Applications of physical and chemical treatments in plant-based gels for food 3D printing.

Extrusion-based three-dimensional (3D) printing has been extensively studied in the food manufacturing industry. This technology places particular emphasis on the rheological properties of the printing ink. Gel system is the most suitable ink system and benefits from the composition of plant raw materials and gel properties of multiple components; green, healthy aspects of the advantages of the development of plant-based gel system has achieved a great deal of attention. However, the relevant treatment technologies are still only at the laboratory stage. With a view toward encouraging further optimization of ink printing performance and advances in this field, in this review, we present a comprehensive overview of the application of diverse plant-based gel systems in 3D food printing and emphasize the utilization of different treatment methods to enhance the printability of these gel systems. The treatment technologies described in this review are categorized into three distinct groups, physical, chemical, and physicochemical synergistic treatments. We comprehensively assess the specific application of these technologies in various plant-based gel 3D printing systems and present valuable insights regarding the challenges and opportunities for further advances in this field.

Brain topology improved spiking neural network for efficient reinforcement learning of continuous control.

The brain topology highly reflects the complex cognitive functions of the biological brain after million-years of evolution. Learning from these biological topologies is a smarter and easier way to achieve brain-like intelligence with features of efficiency, robustness, and flexibility. Here we proposed a brain topology-improved spiking neural network (BT-SNN) for efficient reinforcement learning. First, hundreds of biological topologies are generated and selected as subsets of the Allen mouse brain topology with the help of the Tanimoto hierarchical clustering algorithm, which has been widely used in analyzing key features of the brain connectome. Second, a few biological constraints are used to filter out three key topology candidates, including but not limited to the proportion of node functions (e.g., sensation, memory, and motor types) and network sparsity. Third, the network topology is integrated with the hybrid numerical solver-improved leaky-integrated and fire neurons. Fourth, the algorithm is then tuned with an evolutionary algorithm named adaptive random search instead of backpropagation to guide synaptic modifications without affecting raw key features of the topology. Fifth, under the test of four animal-survival-like RL tasks (i.e., dynamic controlling in Mujoco), the BT-SNN can achieve higher scores than not only counterpart SNN using random topology but also some classical ANNs (i.e., long-short-term memory and multi-layer perception). This result indicates that the research effort of incorporating biological topology and evolutionary learning rules has much in store for the future.

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats.

Cerebral ischemia was one of the leading causes of mortality and disability worldwide. Extracellular matrix (ECM) hydrogel held great potential to replace volumetric brain tissue loss following ischemic injury but with limited regenerative effect for functional restoration when implanted alone. In the present study, an engineered basic fibroblast growth factor (EBP-bFGF) was constructed, which fused a specific ECM-binding peptide (EBP peptide) with bFGF. The recombinant EBP-bFGF showed typical binding capacity with ECM without affecting the bioactivity of bFGF both in vitro and in vivo. Furthermore, the EBP-bFGF was used for bioactive modification of ECM hydrogel to repair cerebral ischemia. The combination of EBP-bFGF and ECM hydrogels could realize the sustained release of bFGF in the ischemic brain and improve the regenerative effect of ECM, which protected the survival of neurons, enhanced angiogenesis, and decreased the permeability of blood-brain barrier, ultimately promoted the recovery of motor function. In addition, transcriptome analysis revealed neuregulin-1/AKT pathway involved in this process. Therefore, EBP-bFGF/ECM hydrogel would be a promising therapeutic strategy for cerebral ischemia.

Spike-based dynamic computing with asynchronous sensing-computing neuromorphic chip.

By mimicking the neurons and synapses of the human brain and employing spiking neural networks on neuromorphic chips, neuromorphic computing offers a promising energy-efficient machine intelligence. How to borrow high-level brain dynamic mechanisms to help neuromorphic computing achieve energy advantages is a fundamental issue. This work presents an application-oriented algorithm-software-hardware co-designed neuromorphic system for this issue. First, we design and fabricate an asynchronous chip called "Speck", a sensing-computing neuromorphic system on chip. With the low processor resting power of 0.42mW, Speck can satisfy the hardware requirements of dynamic computing: no-input consumes no energy. Second, we uncover the "dynamic imbalance" in spiking neural networks and develop an attention-based framework for achieving the algorithmic requirements of dynamic computing: varied inputs consume energy with large variance. Together, we demonstrate a neuromorphic system with real-time power as low as 0.70mW. This work exhibits the promising potentials of neuromorphic computing with its asynchronous event-driven, sparse, and dynamic nature.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Campylotropis xinfeniae (Fabaceae, Papilionoideae), a new species from Yunnan, China, based on morphological and molecular evidence.

Campylotropis xinfeniae, a new species from the dry-hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3-foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.

Efficacy of Shenglin decoction in preventing acute severe lymphocytopenia in patients with non-small cell lung cancer undergoing concurrent chemoradiotherapy: a study protocol for a randomized controlled trial.

Background: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL. Methods: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms. Discussion: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT. Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).

Assisted reproductive technology and neurodevelopment in children at one year of age: a longitudinal birth cohort study.

BACKGROUND: With remarkable advancements in assisted reproductive technology (ART), the number of ART conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial. OBJECTIVE: The aim of this study was to investigate the association between ART use and neurodevelopment in children at one year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children. STUDY DESIGN: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3,531 pregnancies with 3,840 cohort children who completed neurodevelopment assessment at one year of age, including 1,906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children. RESULTS: Among singletons, ART use was associated with a 24%-34% decrease in the risk for noncompetent development in three domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons. CONCLUSIONS: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation.

Correction: Aptamer AS1411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

[This corrects the article DOI: 10.1039/D3MD00752A.].

Aptamer AS411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

G-quadruplex (G4) aptamers that can competitively binding protein with oncogene promoter G4 hold promise for cancer treatment. In this study, a neutral cytidinyl lipid, DNCA, was shown to transfect and deliver G4 aptamers (AS1411, TBA) into tumour cells, including multidrug-resistant tumour cells, and their nuclear localizations were clearly detected. Both AS1411/DNCA and TBA/DNCA showed excellent antitumour efficacies in the drug-resistant non-small cell lung cancer cell line A549/TXL at a low concentration (100 nM). Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as a new target of AS1411 and TBA. The binding affinities were measured, and the Kd values of AS1411/hnRNP A1 and TBA/hnRNP A1 were 17.5 nM and 21.1 nM, respectively. Then the expression of KRAS mRNA in A549/TXL cells was found to be higher than that in A549 cells, and KRAS mRNA was reduced by approximately 40% after administration of AS1411 or TBA in A549/TXL cells. Further, it was confirmed for the first time that AS1411 targeted not only hnRNP A1 but also the KRAS promoter/hnRNP A1 complexes. And although TBA cannot target the KRAS promoter/hnRNP A1 complexes, the biolayer interferometry (BLI) experiment showed that TBA and AS1411 have similar effects on several key proteins in tumour cells, especially hnRNP A1. Molecular docking and molecular dynamics simulation showed that AS1411 and the KRAS promoter bound to the same domain of hnRNP A1 protein, while TBA bound to another domain.

Cellulose-based adsorbent using in mercury detection and removal from water via an efficient grafting strategy of fluorometric sensors by click reaction.

Mercury pollution in waters attracts lots of attention due to its serious toxicity and high bioenrichment and many efforts have been devoted in the development of adsorbents for mercury detection and removal. Herein, a cellulose-based adsorbent Cell-TriA-HQ is functionalized with quinoline fluorophore by covalent immobilization through "Click reaction" with high yield. In addition to the admirable adsorptive performance, the prepared adsorbent exhibits excellent selectivity and sensitivity towards Hg (II) in water that the detection limit for Hg (II) is determined to be as low as 1.92 × 10-7 M. The sensitive fluorescence enhancement response is considered to be resulted from the inhibition of photo-induced electron transfer between triazole and quinoline groups and the reinforcement of structural rigidity. The easy manipulation along with excellent performance of adsorption capacity, detective ability and reusability for the multifunctional adsorbent makes it potential in mercury monitoring and removal from aqueous solutions in the field of water treatment.

Construction of cellulose-based hybrid hydrogel beads containing carbon dots and their high performance in the adsorption and detection of mercury ions in water.

Cellulose-based adsorbents have been extensively developed in heavy metal capture and wastewater treatment. However, most of the reported powder adsorbents suffer from the difficulties in recycling due to their small sizes and limitations in detecting the targets for the lack of sensitive sensor moieties in the structure. Accordingly, carbon dots (CDs) were proposed to be encapsulated in cellulosic hydrogel beads to realize the simultaneous detection and adsorption of Hg (II) in water due to their excellent fluorescence sensing performance. Besides, the molding of cellulose was beneficial to its recycling and further reduced the potential environmental risk generated by secondary pollution caused by adsorbent decomposition. In addition, the detection limit of the hydrogel beads towards Hg (II) reached as low as 8.8 × 10-8 M, which was below the mercury effluent standard declared by WHO, exhibiting excellent practicability in Hg (II) detection and water treatment. The maximum adsorption capacity of CB-50 % for Hg (II) was 290.70 mg/g. Moreover, the adsorbent materials also had preeminent stability that the hydrogel beads could maintain sensitive and selective sensing performance towards Hg (II) after 2 months of storage. Additionally, only 3.3% of the CDs leaked out after 2 weeks of immersion in water, ensuring the accuracy of Hg (II) evaluation. Notably, the adsorbent retained over 80% of its original adsorption capacity after five consecutive regeneration cycles, underscoring its robustness and potential for sustainable environmental applications.

Superconductivity above 105 K in Nonclathrate Ternary Lanthanum Borohydride below Megabar Pressure.

Hydrides are promising candidates for achieving room-temperature superconductivity, but a formidable challenge remains in reducing the stabilization pressure below a megabar. In this study, we successfully synthesized a ternary lanthanum borohydride by introducing the nonmetallic element B into the La-H system, forming robust B-H covalent bonds that lower the pressure required to stabilize the superconducting phase. Electrical transport measurements confirm the presence of superconductivity with a critical temperature (Tc) of up to 106 K at 90 GPa, as evidenced by zero resistance and Tc shift under an external magnetic field. X-ray diffraction and transport measurements identify the superconducting compound as LaB2H8, a nonclathrate hydride, whose crystal structure remains stable at pressures as low as ∼ half megabar (59 GPa). Stabilizing superconductive stoichiometric LaB2H8 in a submegabar pressure regime marks a substantial advancement in the quest for high-Tc superconductivity in polynary hydrides, bringing us closer to the ambient pressure conditions.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Quantification for photochemical loss of volatile organic compounds upon ozone formation chemistry at an industrial city (Zibo) in North China Plain.

Volatile organic compounds (VOCs) are consumed by photochemical reactions during transport, leading to inaccuracies in estimating the local ozone (O3) formation mechanism and its subsequent strategy for O3 attainment. To comprehensively quantify the deviations in O3 formation mechanism by consumed VOCs (C-VOCs), a 5-month field campaign was conducted in a typical industrial city in Northern China over incorporating a 0-D box model (implemented with MCMv3.3.1). The averaged C-VOCs concentration was 6.8 ppbv during entire period, and Alkenes accounted for 62% dominantly. Without considering C-VOCs, the relative incremental reactivity (RIR) of anthropogenic VOCs (AVOC, overestimated by 68%-75%) and NOx (underestimated by 137%-527%) demonstrated deviations at multiple scenarios, and the RIR deviations for precursors in High-O3-periods (HOP) were lower than Low-O3-periods (LOP). The RIR deviations from individual species involved C-VOCs calculation did not impact the identification for the high-ranking-RIR AVOC species but non-negligible. Monthly comparisons showed that higher C-VOCs concentrations would lead to higher RIR deviations. The daily maximum of net Ox production rate (P(Ox)) and the regional transport Ox (Trans(Ox)) without C-VOCs were underestimated by 56%-194% and 81%-243%, respectively. After considering C-VOCs, the contribution of HO2+NO for Ox gross production (G(Ox)) decreased by 7% (LOP) and 7% (HOP), but OH + NO2 for Ox destruction (D(Ox)) decreased by 16% (LOP) and 23% (HOP), and alkenes + O3 increased for D(Ox) by 12% (LOP) and 22% (HOP). This implies that VOCs-NOx-O3 sensitivity was deviated between with/without C-VOCs, and severe O3 pollution rendered deviations in O3 formation, especially via NOx-driving chemistry. Based on RIR(NOx)/RIR(AVOC) with/without C-VOCs, the sensitivity regime shifted from VOCs-limited (-0.93) to transition (1.38) at LOP, and from VOCs-limited (0.19) to NOx-limited (3.79) at HOP. Our results reflected that the NOx limitation degree was underestimated without constraint C-VOCs, especially HOP, and provided implication to more precise O3 pollution control strategies.

Associations between tobacco inhalation and semen parameters in men with primary and secondary infertility: a cross-sectional study.

Objective: To examine the impact of tobacco smoking on seminal parameters in men with both primary and secondary infertility. Methods: This cross-sectional study analyzed 1938 infertile men from China who were categorized as nonsmokers (n=1,067) and smokers (n=871), with the latter group further divided into moderate smokers (1-10 cigarettes per day) (n=568) and heavy smokers (>10 cigarettes per day) (n=303). We assessed semen volume, concentration, total sperm count, progressive motility, and normal morphology following World Health Organization (WHO 2010) guidelines. A logistic regression model was used to analyze the relationships between smoking and seminal parameters while also controlling for lifestyle factors. Results: The analysis demonstrated a statistically significant correlation between smoking and adverse seminal parameters in both primary and secondary infertility patients. Specifically, primary infertile men who smoked had a lower semen concentration, with heavy smokers showing a median sperm concentration of 59.2×10^6/ml compared to 68.6×10^6/ml in nonsmokers (P=0.01). The secondary infertile men who smoked exhibited reduced forward sperm motility, with heavy smokers demonstrating a median progressive motility of 44.7%, which was significantly lower than the 48.1% observed in nonsmokers (P=0.04). Conclusion: Smoking is significantly associated with detrimental effects on seminal parameters in infertile men, thus highlighting the need for cessation programs as part of fertility treatment protocols. Encouraging smoking cessation could substantially improve semen quality and fertility outcomes in this population.

Factor B inhibitor iptacopan for the treatment of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, complement-mediated hemolytic anemia with a variety of manifestations. Currently, the methods for treating PNH include anti-C5 treatments (eculizumab and ravulizumab) and pegcetacoplan (a targeted C3 inhibitor). On December 5, 2023, the US FDA approved a factor B inhibitor called Fabhalta® (iptacopan), previously known as LNP023, for the treatment of adult patients with PNH, including those who have previously received anti-C5 therapy. The main objective of this review was to elucidate the clinical efficacy and safety of the newly approved factor B inhibitor, iptacopan. Iptacopan plays a proximal role in the alternative complement pathway to control extravascular hemolysis mediated by C3b and intravascular hemolysis mediated by terminal complement. The recommended dosage is 200 mg orally twice daily. The 24-week results of the pivotal phase III open-label trial, APPLY-PNH, demonstrated that among PNH patients who had previously received anti-C5 therapy, 51/60 (estimated percentages 82%) of patients in the iptacopan group showed an increase in hemoglobin of ≥2 g/dL compared to 0/35 (estimated percentages 2%) in the standard treatment group, also, 69% of iptacopan-treated patients achieved hemoglobin levels ≥12 g/dL, while no patients in the standard treatment group reached this level (both p < 0.001). The 48-week results were similar to those observed at 24 weeks. The most common adverse events were headache, infection and diarrhea. There were almost no clinical breakthrough hemolysis. Trials evaluating the long-term safety and efficacy of iptacopan are currently recruiting.

Earthworm gut bacteria facilitate cadmium immobilization through the formation of CdS nanoparticles.

Gut bacteria of earthworm Amynthas hupeiensis exhibit significant potential for the in-situ remediation of cadmium (Cd)-contaminated soil. However, the mechanisms by which these gut bacteria immobilize and tolerate Cd remain elusive. The composition of the gut bacterial community was characterized by high-throughput sequencing. Cd-tolerant bacteria were isolated from the gut, and their roles in Cd immobilization, as well as their tolerance mechanisms, were explored through chemical characterization and transcriptome analysis. The predominant taxa in the gut bacterial community included unclassified Enterobacteriaceae, Citrobacter, and Bacillus, which were distinctly different from those in the surrounding soil. Notably, the most Cd-tolerant gut bacterium, Citrobacter freundii DS strain, immobilized 63.61% of Cd2+ within 96 h through extracellular biosorption and intracellular bioaccumulation of biosynthetic CdS nanoparticles, and modulation of solution pH and NH4+ concentration. Moreover, the characteristic signals of CdS were also observed in the gut content of A. hupeiensis when the sterilized Cd-contaminated soil was inoculated with C. freundii. The primary pathways involved in the response of C. freundii to Cd stress included the regulation of ABC transporters, bacterial chemotaxis, cell motility, oxidative phosphorylation, and two-component system. In conclusion, C. freundii facilitates Cd immobilization both in vitro and in vivo, thereby enhancing the host earthworm's adaptation to Cd-contaminated soil.

A dual-mode label-free electrochemical immunosensor for ultrasensitive detection of procalcitonin by on-site vulcanization of dual-MOF heterostructure.

Detection of procalcitonin (PCT) is crucial for the early identification of sepsis. PCT is primarily utilized in the multiple diagnosis of bacterial and viral illnesses along with to guide the application of antibiotics. Considering their advantages of high specificity and straightforward usage, electrochemical immunosensors offer significant application prospects in the detection of disease indicators. A dual-mode electrochemical immunosensor was constructed in this study to reliably identify PCT. In light of the synergistic effect of the dual-MOF derived heterostructure, the immunosensor demonstrating excellent square wave voltammetry (SWV) signals as well as significant catalytic activity for the H2O2 redox process. In addition to maintaining a low detection limit (SWV: 0.31 fg/mL and i-t: 0.098 fg/mL), the immunosensor offers an extensive linear response range (0.000001-100 ng/mL). The excellent performance is on account of the introduction of the local on-site sulfurized dual-MOF heterostructure with abundant metal chalcogenides/MOF interfaces, which boosts the specific surface area, offers an abundance of active sites, enhances conductivity, and raises catalytic activity. Furthermore, the immunosensor exhibits outstanding specificity, stability and reproducibility for the determination of PCT in serum, which is of great crucial for the clinical screening and diagnosis of sepsis.