Soil colloids can significantly enhance spreading of polybromodiphenyl ethers in groundwater by serving as an effective carrier.

Polybromodiphenyl ethers (PBDEs), the widely used flame retardants, are common contaminants in surface soils at e-waste recycling sites. The association of PBDEs with soil colloids has been observed, indicating the potential risk to groundwater due to colloid-facilitated transport. However, the extent to which soil colloids may enhance the spreading of PBDEs in groundwater is largely unknown. Herein, we report the co-transport of decabromodiphenyl ester (BDE-209) and soil colloids in saturated porous media. The colloids released from a soil sample collected at an e-waste recycling site in Tianjin, China, contain high concentration of PBDEs, with BDE-209 being the most abundant conger (320 ± 30 mg/kg). The colloids exhibit relatively high mobility in saturated sand columns, under conditions commonly observed in groundwater environments. Notably, under all the tested conditions (i.e., varying flow velocity, pH, ionic species and ionic strength), the mass of eluted BDE-209 correlates linearly with that of eluted soil colloids, even though the mobility of the colloids varies markedly depending on the specific hydrodynamic and solution chemistry conditions involved. Additionally, the mass of BDE-209 retained in the columns also correlates strongly with the mass of retained colloids. Apparently, the PBDEs remain bound to soil colloids during transport in porous media. Findings in this study indicate that soil colloids may significantly promote the transport of PBDEs in groundwater by serving as an effective carrier. This might be the reason why the highly insoluble and adsorptive PBDEs are found in groundwater at some PBDE-contaminated sites.

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss.

JOURNAL/nrgr/04.03/01300535-202505000-00030/figure1/v/2024-07-28T173839Z/r/image-tiff Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction. However, there are currently no effective pharmacological interventions for patients with noise-induced hearing loss. Here, we present evidence suggesting that the lysine-specific demethylase 1 inhibitor-tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss, and elucidate its underlying regulatory mechanisms. We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 dB for 4 hours. We found that tranylcypromine treatment led to the upregulation of Sestrin2 (SESN2) and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine. The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click, 4, 8, and 16 kHz frequencies compared with the noise exposure group treated with saline. These findings indicate that tranylcypromine treatment resulted in increased SESN2, light chain 3B, and lysosome-associated membrane glycoprotein 1 expression after noise exposure, leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3, thereby reducing noise-induced hair cell loss. Additionally, immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway. Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domain-containing 3 (NLRP3) production. In conclusion, our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2, which induced autophagy, thereby restricting NLRP3-related inflammasome signaling, alleviating cochlear hair cell loss, and protecting hearing function. These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

Precooked state based on protein denaturation kinetics impacts moisture status, protein oxidation and texture of prepared chicken breast.

The quality of meat in prepared dishes deteriorates due to excessive protein denaturation resulting from precooking, freezing, and recooking. This study aimed to link the precooked state with chicken breast's recooked quality. Cooked Value (CV), based on protein denaturation kinetics, was established to indicate the doneness of meat during pre-heating. The effects of CVs after pre-heating on recooked qualities were investigated compared to fully pre-heated samples (control). Mild pre-heating reduced water migration and loss. While full pre-heating inhibited protein oxidation during freezing, intense oxidation during pre-heating led to higher oxidation levels. Surface hydrophobicity analysis revealed that mild pre-heating suppressed aggregation during recooking. These factors contributed to a better texture and microstructure of prepared meat with mild pre-heating. Finally, a potential mechanism of how pre-heating affects final qualities was depicted. This study underlines the need for finely controlling the industrial precooking process to regulate the quality of prepared meat.

"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Partition coefficient screening - An effective approach for finding the best conditions for byproduct removal as demonstrated by a bispecific antibody purification case.

In recombinant protein purification, differences in isoelectric point (pI)/surface charge and hydrophobicity between the product and byproducts generally form the basis for separation. For bispecific antibodies (bsAbs), in many cases the physicochemical difference between product and byproducts is subtle, making byproduct removal considerably challenging. In a previous report, with a bsAb case study, we showed that partition coefficient (Kp) screening for the product and byproducts under various conditions facilitated finding conditions under which effective separation of two difficult-to-remove byproducts was achieved by anion exchange (AEX) chromatography. In the current work, as a follow-up study, we demonstrated that the same approach enabled identification of conditions allowing equally good byproduct removal by mixed-mode chromatography with remarkably improved yield. Results from the current and previous studies proved that separation factor determination based on Kp screening for product and byproduct is an effective approach for finding conditions enabling efficient and maximum byproduct removal, especially in challenging cases.

A screening model for predicting the potential of soil colloids-enhanced leaching of hydrophobic organic contaminants to groundwater at contaminated sites.

Modeling the fate and transport of organic pollutants at contaminated sites is critical for risk assessment and management practices, such as establishing realistic cleanup standards or remediation endpoints. Against the conventional wisdom that highly hydrophobic persistent organic pollutants (POPs) (e.g., polybrominated diphenyl ethers and polycyclic aromatic hydrocarbons) in surface soils are essentially immobile, mounting evidence has demonstrated the potential of these contaminants leaching into the groundwater, due to enhanced transport by soil colloids. Here, we develop a Colloids-Enhanced Transport (CET) model, which can be used as a simple screening tool to predict the leaching potential of POPs into groundwater, as mediated by soil colloids. The CET model incorporates several processes, including the release of POPs-bearing colloids into the porewater, the vertical transport of colloids and associated POPs in the vadose zone, the mixing of POPs-containing soil leachate with groundwater, and the migration of POPs-bearing colloids in saturated zone. Thus, using parameters that can be easily obtained (e.g., annual rainfall, soil type, and common hydrogeological properties of the subsurface porous media), the CET model can estimate the concentrations of POPs in the saturated zone from the observed POPs concentrations in surface or shallow subsurface zones. The CET model can also be used to derive soil quality standards or cleanup endpoints by back-calculating soil concentrations based on groundwater protection limits.

Preferential association of PBDEs and PAHs with mineral particles vs. dissolved organic carbon: Implications for groundwater contamination at e-waste sites.

Polybrominated biphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) are commonly detected contaminants at e-waste recycling sites. Against the conventional wisdom that PBDEs and PAHs are highly immobile and persist primarily in shallow surface soils, increasing evidence shows that these compounds can leach into the groundwater. Herein, we compare the leachabilities of PBDEs vs. PAHs from contaminated soils collected at an e-waste recycling site in Tianjin, China. Considerable amounts of BDE-209 (0.3-2 ng/L) and phenanthrene (42-106 ng/L), the most abundant PBDE and PAH at the site, are detected in the effluents of columns packed with contaminated soils, with the specific concentrations varying with hydrodynamic and solution chemistry conditions. Interestingly, the leaching potential of BDE-209 appears to be closely related to the release of colloidal mineral particles, whereas the leachability of phenanthrene correlates well with the concentration of dissolved organic carbon in the effluent, but showing essentially no correlation with the concentration of mineral particles. The surprisingly different trends of the leachability observed between BDE-209 and phenanthrene is counterintuitive, as PBDEs and PAHs often co-exist at e-waste recycling sites (particularly at the sites wherein incineration is being practiced) and share many similarities in terms of physicochemical properties. One possible explanation is that due to its extremely low solubility, BDE-209 predominantly exists in free-phase (i.e., as solid (nano)particles), whereas the more soluble phenanthrene is mainly sorbed to soil organic matter. Findings in this study underscore the need to better understand the mobility of highly hydrophobic organic contaminants at contaminated sites for improved risk management.

Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity.

The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4. Purified equine polyclonal IgG provided protection against Omicron XBB.1.5 virus in the K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based nanoparticle vaccines can rapidly produce a broad and protective sarbecovirus response in the equine model and that equine serum has therapeutic potential against emerging SARS-CoV-2 VoC and diverse sarbecoviruses, presenting a possible alternative or supplement to monoclonal antibody immunotherapies.

Arbuscular mycorrhizal fungi improve the disease resistance of Lycium barbarum to root rot by activating phenylpropane metabolism.

Root rot is one of the common diseases of Lycium barbarum. Pathogens can cause devastating disasters to plants after infecting host plants. This study investigated the effect of arbuscular mycorrhizal fungi (AMF) Rhizophagus intraradices inoculation on phenylpropane metabolism in L. barbarum and evaluated its resistance to root rot. The experiment was set up with AMF inoculation treatments (inoculated or not) and root rot pathogen-Fusarium solani inoculation treatments (inoculated or not). The results showed that AMF was able to form a symbiosis with the root system of L. barbarum, thereby promoting plant growth significantly and increasing plants' resistance to disease stress. The plant height of AMF-colonized L. barbarum increased by 24.83% compared to non-inoculated diseased plants. After inoculation with AMF, the plant defense response induced by pathogen infection was stronger. When the enzyme activity of the leaves reached the maximum after the onset of mycorrhizal L. barbarum, phenylalanine ammonia-lyase, cinnamic acid-4-hydroxylase, and 4-coumaric acid-CoA ligase increased by 3.67%, 31.47%, and 13.61%, respectively, compared with the non-inoculated diseased plants. The products related to the lignin pathway and flavonoid pathway downstream of phenylpropane metabolism such as lignin and flavonoids were also significantly increased by 141.65% and 44.61% compared to nonmycorrhizal diseased plants. The activities of chitinase and ß-1,3-glucanase increased by 36.00% and 57.96%, respectively. The contents of salicylic acid and jasmonic acid were also 17.7% and 31.63% higher than those of nonmycorrhizal plants in the early stage of plant growth, respectively. The results indicated that AMF significantly promoted plant growth and enhanced disease resistance by increasing enzyme activities and the production of lignin and flavonoids.

In situ studies revealing the effects of Au surfactant on the formation of ultra-thin Ag layers using high-power impulse magnetron sputter deposition.

Introducing metallic nanoparticles, such as Au, on a substrate as a surfactant or wetting inducer has been demonstrated as a simple but effective way to facilitate the formation of ultra-thin silver layers (UTSLs) during the subsequent Ag deposition. However, most studies have paid much attention to the applications of UTSLs assisted by metallic surfactants but neglected the underlying mechanisms of how the metallic surfactant affects the formation of UTSL. Herein, we have applied in situ grazing-incidence wide-/small-angle X-ray scattering to reveal the effects of the Au surfactant or seed layer (pre-deposited Au nanoparticles) on the formation of UTSL by high-power impulse magnetron sputter deposition (HiPIMS) on a zinc oxide (ZnO) thin film. The comprehensive and in-depth analysis of the in situ X-ray scattering data revealed that the pre-deposited Au nanoparticles can act as additional defects or growth cores for the sputtered Ag atoms despite using HiPIMS, which itself forms many nucleation sites. As a result, the formation of a continuous and smooth UTSL is reached earlier in HiPIMS compared with bare ZnO thin films. Based on the mechanism revealed by the in situ measurements, we provide insight into the formation of UTSL and further UTSL-based applications.

Traits estimated when grown alone may underestimate the competitive advantage and invasiveness of exotic species.

Functional differences between native and exotic species, estimated when species are grown alone or in mixtures, are often used to predict the invasion risk of exotic species. However, it remains elusive whether the functional differences estimated by the two methods and their ability to predict species invasiveness (e.g. high abundance) are consistent. We compiled data from two common garden experiments, in which specific leaf area, height, and aboveground biomass of 64 common native and exotic invasive species in China were estimated when grown individually (pot) or in mixtures (field). Exotic species accumulated higher aboveground biomass than natives, but only when grown in field mixtures. Moreover, aboveground biomass and functional distinctiveness estimated in mixtures were more predictive of species persistence and relative abundance in the field mixtures in the second year than those estimated when grown alone. These findings suggest that assessing species traits while grown alone may underestimate the competitive advantage for some exotic species, highlighting the importance of trait-by-environment interactions in shaping species invasion. Therefore, we propose that integrating multi-site or multi-year field surveys and manipulative experiments is required to best identify the key trait(s) and environment(s) that interactively shape species invasion and community dynamics.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. RESULTS: We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] µIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. CONCLUSIONS: Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.

Global traumatic brain injury intracranial pressure: from monitoring to surgical decision.

Traumatic brain injury (TBI) is a significant global public health issue, heavily impacting human health, especially in low-and middle-income areas. Despite numerous guidelines and consensus statements, TBI fatality rates remain high. The pathogenesis of severe TBI is closely linked to rising intracranial pressure (ICP). Elevated intracranial pressure can lead to cerebral herniation, resulting in respiratory and circulatory collapse, and ultimately, death. Managing intracranial pressure (ICP) is crucial in neuro-intensive care. Timely diagnosis and precise treatment of elevated ICP are essential. ICP monitoring provides real-time insights into a patient's condition, offering invaluable guidance for comprehensive management. ICP monitoring and standardization can effectively reduce secondary nerve damage, lowering morbidity and mortality rates. Accurately assessing and using true ICP values to manage TBI patients still depends on doctors' clinical experience. This review discusses: (a) Epidemiological disparities of traumatic brain injuries across countries with different income levels worldwide; (b) The significance and function of ICP monitoring; (c) Current status and challenges of ICP monitoring; (d) The impact of decompressive craniectomy on reducing intracranial pressure; and (e) Management of TBI in diverse income countries. We suggest a thorough evaluation of ICP monitoring, head CT findings, and GCS scores before deciding on decompressive craniectomy. Personalized treatment should be emphasized to assess the need for surgical decompression in TBI patients, offering crucial insights for clinical decision-making.

Enzyme-accelerated catalytic DNA circuits enable rapid and one-pot detection of bacterial pathogens.

Catalytic DNA circuits, serving as signal amplification strategies, can enable simple and accurate detection of pathogenic bacteria in complex matrices but suffer from low reaction rates and depths. Herein, we design an enzyme-accelerated catalytic hairpin assembly (EACHA) in which duplex DNA products are converted into hairpin reactants to continue participating in the next circuit reaction with the assistance of RNase H. Profiting from the high recyclability of the reactants, EACHA exhibits an approximately 37.6-fold enhancement in the rate constant and a two-order-of-magnitude improvement in sensitivity compared to conventional catalytic hairpin assembly (CHA). By integrating an allosteric probe with EACHA, a one-pot method is developed for rapid and direct detection of S. enterica Enteritidis (S. Enteritidis). This method is capable of detecting 15 CFU mL-1 of S. Enteritidis within 20 min, which is superior to that of real-time PCR. By testing 60 milk samples, we demonstrate this method's high accuracy in discriminating contaminated samples, with an area under the curve (AUC) of 0.997. Moreover, this method can be employed to accurately diagnose early-stage infected mice, with an AUC of 1.00 for feces samples and 0.986 for serum samples. Therefore, this study offers a simple and feasible method for identifying pathogens in complex matrices.

Preparation and properties of polydimethylsiloxane-regulated oriented microporous poly (L-lactic acid) biomimetic bone repair materials.

Despite the exceptional biocompatibility and degradability of Poly (L-lactic acid) (PLLA), its brittleness, low melting strength, and poor bone induction makes it challenging to utilize for bone repair. This study used a simple, efficient solid hot drawing (SHD) method to produce high-strength PLLA, using supercritical CO2 (SC-CO2) foaming technology to give PLLA a bionic microporous structure to enhance its toughness, while precisely controlling micropore homogeneity and improving the melt strength by using Polydimethylsiloxane (PDMS). This PDMS-regulated oriented microporous structure resembled that of natural bone, displaying a maximum tensile strength of 165.9 MPa and a maximum elongation at break of 164.2 %. Furthermore, this bionic structure promoted the polarization of mouse bone marrow macrophages (iBMDM), exhibiting a simultaneous pro- and anti-inflammatory effect. This structure also contributed to the adhesion and growth of mouse embryonic fibroblasts (NIH-3 T3), promoting osteogenic differentiation, which paved the way for developing degradable PLLA bone-repair load-bearing materials.

Evaluation of the efficacy and safety of first- and second-line immunotherapy in patients with metastatic colorectal cancer: a systematic review and network meta-analysis based on randomized controlled trials.

Background: A multitude of randomized controlled trials (RCTs) conducted in both the initial and subsequent treatment settings for patients diagnosed with metastatic colorectal cancer (mCRC) have provided clinical evidence supporting the efficacy of immunotherapy with the use of immune checkpoint inhibitors (ICIs). In light of these findings, the U.S. Food and Drug Administration (FDA) has authorized the use of several ICIs in specific subpopulations of mCRC patients. Nevertheless, there remains a dearth of direct comparative RCTs evaluating various treatment options. Consequently, the most effective ICI therapeutic strategy for microsatellite-stable (MSS) subgroup and microsatellite instability (MSI) subgroup in the first- and second-line therapies remains undefined. To address this gap, the present study employs a Bayesian network meta-analysis to ascertain the most effective first- and second-line ICI therapeutic strategies. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, with the retrieval date ranging from the databases' inception to August 20, 2024. A total of 875 studies were identified, and seven were ultimately included in the analysis after a screening process. A systematic review and network meta-analysis were conducted on the basis of the search results. Results: This comprehensive analysis, comprising seven RCTs, evaluated first-line and second-line immunotherapy regimens in 1,358 patients diagnosed with mCRC. The treatments under investigation consisted of five initial treatments, including three focusing on MSS patients and two on MSI patients, as well as two secondary immunotherapy regimens, both focusing on MSS patients. A total of 1051 individuals underwent first-line treatment, while 307 received second-line treatment. The application of ICIs proved to offer varying degrees clinical benefits when compared to standard-of-care therapy alone, both in two subgroups of the first and the second treatment phases. Of particular note is the performance of Nivolumab combination with ipilimumab, which demonstrated superior efficacy in improving progression-free survival (PFS) (HR=0.21; 95% CI, 0.13-0.34),. Moreover, the treatment demonstrated an optimal safety profile, with a relatively low risk of adverse events (OR = 0.33; 95% CI, 0.19-0.56), compared to other first-line treatment modalities for MSI subgroup. Regarding MSS subgroup, the improvement of PFS by Nivolumab plus standard-of-care (SOC) was relatively significant (HR = 0.74; 95% CI, 0.53-1.02). In the realm of second-line therapies for MSS subgroup, the administration of Atezolizumab plus SOC has proven to be an effective approach for prolonging PFS, exhibiting an HR of 0.66 (95% CI, 0.44-0.99). These findings underscore the clinical benefits and safety profiles of ICIs in the treatment of mCRC across various treatment lines. Conclusions: The clinical application of ICIs in both first- and second-line treatment strategies for patients with mCRC yields substantial therapeutic benefits. A detailed assessment in this study indicates that first-line treatment with Nivolumab combination with ipilimumab may represent an efficacious and well-tolerated therapeutic approach for MSI subgroup. In terms of MSS subgroup in first-line therapy, Nivolumab plus SOC may be a relative superior choice. In the context of second-line therapy for MSS subgroup, it is evident that a combination of Atezolizumab and SOC represents a preferable option for enhancing PFS. Furthermore, it is noteworthy that other ICIs treatment regimens also exhibit great value in various aspects, with the potential to inform the development of future clinical treatment guidelines and provide a stronger rationale for the selection of ICIs in both first- and second-line therapeutic strategies for mCRC. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024543400.

Copper-Catalyzed [3 + 2] Annulation of O-Acyl Oximes with p-Hydroquinones for the Synthesis of 5-Hydroxyindoles.

A copper-catalyzed [3 + 2] annulation of O-acyl oximes with 2-electron-withdrawing group substituted p-hydroquinones for the efficient synthesis of polysubstituted 5-hydroxyindoles is developed. Further intramolecular cyclization leads to the concise and rapid construction of several kinds of 3,4- and 4,5-fused polycyclic indoles.

Changes of NLRP3 in serum and cerebrospinal fluid of patients after moderate to severe traumatic brain injury and their predictive values for prognosis.

BACKGROUND: Traumatic brain injury (TBI) remains a major concern for global health. Recent studies have suggested the role of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an inflammatory marker, in the cerebrospinal fluid (CSF) and serum as potential indicators of TBI prognosis. The objective of the study was to characterize NLRP3 as a clinically applicable tool for predicting the outcomes of TBI patients. METHODS: A total of 270 patients with moderate to severe TBI were included in this retrospective analysis. Serum and CSF samples were collected at 1-, 3-, 7-, and 21-day post-injury to measure NLRP3 levels. The prognosis of patients was evaluated after 3 months using the Glasgow Outcome Scale (GOS). Patients were categorized into good prognosis (GOS score >3) and poor prognosis (GOS score ≤3) groups. The relationship between NLRP3 levels and prognosis was analyzed. RESULTS: Patients with poor prognosis had significantly elevated NLRP3 levels in their serum on days 1 and 3 post-injury compared with those with a good prognosis. The difference was more pronounced during these early days compared with days 7 and 21. However, NLRP3 levels in CSF consistently showed a large difference between the two groups throughout the observation period. Receiver operating characteristic analysis revealed that the level of NLRP3 in the CSF on day 3 post-injury had the highest predictive value for prognosis, with an area under the curve of 0.83, followed by the level of NLRP3 in the serum on day 3 post-injury. CONCLUSIONS: The levels of NLRP3, especially in the CSF on day 3 post-injury, can serve as a potential biomarker for predicting prognosis in moderate to severe TBI patients. Early measurement of NLRP3 levels can provide valuable insights into patient outcomes and guide therapeutic strategies.

Evaluation of droplet deposition parameters based on the Genetic-Otsu algorithm.

Pesticide spraying is a cost-effective way to control crop pests and diseases. The effectiveness of this method relies on the deposition and distribution of the spray droplets within the targeted application area. There is a critical need for an accurate and stable detection algorithm to evaluate the liquid droplet deposition parameters on the water-sensitive paper (WSP) and reduce the impact of image noise. This study acquired 90 WSP samples with diverse coverage through field spraying experiments. The droplets on the WSP were subsequently isolated, and the coverage and density were computed, employing the fixed threshold method, the Otsu threshold method, and our Genetic-Otsu threshold method. Based on the benchmark of manually measured data, an error analysis was conducted on the accuracy of three methods, and a comprehensive evaluation was carried out. The relative error results indicate that the Genetic-Otsu method proposed in this research demonstrates superior performance in detecting droplet coverage and density. The relative errors of droplet density in the sparse, medium, and dense droplet groups are 2.7%, 1.5%, and 2.0%, respectively. The relative errors of droplet coverage are 1.5%, 0.88%, and 1.2%, respectively. These results demonstrate that the Genetic-Otsu algorithm outperforms the other two algorithms. The proposed algorithm effectively identifies small-sized droplets and accurately distinguishes the multiple independent contours of adjacent droplets even in dense droplet groups, demonstrating excellent performance. Overall, the Genetic-Otsu algorithm offered a reliable solution for detecting droplet deposition parameters on WSP, providing an efficient tool for evaluating droplet deposition parameters in UAV pesticide spraying applications.