were mainly located in the extracellular matrix of highly perfused organs such as liver and spleen at early time points, leading to a difference between capsid quantification and vector genome quantification. The results suggest that the 125I-AAV/111In-AAV co-delivery approach offers a robust and efficient analytical strategy to investigate the detailed tissue distribution of AAV vectors, including both vector genome and protein capsids. This novel method has the potential to be applied to capsid optimization, selection, and lead candidate development.

Ultralong Bistable, Electrolytic MnO2-Based, Electrochromic Battery Enabled by Porous, Low-Barrier, Hydroxylated TiO2 Interface.

Electrochromic (EC) battery technology shows great potential in future "zero-energy building" by controlling outdoor solar transmission to tune heat gain as well as storing the consumed energy to reuse across other building systems. However, challenges still exist in exploring an electrochemical system to satisfy requirements on both ultra-long optical memory (also called bistability) without continuous power supply and high energy density. Herein, an EC battery is proposed to demonstrate ultra-long bistability (>760 h) based on the reversible deposition and dissolution of manganese oxide (MnO2) without the addition of any mediators. A porous low-barrier hydroxylated titanium dioxide (TiO2) interface is incorporated to synergistically enrich Mn2+-affinity active sites for deposition and effectively reduce the electron transport barrier of MnO2 for dissolution, thereby significantly improving the reversibility, high optical modulation (60.2% at 400 nm), and energy density (352 mAh m-2). The modification strategy is also verified on the cathode-less button cells with a much higher average coulombic efficiency (99.9%) compared to the batteries without the porous hydroxylated TiO2 interface (74.6%). These achievements lay a foundation for advancements in both electrochromism and Zn-Mn aqueous batteries.

Simultaneous noninvasive ultrasensitive detection of prostate specific antigen and lncRNA PCA3 using multiplexed dual optical microfibers with strong plasmonic nanointerfaces.

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10-15 mol/L and 1.56 × 10-14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

Diagnosis and treatment of refractory infectious diseases using nanopore sequencing technology: Three case reports.

BACKGROUND: Infectious diseases are still one of the greatest threats to human health, and the etiology of 20% of cases of clinical fever is unknown; therefore, rapid identification of pathogens is highly important. Traditional culture methods are only able to detect a limited number of pathogens and are time-consuming; serologic detection has window periods, false-positive and false-negative problems; and nucleic acid molecular detection methods can detect several known pathogens only once. Three-generation nanopore sequencing technology provides new options for identifying pathogens. CASE SUMMARY: Case 1: The patient was admitted to the hospital with abdominal pain for three days and cessation of defecation for five days, accompanied by cough and sputum. Nanopore sequencing of the drainage fluid revealed the presence of oral-like bacteria, leading to a clinical diagnosis of bronchopleural fistula. Cefoperazone sodium sulbactam treatment was effective. Case 2: The patient was admitted to the hospital with fever and headache, and CT revealed lung inflammation. Antibiotic treatment for Streptococcus pneumoniae, identified through nanopore sequencing of cerebrospinal fluid, was effective. Case 3: The patient was admitted to our hospital with intermittent fever and an enlarged neck mass that had persisted for more than six months. Despite antibacterial treatment, her symptoms worsened. The nanopore sequencing results indicate that voriconazole treatment is effective for Aspergillus brookii. The patient was diagnosed with mixed cell type classical Hodgkin's lymphoma with infection. CONCLUSION: Three-generation nanopore sequencing technology allows for rapid and accurate detection of pathogens in human infectious diseases.

An afferent nerve-like electronic device with somatic mechanical perception and sensation management.

Tactile and pain perception are essential for biological skin to interact with the external environment. This complex interplay of sensations allows for the detection of potential threats and appropriate responses to stimuli. However, the challenge is to enable flexible electronics to respond to mechanical stimuli such as biological skin, and researchers have not clearly reported the successful integration of somatic mechanical perception and sensation management functions into neuro-like electronics. In this work, an afferent nerve-like device with a pressure sensor and a perception management module is proposed. The pressure sensor comprises two conductive fabric layers and an ionic hydrogel, forming a capacitor structure that emulates the swift transition from tactile to pain perception under mechanical stimulation. Drawing inspiration from the neuronal "gate control" mechanism, the sensation management module adjusts signals in response to rubbing, accelerating the discharge process and reducing the perception duration, thereby replicating the inhibitory effect of biological neurons on pain following tactile interference. This integrated device, encompassing somatic mechanical perception and sensation management, holds promise for applications in soft robotics, prosthetics, and human-machine interaction.

Scale-Bridging Mechanics Transfer Enables Ultrabright Mechanoluminescent Fiber Electronics.

Mechanoluminescent (ML) fibers and textiles enable stress visualization without auxiliary power, showing great potential in wearable electronics, machine vision, and human-computer interaction. However, traditional ML devices suffer from inefficient stress transfer in soft-rigid material systems, leading to low luminescence brightness and short cycle life. Here, we propose a tendon-inspired scale-bridging mechanics transfer mechanism for ML composites, which employs molecular-scale copolymerized cross-linking and nanoscale inorganic nanoparticles as hierarchical stress transfer sites. This strategy effectively reduces the dissipation of stress in molecular chain segments and alleviates local stress concentration, increases luminescence by 9 times, and extends cycle life to more than 10,000 times. Furthermore, a scalable (kilometer-scale) anti-Plateau-Rayleigh instability manufacturing technology is developed for thermoset ML fibers, compatible with various existing textile techniques. We also demonstrate its system-level applications in motion capture, underwater interaction, etc., providing a feasible strategy for the next generation of smart visual textiles.

Working Memory Guides Action Valuation in Model-based Decision-making Strategy.

Humans use both model-free (or habitual) and model-based (or goal-directed) strategies in sequential decision-making. Working memory (WM) is essential for the model-based strategy; however, its exact role in these processes remains elusive. This study investigates the influence of WM processes on decision-making and the underlying cognitive computing mechanisms. Specifically, we used experimental data from two-stage decision tasks and found that delay and load, two WM-specific variables, impact goal-revisiting behaviors. Then, we proposed possible computational mechanisms by which WM participates in information processing and integrated them into the model-based system. The proposed Hybrid-WM model reproduced the observed experimental effects and fit human behavior better than the classic hybrid reinforcement learning model. These results were verified with independent data sets. Furthermore, differences in model parameters explain the age-related difference in sequential decision-making. Overall, this study suggests that WM guides action valuation in model-based strategies, highlighting the contribution of higher cognitive functions to sequential decision-making.

Energy-Efficient, Cluster-Based Routing Protocol for Wireless Sensor Networks Using Fuzzy Logic and Quantum Annealing Algorithm.

The main limitation of wireless sensor networks (WSNs) lies in their reliance on battery power. Therefore, the primary focus of the current research is to determine how to transmit data in a rational and efficient way while simultaneously extending the network's lifespan. In this paper, a hybrid of a fuzzy logic system and a quantum annealing algorithm-based clustering and routing protocol (FQA) is proposed to improve the stability of the network and minimize energy consumption. The protocol uses a fuzzy inference system (FIS) to select appropriate cluster heads (CHs). In the routing phase, we used the quantum annealing algorithm to select the optimal route from the CHs and the base station (BS). Furthermore, we defined an energy threshold to filter candidate CHs in order to save computation time. Unlike with periodic clustering, we adopted an on-demand re-clustering mechanism to perform global maintenance of the network, thereby effectively reducing the computation and overhead. The FQA was compared with FRNSEER, BOA-ACO, OAFS-IMFO, and FC-RBAT in different scenarios from the perspective of energy consumption, alive nodes, network lifetime, and throughput. According to the simulation results, the FQA outperformed all the other methods in all scenarios.

Evaluating the effect of health insurance reform on health equity and financial protection for elderly in low- and middle-income countries: evidences from China.

BACKGROUND: To achieve Universal Health Coverage (UHC), China have implemented health system reform to expend health coverage and improve health equity. Scholars have explored the implementing effect of this health reform, but gaps remained in health care received by elderly. This study aims to assess the effect of implementing health insurance payment reform on health care received by elderly, as well as to evaluate its effect on cost sharing to identify whether improve financial protection of elderly under this reform. METHODS: We identified hospitalization of 46,714 elderly with cerebral infarction from 2013 to 2023. To examine the determinant role played by DRGs payment reform in healthcare for elderly and their financial protection, this study employs the OLS linear regression model for analysis. In the robustness checks, we validated the baseline results through several methods, including excluding the data from the initial implementation of the reform (2021), reducing the impact of the pandemic, and exploring the group effects of different demographic characteristics. RESULTS: The findings proposed that implementing DRGs payment reduces drug expenses but increases treatment expense of chronic disease for elderly in China. This exacerbates healthcare costs for elderly patients and seems to be contrary to the original purpose of health care reform. Additionally, the implementation of DRGs payment reduced the spending of medical insurance fund, while increased the out-of-pocket of patients, revealing a shift in health care expenses from health insurance fund to out-of-pocket. CONCLUSIONS: This study shares the lessons from China's health reform and provides enlightenment on how to effective implement health reform to improve health equity and achieve UHC in such low- and middle-income countries facing challenges in health financing.