DeepSub: Utilizing Deep Learning for Predicting the Number of Subunits in Homo-Oligomeric Protein Complexes.

The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.

A Luminescent Hybrid Bimetallic Halide Family with Solvent-Coordinated Rare Earth and Alkaline Earth Metals.

Hybrid metal halides are an extraordinary class of optoelectronic materials with extensive applications. To further diversify and study the in-depth structure-property relations, we report here a new family of 21 zero-dimensional hybrid bimetallic chlorides with the general formula A(L)n[BClm] (A = rare earth (RE), alkaline earth metals and Mn; L = solvent ligand; and B = Sb, Bi and Te).  The Ln(DMSO)8[BCl6] (Ln = La, Ce, Sm, Eu, Tb, and Dy; DMSO = dimethyl sulfoxide) series shows broadband emission attributed to triplet radiative recombination from Sb and Bi, incorporating the characteristic emission of RE metals, where Eu(DMSO)8[BiCl6] shows a staggering PL quantum yield of 94%. The pseudo-octahedral [SbCl5] with Cl vacancy in AII(DMSO)6[SbCl5] (AII = Mg, Ca and Mn) and the square pyramidal [SbCl5] in AII(TMSO)6[SbCl5] (TMSO = tetramethylene sulfoxide) enhance the stereoactive expression of the 5s2 lone pairs of Sb3+, giving rise to the observation of dual-band emission of singlet and triplet emission, respectively. A series of Te(IV) analogues have been characterized, showing blue-light-excitable single-band emission. This work expands the materials space for hybrid bimetallic halides with an emphasis on harnessing the RE elements and provides important insights into designing new emitters and regulating their properties.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Innovative Bio-based Hydrogel Microspheres Micro-Cage for Neutrophil Extracellular Traps Scavenging in Diabetic Wound Healing.

Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half-life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio-based hydrogel microspheres 'micro-cage', termed mPDA-PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)-functionalized mesoporous polydopamine (mPDA). This unique 'micro-cage' construct is designed to non-contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into 'micro-cage' along with wound exudation, and cationic mPDA-PEI immobilizes them inside the 'micro-cage' through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA-PEI@GelMA effectively mitigates pro-inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non-contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

Preparation of Cobalt-Nitrogen Co-Doped Carbon Nanotubes for Activated Peroxymonosulfate Degradation of Carbamazepine.

Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.

Short-term efficacy and safety of neoadjuvant pyrotinib plus taxanes for early HER2-positive breast cancer: a single-arm exploratory phase II trial.

Background: The effectiveness and safety of pyrotinib have been substantiated in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (BC). However, the role of pyrotinib as a single HER2 blockade in neoadjuvant setting among BC patients has not been studied. The objective of this study was to evaluate the efficacy and tolerability of pyrotinib plus taxanes as a novel neoadjuvant regimen in patients with HER2-positive early or locally advanced BC. Methods: In this single-arm exploratory phase II trial, patients with treatment-naïve HER2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily and taxanes [docetaxel 75 mg/m2 or nanoparticle albumin-bound (nab)-paclitaxel 260 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly] for a total of four 21-day cycles before surgery. Efficacy assessment was based on pathological and clinical measurements. The primary endpoint of this study was the total pathological complete response (tpCR) rate. The secondary endpoints included breast pCR (bpCR) rate, investigator-assessed objective response rate (ORR) and adverse events (AEs) profiles. Results: From 1 September 2021 to 30 December 2022, a total of 31 patients were enrolled. One patient was withdrawn due to unbearable skin rash after the second cycle of neoadjuvant therapy. The majority of the intention-to-treat (ITT) population was premenopausal (54.8%), had large tumors (90.3%) and metastatic nodes (58.1%) at diagnosis and hormone-receptor positive tumors (64.5%). Most participants used nab-paclitaxel (74.2%) and received mastectomy (67.7%) after neoadjuvant treatment. The tpCR and bpCR rates were 48.4% [95% confidence interval (CI): 30.8-66%] and 51.6% (95% CI: 34-69.2%), respectively. Grade ≥3 treatment-related AEs were observed in 16.1% (5/31) of the ITT population, including diarrhea (n=2, 6.5%), hand and foot numbness (n=1, 3.2%), loss of appetite (n=1, 3.2%), and skin rash (n=1, 3.2%). AE related dose reduction or pyrotinib interruption was not required. Conclusions: In female patients with HER2-positive non-metastatic BC, neoadjuvant pyrotinib monotherapy plus taxanes appears to show promising clinical benefit and controllable AEs [Chinese Clinical Trial Registry (ChiCTR2100050870)]. The long-term efficacy and safety of this regime warrant further verification.

Transpiration-Inspired Fabric Dressing for Acceleration Healing of Wound Infected with Biofilm.

In chronic wound management, efficacious handling of exudate and bacterial infections stands as a paramount challenge. Here a novel biomimetic fabric, inspired by the natural transpiration mechanisms in plants, is introduced. Uniquely, the fabric combines a commercial polyethylene terephthalate (PET) fabric with asymmetrically grown 1D rutile titanium dioxide (TiO2) micro/nanostructures, emulating critical plant features: hierarchically porous networks and hydrophilic water conduction channels. This structure endows the fabric with exceptional antigravity wicking-evaporation performance, evidenced by a 780% one-way transport capability and a 0.75 g h-1 water evaporation rate, which significantly surpasses that of conventional moisture-wicking textiles. Moreover, the incorporated 1D rutile TiO2 micro/nanostructures present solar-light induced antibacterial activity, crucial for disrupting and eradicating wound biofilms. The biomimetic transpiration fabric is employed to drain exudate and eradicate biofilms in Staphylococcus aureus (S. aureus)-infected wounds, demonstrating a much faster infection eradication capability compared to clinically common ciprofloxacin irrigation. These findings illuminate the path for developing high-performance, textile-based wound dressings, offering efficient clinical platforms to combat biofilms associated with chronic wounds.

Highly efficient in crystallo energy transduction of light to work.

Various mechanical effects have been reported with molecular materials, yet organic crystals capable of multiple dynamic effects are rare, and at present, their performance is worse than some of the common actuators. Here, we report a confluence of different mechanical effects across three polymorphs of an organic crystal that can efficiently convert light into work. Upon photodimerization, acicular crystals of polymorph I display output work densities of about 0.06-3.94 kJ m-3, comparable to ceramic piezoelectric actuators. Prismatic crystals of the same form exhibit very high work densities of about 1.5-28.5 kJ m-3, values that are comparable to thermal actuators. Moreover, while crystals of polymorph II roll under the same conditions, crystals of polymorph III are not photochemically reactive; however, they are mechanically flexible. The results demonstrate that multiple and possibly combined mechanical effects can be anticipated even for a simple organic crystal.

Long-term immunogenicity and safety of heterologous boosting with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants who had received two or three doses of inactivated vaccine.

The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites. Adverse events (AEs) through 30 days and serious AEs during the study were collected. Live-virus and pseudovirus neutralizing antibody (Nab), binding antibody (immunoglobulin G [IgG]) and cellular immunity were tested through 180 days. Solicited all, injection-site and systemic AEs were reported by 618 (61.8%), 498 (49.8%), and 386 (38.6%) participants, respectively. Most AEs were grade 1. The two groups had similar safety profile. No vaccination-related SAEs were reported. Robust wild-type (WT) live-virus Nab response was elicited with peak geometric mean titers (GMTs) of 3769.5 (Group A) and 5994.7 (Group B) on day 14, corresponding to 1602.5- and 290.8-fold increase versus baseline, respectively. The BA.5 live-virus Nab GMTs were 87.7 (Group A) and 93.2 (Group B) on day 14. All participants seroconverted for WT live-virus Nab. Robust pseudovirus Nab and IgG responses to wild type and BA.5 were also elicited. ELISpot assay showed robust cellular immune response, which was not obviously affected by virus variation. In conclusion, SYS6006 heterologous boosting demonstrated long-term good safety and immunogenicity in participants who had received two or three doses of SARS-CoV-2 inactivated vaccine.

Interfacial Engineering Boosting the Activity and Stability of MIL-53(Fe) toward Electrocatalytic Nitrogen Reduction.

The electrochemical nitrogen reduction reaction (eNRR) has emerged as a promising strategy for green ammonia synthesis. However, it suffers unsatisfactory reaction performance owing to the low aqueous solubility of N2 in aqueous solution, the high dissociation energy of N≡N, and the unavoidable competing hydrogen evolution reaction (HER). Herein, a MIL-53(Fe)@TiO2 catalyst is designed and synthesized for highly efficient eNRR. Relative to simple MIL-53(Fe), MIL-53(Fe)@TiO2 achieves a 2-fold enhancement in the Faradaic efficiency (FE) with an improved ammonia yield rate by 76.5% at -0.1 V versus reversible hydrogen electrode (RHE). After four cycles of electrocatalysis, MIL-53(Fe)@TiO2 can maintain a good catalytic activity, while MIL-53(Fe) exhibits a significant decrease in the NH3 yield rate and FE by 79.8 and 82.3%, respectively. Benefiting from the synergetic effect between TiO2 and MIL-53(Fe) in the composites, Fe3+ ions can be greatly stabilized in MIL-53(Fe) during the eNRR process, which greatly hinders the catalyst deactivation caused by the electrochemical reduction of Fe3+ ions. Further, the charge transfer ability in the interface of composites can be improved, and thus, the eNRR activity is significantly boosted. These findings provide a promising insight into the preparation of efficient composite electrocatalysts.

Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

Mi-BMSCs alleviate inflammation and fibrosis in CCl4-and TAA-induced liver cirrhosis by inhibiting TGF-ß/Smad signaling.

Cirrhosis is an aggressive disease, and over 80 % of liver cancer patients are complicated by cirrhosis, which lacks effective therapies. Transplantation of mesenchymal stem cells (MSCs) is a promising option for treating liver cirrhosis. However, this therapeutic approach is often challenged by the low homing ability and short survival time of transplanted MSCs in vivo. Therefore, a novel and efficient cell delivery system for MSCs is urgently required. This new system can effectively extend the persistence and duration of MSCs in vivo. In this study, we present novel porous microspheres with microfluidic electrospray technology for the encapsulation of bone marrow-derived MSCs (BMSCs) in the treatment of liver cirrhosis. Porous microspheres loaded with BMSCs (Mi-BMSCs) exhibit good biocompatibility and demonstrate better anti-inflammatory properties than BMSCs alone. Mi-BMSCs significantly increase the duration of BMSCs and exert potent anti-inflammatory and anti-fibrosis effects against CCl4 and TAA-induced liver cirrhosis by targeting the TGF-ß/Smad signaling pathway to ameliorate cirrhosis, which highlight the potential of Mi-BMSCs as a promising therapeutic approach for early liver cirrhosis.

White light emission in 0D halide perovskite [(CH3)3S]2SnCl6·H2O crystals through variation of doping ns2 ions.

With the rapid development of white LEDs, the research of new and efficient white light emitting materials has attracted increasing attention. Zero dimensional (0D) organic-inorganic hybrid metal halide perovskites with superior luminescent property are promising candidates for LED application, due to their abundant and tailorable structure. Herein, [(CH3)3S]2SnCl6·H2O is synthesized as a host for dopant ions Bi3+ and Sb3+. The Sb3+ doped, or Bi3+/Sb3+ co-doped, [(CH3)3S]2SnCl6·H2O has a tunable optical emission spectrum by means of varying dopant ratio and excitation wavelength. As a result, we can achieve single-phase materials suitable for emission ranging from cold white light to warm white light. The intrinsic mechanism is examined in this work, to clarify the dopant effect on the optical properties. The high stability of title crystalline material, against water, oxygen and heat, makes it promising for further application.

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer.

BACKGROUND: Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. METHODS: A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. RESULTS: Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. CONCLUSION: This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.

Pharmacokinetics, withdrawal period and risk assessment of enrofloxacin in the northern snakehead (Channa argus) following bath administration.

Enrofloxacin (ENR) is widely used in aquaculture practice, but little is known about its pharmacokinetic, withdrawal period and dietary risk in fish via bath administration. The purpose of this study was to provide data support for the use of ENR bath therapy in the northern snakehead (Channa argus). The pilot study was carried out to evaluate the therapy concentrations of ENR in northern snakehead with immersion concentrations ranged from 5 to 40 mg/L for 6 h. Based on results of the pilot study, an ENR immersion concentration of 20 mg/L was used for the formal experiment. At this dose, the peak concentrations of ENR in plasma, muscle plus skin, liver and kidney were 4.85, 4.55, 3.87 and 7.42 µg/mL (or g), respectively. According to the AUC0-∞ values, the distribution of ENR in northern snakehead followed the order of kidney > plasma > liver > muscle + skin. The elimination of ENR in northern snakehead was very slow, the half-lives (T1/2λz ) were up to 90.31, 85.5, 104.56 and 120.9 h in plasma, muscle plus skin, liver and kidney, respectively. Ciprofloxacin (CIP) was not detected in any samples in the pilot study and was only occasionally detected in muscle plus skin and liver samples in formal experiment. Based on the calculated PK/PD index AUC/MIC and Cmax /MIC, the current bath treatment regimen will have a good therapeutic effect on infections caused by bacteria with MIC below 0.6 µg/mL. The dietary risk assessment suggested that there was a dietary risk (Hazard Quotients > 10%) until day 6 after bath treatment. It is mandatory for ENR to maintain a withdrawal period of at least 450°C-day in northern snakehead after bath treatment ceased.

Fabrication of targeted and pH responsive lysozyme-hyaluronan nanoparticles for 5-fluorouracil and curcumin co-delivery in colorectal cancer therapy.

Green nanotechnology is considered a promising method to construct functional materials with significant anticancer activity, while overcoming the shortcomings of traditional synthesis process complexity and high organic solvents consumption. Thus, in this study, we report for the first time the rational design and green synthesis of functionalized 5-fluorouracil and curcumin co-loaded lysozyme-hyaluronan composite colloidal nanoparticles (5-Fu/Cur@LHNPs) for better targeted colorectal cancer therapy with minimized side effects. The functionalized 5-Fu/Cur@LHNPs exhibit stabilized particle size (126.1 nm) with excellent homogeneity (PDI = 0.1), favorable colloidal stabilities, and excellent re-dispersibility. In vitro cell experiments illustrate that the cellular uptake of 5-Fu/Cur@LHNPs was significantly improved and further promoted a higher apoptosis ratio of HCT-116 cells. Compared with the control group, the 5-Fu/Cur@LHNPs formulation group achieved effective inhibition (60.1 %) of colorectal tumor growth. The alcohol-free self-assembly method to construct 5-Fu/Cur@LHNPs is simple and safe for a translational chemotherapy drug, also to promote more robust delivery systems for treating colorectal cancer.

Temperature-Immune, Wide-Range Flexible Robust Pressure Sensors for Harsh Environments.

Flexible pressure sensors possess vast potential for various applications such as new energy batteries, aerospace engines, and rescue robots owing to their exceptional flexibility and adaptability. However, the existing sensors face significant challenges in maintaining long-term reliability and environmental resilience when operating in harsh environments with variable temperatures and high pressures (∼MPa), mainly due to possible mechanical mismatch and structural instability. Here, we propose a composite scheme for a flexible piezoresistive pressure sensor to improve its robustness by utilizing material design of near-zero temperature coefficient of resistance (TCR), radial gradient pressure-dividing microstructure, and flexible interface bonding process. The sensing layer comprising multiwalled carbon nanotubes (MWCNTs), graphite (GP), and thermoplastic polyurethane (TPU) was optimized to achieve a near-zero temperature coefficient of resistance over a temperature range of 25-70 °C, while the radial gradient microstructure layout based on pressure division increases the range of pressure up to 2 MPa. Furthermore, a flexible interface bonding process introduces a self-soluble transition layer by direct-writing TPU bonding solution at the bonding interface, which enables the sensor to achieve signal fluctuations as low as 0.6% and a high interface strength of up to 1200 kPa. Moreover, it has been further validated for its capability of monitoring the physiological signals of athletes as well as the long-term reliable environmental resilience of the expansion pressure of the power cell. This work demonstrates that the proposed scheme sheds new light on the design of robust pressure sensors for harsh environments.

Comparative efficacies of various corticosteroids for preventing postextubation stridor and reintubation: a systematic review and network meta-analysis.

Objectives: We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation. Methods: We searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation. Results: The 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22-0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11-0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08-0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24-1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13-0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25-0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results. Conclusions: Methylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.

Natural Aldehyde-Chitosan Schiff Base: Fabrication, pH-Responsive Properties, and Vegetable Preservation.

The aim of the present work was to fabricate Schiff base compounds between chitosan and aldehydes and use the resultant aldehyde-chitosan Schiff bases for broccoli preservation. Using an element analyzer, the degree of substitution was calculated as 68.27-94.65%. The aldehyde-chitosan Schiff bases showed acidic sensitivity to rapid hydrolysis for releasing aldehyde at a buffer solution of pH 4-6, in which more than 39% of the aldehydes were released within 10 h. The release of aldehydes endows the aldehyde-chitosan Schiff bases with a better antibacterial activity at pH 5 than at pH 7. In a simulated CO2 (5-15%) atmosphere with high humidity (92%), the hydrolysis of imine bonds (C=N) was triggered and continuously released aldehyde, even without direct contact with the aqueous phase. The application of aldehyde-chitosan Schiff bases significantly extended the shelf life of broccoli from 4 d to 5-7 d and decreased the weight loss of broccoli during storage. In summary, the fabrication of aldehyde-chitosan Schiff bases and the strategy of using pH-response imine bond (C=N) hydrolysis (thus releasing aldehyde to kill microorganisms) were feasible for use in developing EO-incorporated intelligent food packages for vegetable preservation.

Laccase-Induced Gelation of Sugar Beet Pectin-Curcumin Nanocomplexes Enhanced by Genipin Crosslinking.

Research on the use of polysaccharides as hydrophobic bioactive carriers instead of proteins is still scarce. Sugar beet pectin (SBP) contains a small amount of protein and is a potential carrier for loading curcumin. In this work, SBP encapsulation, genipin crosslinking, and laccase-induced gelation were used to develop novel jelly food and improve the stability of curcumin without the incorporation of oil. By mixing the SBP solution (40 mg/mL) with curcumin powder (25 mg/mL SBP solution), an SBP-curcumin complex (SBP-Cur) was fabricated with a loading amount of 32 mg/g SBP, and the solubility of curcumin improved 116,000-fold. Fluorescence spectroscopy revealed that hydrophobic interactions drove the complexation of curcumin and SBP. Crosslinked by genipin (10 mM), SBP-Cur showed a dark blue color, and the gel strength of laccase-catalyzed gels was enhanced. Heating and UV radiation tests suggested that the genipin crosslinking and gelation strategies substantially improved the stability of curcumin. Because of the unique UV-blocking capacity of blue pigment, crosslinked samples retained 20% more curcumin than control samples. With the enhanced stability of curcumin, the crosslinked SBP-curcumin complexes could be a functional food ingredient used in functional drinks, baked food, and jelly food.