Anaerobic dynamic membrane bioreactor treating sulfamethoxazole wastewater: advantages of dynamic membrane and its fouling mechanism.

Discharge of improperly treated sulfamethoxazole (SMX) wastewater seriously threats environmental security and public health. Anaerobic dynamic membrane bioreactors (AnDMBRs) technology would be cost-effective for SMX wastewater treatment, considering its low cost and satisfactory treatment efficiency. The performance of AnDMBR, though demonstrated to be excellent in treating many types of wastewaters, was for the first time investigated for treating SMX wastewater. Particular efforts were devoted to elucidating the advantages of dynamic membrane (DM) and the governing mechanism responsible for DM fouling with the presence of SMX. The threshold SMX concentration for AnDMBR was found to be 90 mg/L and the AnDMBR exhibited excellent removal efficiency of COD (90.91 %) and SMX (88.95 %) as well as satisfactory acute toxicity reduction rate (88.84 %). It was noteworthy that the DM made indispensable contributions to the removal of COD (14.26 %) and SMX (22.20 %) as well as the acute reduction of toxicity (25.81 %). The presence of SMX significantly accelerated DM fouling mainly by increasing its specific resistance, which was attributed to the increased content of small particles, high-valence metal ions and EPS content (mainly hydrophobic proteins), resulting in a denser DM structure with lower porosity. Besides, the biofouling-related bacteria (Firmicutes) was found to be enriched in the DM with the presence of SMX.

Altered structural node of default mode network mediated general cognitive ability in young adults with obesity.

BACKGROUND: Obesity, characterized by excessive adiposity, is associated with brain structural abnormalities. Nevertheless, the relationships between altered structural nodes of default mode network (DMN), body mass index (BMI), general cognitive ability remained unclear in young adults. METHODS: In this study, we divided a large sample of young adults into three BMI-based groups. We then conducted one-way analyses of variance and post-hoc tests with Bonferroni corrections to investigate abnormal structural brain regions associated with obesity. Furthermore, mediation effects models were built to explore whether the structural alterations influenced the relationship between BMI and general cognitive ability. RESULTS: Compared to their lean and overweight counterparts, young adults with obesity exhibited significantly lower general cognitive ability, higher impulsivity traits, and worse sleep quality. Furthermore, compared with lean group, young adults with obesity exhibited altered cortical thickness of both the left temporal pole and right superior parietal lobule, and abnormal cortical surface area (CSA) of the left entorhinal cortex (EC), a hub within DMN. Moreover, CSA of the left EC mediated the relationship between BMI and general cognitive ability. CONCLUSION: Obesity was linked to altered structural node of DMN, which mediated general cognitive ability in young adults. These findings indicated the negative effect of obesity on DMN and general cognitive ability in young adults.

Identification and Functional Analysis of E3 Ubiquitin Ligase g2e3 in Chinese Tongue Sole, Cynoglossus semilaevis.

Gametogenesis, the intricate developmental process responsible for the generation of germ cells (gametes), serves as a fundamental prerequisite for the perpetuation of the reproductive cycle across diverse organisms. The g2e3 enzyme is a putative ubiquitin E3 ligase implicated in the intricate regulatory mechanisms underlying cellular proliferation and division processes. The present study delves into the function of G2/M phase-specific E3 ubiquitin protein ligase (Cs-g2e3) in gametogenesis in Chinese Tongue Sole (Cynoglossus semilaevis). Sequence analysis shows that the Cs-g2e3 mRNA spans 6479 bp, encoding a 733 amino acid protein characterized by three conserved structural domains: PHD, RING, and HECT-typical of HECT E3 ubiquitin ligases. The predominant expression of Cs-g2e3 in the gonad tissues is further verified by qPCR. The expression profile of Cs-g2e3 in the gonads of the Chinese Tongue Sole is analyzed at different ages, and the results show that its expression peaks at 8 months of age and then begins to decline and stabilize. It is noteworthy that the expression level remains significantly elevated compared to that observed during the juvenile period. In situ hybridization shows that the mRNA of Cs-g2e3 is mainly localized in the germ cells of the ovary and the testis. RNA interference experiments show that the knockdown of Cs-g2e3 in ovarian and testicular germ cell lines significantly downregulates the expression of key genes involved in oogenesis (e.g., sox9 and cyp19a) and spermatogenesis (e.g., tesk1 and piwil2), respectively. Furthermore, the analysis of mutations in the transcription factor binding sites reveals that mutations within the Myogenin, YY1, and JunB binding sites significantly impact the transcriptional activity of the Cs-g2e3 gene, with the mutation in the YY1 binding site exhibiting the most pronounced effect (p < 0.001). This study contributes to a deeper understanding of the tissue-specific expression patterns of Cs-g2e3 across various tissues in Cynoglossus semilaevis, as well as the potential regulatory influences of transcription factors on its promoter activity. These findings may facilitate future research endeavors aimed at elucidating the expression and functional roles of the Cs-g2e3 gene.

Hexagonal Mg2B2 and Ca2B2 monolayers as promising anode materials for Li-ion and Na-ion batteries.

Exploring new high-performance anode materials is of great significance for next generation renewable energy technologies. Two-dimensional (2D) transition metal borides, named as MBenes, are receiving increasing attention in energy storage fields due to their structure-and-composition diversities and high electrical conductivities. Expanding the family of hexagonal MBenes to non-transition metal borides, we report two hexagonal IIA metal M2B2-typed MBenes and demonstrate the feasibility of exfoliation and application as anode materials for Li-ion batteries (LIBs) and Na-ion batteries (SIBs) using ab initio calculations. The predicted 2D Mg2B2 and Ca2B2 monolayers exhibit robust thermal and mechanical stabilities, inherent metallic properties, electrical conductivities, and excellent electrode performance. The outstanding theoretical specific capacities of Mg2B2 and Ca2B2 for Li/Na ions reach up to 764/527 and 859/527 mA h g-1, respectively. Furthermore, the average open-circuit voltages (OCVs) of Mg2B2 and Ca2B2 range from 0.275 to 0.395 V, indicating their suitability for anode materials. Additionally, the low diffusion energy barriers of Mg2B2 and Ca2B2 for Li/Na ions at delithiated/desodiated states (27/14 and 16/12 meV) and lithiated/sodiated states (187/58 and 52/34 meV) illustrate their excellent charge-discharge capabilities. These intriguing findings demonstrate the superior performance of the predicted IIA metal boride monolayers as promising anode materials for LIBs and SIBs and break through the limitations of transition metal MBenes as anode materials in terms of overall performance. Our study opens the door to the application of the main group metal MBenes in ion energy storage.

Pivotal Role of Modifiable A-Site Doping in Enhancing Valence Stability and Excited State Dynamics of MnO6.

The controlled regulation of A-site in rare earth manganate perovskites can orderly arrange the electronic states, leading to the emergence of unique transport properties. However, it is challenging to balance crystal structure stability and property variations during the multi-ion doping. In this study, a series of multivalent manganate perovskites are synthesized by hydrothermal method through the A-site multielement doping, which enables the manganese atoms with varying valence states to orderly arrange at the B site. Powder X-ray diffraction (PXRD) and X-ray absorption spectra (XAS) confirm that the splitting of the K─O hybrid orbitals in the crystal effectively prevents any distortion of the MnO6 octahedron, thereby facilitating the ordered arrangement of Mn (III) -Mn (IV) -Mn (V) at the B-site and promoting superstructure formation. The transient absorption spectra (TAS) reveals that the sequential arrangement of Mn (III) - Mn (IV) - Mn(V) better forms the charge transfer channels, and thereby makes the photodynamic properties of the sample composition-dependent. These photodynamic properties will facilitate the study of exciton-electron coupling behavior in LCKMO crystals during electrical transport.

Current state of research on acupuncture for the treatment of post-stroke dysphagia: a scoping review.

Objective: Post-stroke dysphagia (PSD) is a common complication of stroke. Acupuncture as one of the traditional therapies in traditional Chinese medicine (TCM), can change the excitability of cerebral cortical nerve cells, and promote the recovery of neurological and swallowing functions. Several clinical primary studies (including RCTs, cohort studies, etc.) and systematic reviews have demonstrated its efficacy and safety in patients with PSD. The positive effects of acupuncture on PSD are also mentioned in international clinical and treatment guidelines, while there is no synthesis of this evidence. This scoping review aims to summarize the evidence from clinical primary studies, reviews, systematic reviews, and guidelines on acupuncture for the treatment of PSD and explore the breadth of this evidence, provide an overview of the range and characteristics of existing evidence, research gaps, and future research priorities in treating PSD with acupuncture. Method: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, SinoMed, Wan Fang Data, and VIP databases were searched from inception until June 12, 2024. The relevant data were presented through bubble diagrams, line graphs, and structured tables along with descriptive statistics and analysis. This scoping review was conducted based on the PRISMA-ScR Checklist. Results: A total of 1,130 studies were included. Most of the studies were conducted in China, with the number increasing over time. The studies included 254 reviews, 815 clinical studies (678 RCTs,107 nRCTs, 12 case reports, 14 cohort studies, and four case series), 51 systematic reviews, and 10 guidelines. Acupuncture interventions included manual acupuncture (MA), electroacupuncture (EA), and MA/EA combined with acupuncture-related methods (such as scalp acupuncture, auricular acupuncture, warm acupuncture, etc.). The most frequently used acupoint was RN23. Acupuncture is often applied in combination with other treatments, such as herbal medicine, Western medicine, rehabilitation training, swallowing training, or catheter balloon dilatation. Effective rates and WTS were the most frequently used outcomes. Most studies reported significant efficacy and only a few studies explicitly reported adverse events. Acupuncture received positive recommendations in nine guidelines for the treatment of PSD. Conclusion: As a convenient and safe traditional Chinese medicine therapy with its characteristics, acupuncture can improve different stages and types of dysphagia without causing serious adverse reactions. In the future, more standardized international cooperative clinical research is needed to identify the influence of different acupuncture intervention times on the curative effect and dose-effect relationship of acupuncture; standardize the clinical acupoint selection scheme of acupuncture; develop a COS with TCM characteristics to improve the quality of outcome reporting, This will enable different research data to be summarized and compared, reduce resource waste, and provide more high-quality evidence.

Strong angular and spectral narrowing of electroluminescence in an integrated Tamm-plasmon-driven halide perovskite LED.

Next-generation light-emitting applications such as displays and optical communications require judicious control over emitted light, including intensity and angular dispersion. To date, this remains a challenge as conventional methods require cumbersome optics. Here, we report highly directional and enhanced electroluminescence from a solution-processed quasi-2-dimensional halide perovskite light-emitting diode by building a device architecture to exploit hybrid plasmonic-photonic Tamm plasmon modes. By exploiting the processing and bandgap tunability of the halide perovskite device layers, we construct the device stack to optimise both optical and charge-injection properties, leading to narrow forward electroluminescence with an angular full-width half-maximum of 36.6° compared with the conventional isotropic control device of 143.9°, and narrow electroluminescence spectral full-width half-maximum of 12.1 nm. The device design is versatile and tunable to work with emission lines covering the visible spectrum with desired directionality, thus providing a promising route to modular, inexpensive, and directional operating light-emitting devices.

High-resolution, broad-spectral-range Raman measurement using a spatial heterodyne spectrometer with separate filters and multi-gratings.

We propose a high-resolution, broad-spectral-range spatial heterodyne Raman spectrometer (SHRS) having separate filters and multi-gratings (SFMG). A prototype of the SFMG-SHRS is built using multi-gratings with four sub-gratings having groove densities of 320, 298, 276, and 254 gr/mm and separate filters with filter bands corresponding to the sub-gratings. We use the SFMG-SHRS to measure the Raman spectra of inorganic and organic compounds with various integration times, laser power, and transparent containers, compare measurements of microplastics with and without the separate filters, and measure mixtures of inorganic powders and organic solutions. The designed SFMG-SHRS makes high-resolution, broad-spectral-range Raman measurements with improved signal-to-noise ratios and visibility of weak Raman peaks even in the presence of fluorescence.

Development of a high-resolution, broadband spatial heterodyne Raman spectrometer based on field-widened grating-echelle structure.

We propose a spatial heterodyne Raman spectrometer (SHRS) based on a field-widened grating-echelle (FWGE). A normal grating is combined with an echelle grating in a conventional spatial heterodyne spectrometer to eliminate ghost images without using masks, and prevents interference among the spatial frequencies of different diffraction orders. Mathematical expressions and derivation processes are given for the spectral parameters in the FWGE-SHRS and a verification breadboard system is fabricated. The FWGE-SHRS measures Raman spectra of single chemicals and mixed targets with different integration times, laser powers, concentrations, and transparent containers. The results of the experiments demonstrate that the FWGE-SHRS is suitable for high-resolution, broadband Raman measurements for a wide range of applications.

Fabrication of red-emitting perovskite LEDs by stabilizing their octahedral structure.

Light-emitting diodes (LEDs) based on metal halide perovskites (PeLEDs) with high colour quality and facile solution processing are promising candidates for full-colour and high-definition displays1-4. Despite the great success achieved in green PeLEDs with lead bromide perovskites5, it is still challenging to realize pure-red (620-650 nm) LEDs using iodine-based counterparts, as they are constrained by the low intrinsic bandgap6. Here we report efficient and colour-stable PeLEDs across the entire pure-red region, with a peak external quantum efficiency reaching 28.7% at 638 nm, enabled by incorporating a double-end anchored ligand molecule into pure-iodine perovskites. We demonstrate that a key function of the organic intercalating cation is to stabilize the lead iodine octahedron through coordination with exposed lead ions and enhanced hydrogen bonding with iodine. The molecule synergistically facilitates spectral modulation, promotes charge transfer between perovskite quantum wells and reduces iodine migration under electrical bias. We realize continuously tunable emission wavelengths for iodine-based perovskite films with suppressed energy loss due to the decrease in bond energy of lead iodine in ionic perovskites as the bandgap increases. Importantly, the resultant devices show outstanding spectral stability and a half-lifetime of more than 7,600 min at an initial luminance of 100 cd m-2.

Chromatin modifier Hmga2 promotes adult hematopoietic stem cell function and blood regeneration in stress conditions.

The molecular mechanisms governing the response of hematopoietic stem cells (HSCs) to stress insults remain poorly defined. Here, we investigated effects of conditional knock-out or overexpression of Hmga2 (High mobility group AT-hook 2), a transcriptional activator of stem cell genes in fetal HSCs. While Hmga2 overexpression did not affect adult hematopoiesis under homeostasis, it accelerated HSC expansion in response to injection with 5-fluorouracil (5-FU) or in vitro treatment with TNF-α. In contrast, HSC and megakaryocyte progenitor cell numbers were decreased in Hmga2 KO animals. Transcription of inflammatory genes was repressed in Hmga2-overexpressing mice injected with 5-FU, and Hmga2 bound to distinct regions and chromatin accessibility was decreased in HSCs upon stress. Mechanistically, we found that casein kinase 2 (CK2) phosphorylates the Hmga2 acidic domain, promoting its access and binding to chromatin, transcription of anti-inflammatory target genes, and the expansion of HSCs under stress conditions. Notably, the identified stress-regulated Hmga2 gene signature is activated in hematopoietic stem progenitor cells of human myelodysplastic syndrome patients. In sum, these results reveal a TNF-α/CK2/phospho-Hmga2 axis controlling adult stress hematopoiesis.

Tactile discrimination as a diagnostic indicator of cognitive decline in patients with mild cognitive impairment: A narrative review.

Background: Tactile discrimination, a cognitive task reliant on fingertip touch for stimulus discrimination, encompasses the somatosensory system and working memory, with its acuity diminishing with advancing age. Presently, the evaluation of cognitive capacity to differentiate between individuals with early Alzheimer's disease (AD) and typical older adults predominantly relies on visual or auditory tasks, yet the efficacy of discrimination remains constrained. Aims: To review the existing tactile cognitive tasks and explore the interaction between tactile perception and the pathological process of Alzheimer's disease. The tactile discrimination task may be used as a reference index of cognitive decline in patients with mild cognitive impairment and provide a new method for clinical evaluation. Methods: We searched four databases (Embase, PubMed, Web of Science and Google scholar). The reference coverage was from 1936 to 2023. The search terms included "Alzheimer disease" "mild cognitive impairment" "tactile" "tactile discrimination" "tactile test" and so on. Reviews and experimental reports in the field were examined and the effectiveness of different types of tactile tasks was compared. Main results: Individuals in the initial phases of Alzheimer's spectrum disease, specifically those in the stage of mild cognitive impairment (MCI), exhibit notable impairments in tasks involving tactile discrimination. These tasks possess certain merits, such as their quick and straightforward comparability, independence from educational background, and ability to circumvent the limitations associated with conventional cognitive assessment scales. Furthermore, tactile discrimination tasks offer enhanced accuracy compared to cognitive tasks that employ visual or auditory stimuli. Conclusions: Tactile discrimination has the potential to serve as an innovative reference indicator for the swift diagnosis of clinical MCI patients, thereby assisting in the screening process on a clinical scale.

Exogenous Melatonin Enhances Dihydrochalcone Accumulation in Lithocarpus litseifolius Leaves via Regulating Hormonal Crosstalk and Transcriptional Profiling.

Dihydrochalcones (DHCs) constitute a specific class of flavonoids widely known for their various health-related advantages. Melatonin (MLT) has received attention worldwide as a master regulator in plants, but its roles in DHC accumulation remain unclear. Herein, the elicitation impacts of MLT on DHC biosynthesis were examined in Lithocarpus litseifolius, a valuable medicinal plant famous for its sweet flavor and anti-diabetes effect. Compared to the control, the foliar application of MLT significantly increased total flavonoid and DHC (phlorizin, trilobatin, and phloretin) levels in L. litseifolius leaves, especially when 100 µM MLT was utilized for 14 days. Moreover, antioxidant enzyme activities were boosted after MLT treatments, resulting in a decrease in the levels of intracellular reactive oxygen species. Remarkably, MLT triggered the biosynthesis of numerous phytohormones linked to secondary metabolism (salicylic acid, methyl jasmonic acid (MeJA), and ethylene), while reducing free JA contents in L. litseifolius. Additionally, the flavonoid biosynthetic enzyme activities were enhanced by the MLT in leaves. Multiple differentially expressed genes (DEGs) in RNA-seq might play a crucial role in MLT-elicited pathways, particularly those associated with the antioxidant system (SOD, CAT, and POD), transcription factor regulation (MYBs and bHLHs), and DHC metabolism (4CL, C4H, UGT71K1, and UGT88A1). As a result, MLT enhanced DHC accumulation in L. litseifolius leaves, primarily by modulating the antioxidant activity and co-regulating the physiological, hormonal, and transcriptional pathways of DHC metabolism.

The effect of histo-blood group ABO system transferase (BGAT) on pregnancy related outcomes：A Mendelian randomization study.

Protein level of Histo-Blood Group ABO System Transferase (BGAT) has been reported to be associated with cardiometabolic diseases. But its effect on pregnancy related outcomes still remains unclear. Here we conducted a two-sample Mendelian randomization (MR) study to ascertain the putative causal roles of protein levels of BGAT in pregnancy related outcomes. Cis-acting protein quantitative trait loci (pQTLs) robustly associated with protein level of BGAT (P < 5 ×10-8) were used as instruments to proxy the BGAT protein level (N = 35,559, data from deCODE), with two additional pQTL datasets from Fenland (N = 10,708) and INTERVAL (N = 3301) used as validation exposures. Ten pregnancy related diseases and complications were selected as outcomes. We observed that a higher protein level of BGAT showed a putative causal effect on venous complications and haemorrhoids in pregnancy (VH) (odds ratio [OR]=1.19, 95% confidence interval [95% CI]=1.12-1.27, colocalization probability=91%), which was validated by using pQTLs from Fenland and INTERVAL. The Mendelian randomization results further showed effects of the BGAT protein on gestational hypertension (GH) (OR=0.97, 95% CI=0.96-0.99), despite little colocalization evidence to support it. Sensitivity analyses, including proteome-wide Mendelian randomization of the cis-acting BGAT pQTLs, showed little evidence of horizontal pleiotropy. Correctively, our study prioritised BGAT as a putative causal protein for venous complications and haemorrhoids in pregnancy. Future epidemiology and clinical studies are needed to investigate whether BGAT can be considered as a drug target to prevent adverse pregnancy outcomes.

Excited-State Engineering Enables Efficient Deep-Blue Light-Emitting Diodes Exhibiting BT.2020 Color Gamut.

Organic luminescent materials that exhibit thermally activated delayed fluorescence (TADF) can convert non-emissive triplet excitons into emissive singlet states through a reverse intersystem crossing (RISC) process. Therefore, they have tremendous potential for applications in organic light-emitting diodes (OLEDs). However, with the development of ultra-high definition 4K/8K display technologies, designing efficient deep-blue TADF materials to achieve the Commission Internationale de l'Éclairage (CIE) coordinates fulfilling BT.2020 remains a significant challenge. Here, an effective approach is proposed to design deep-blue TADF molecules based on hybrid long- and short-range charge-transfer by incorporation of multiple donor moieties into organoboron multiple resonance acceptors. The resulting TADF molecule exhibits deep-blue emission at 414 nm with a full width at half maximum (FWHM) of 29 nm, together with a thousand-fold increase in RISC rate. OLEDs based on the champion material achieve a record maximum external quantum efficiency (EQE) of 22.8% with CIE coordinates of (0.163, 0.046), approaching the coordinates of the BT.2020 blue standard. Moreover, TADF-assisted fluorescence devices employing the designed material as a sensitizer exhibit an exceptional EQE of 33.1%. This work thus provides a blueprint for future development of efficient deep-blue TADF emitters, representing an important milestone towards meeting the blue color gamut standard of BT.2020.

The relationship between family cohesion and bedtime procrastination among Chinese college students: the chain mediating effect of coping styles and mobile phone addiction.

BACKGROUND: Bedtime procrastination refers to an individual's inability to go to bed at a predetermined time without external obstacles. Previous researchers have found that the bedtime procrastination is harmful to human physical and mental health, but these research on bedtime procrastination have mostly focused on exploring individual factors, while ignoring the external environmental factors. Therefore, this is the first study to investigate bedtime procrastination from the perspective of family environments. METHODS: The study was conducted using a convenient sampling method and online questionnaires. Family Cohesion Scale, Coping Styles Questionnaire, Mobile Phone Addiction Tendency Scale and Bedtime Procrastination Scale were used to measure sleep and psychological condition of 1,048 college students. RESULTS: Family cohesion negatively predicted bedtime procrastination. Additionally, positive coping style and mobile phone addiction had significant independent mediating effects. Furthermore, positive coping style and mobile phone addiction had chain mediating effects between family cohesion and bedtime procrastination. CONCLUSION: This study revealed the effect of coping styles and mobile phone addiction on the relationship between family cohesion and bedtime procrastination among Chinese college students. These findings explained the mechanisms of bedtime procrastination from the perspective of environment, so as to effectively intervene the bedtime procrastination of college students from the perspective of external environment.

Effect of preoperative immunonutrition on postoperative short-term clinical outcomes in patients with gastric cancer cachexia: a prospective randomized controlled trial.

BACKGROUND: Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. PATIENTS AND METHODS: 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. RESULTS: The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). CONCLUSION: Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients' inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

Reactive cutaneous capillary endothelial proliferation following camrelizumab monotherapy or combination therapy for multi-cancers: a large-scale pooled analysis of 10 studies in China.

Background: Skin toxicities are the most common adverse events related to immunotherapy, such as reactive cutaneous capillary endothelial proliferation (RCCEP) following treatment with the anti-programmed cell death-1 antibody camrelizumab. Objective: This study aimed to comprehensively analyze the clinical features and prognostic value of RCCEP in patients with malignancies who received camrelizumab alone (Camre) or in combination with the angiogenesis-targeted agent apatinib (Camre-Apa) or chemotherapy (Camre-Chemo). Design: A large-scale pooled analysis. Methods: Individual patient-level data were derived from 10 clinical trials of camrelizumab monotherapy, camrelizumab plus apatinib, or camrelizumab plus chemotherapy (n = 1305). Results: RCCEP occurred in 77.0% (516/670) of patients with Camre, 23.6% (70/296) with Camre-Apa, and 67.8% (230/339) with Camre-Chemo. Most RCCEP lesions were grade 1 or 2 in severity. The median time to onset was 0.8 months [interquartile range (IQR), 0.6-1.2] with Camre, 5.0 months (IQR, 2.7-8.0) with Camre-Apa, and 1.6 months (IQR, 1.0-4.2) with Camre-Chemo; and the median duration was 4.8 months (IQR, 2.6-8.8), 4.4 months (IQR, 1.7-8.9), and 7.2 months (IQR, 4.1-14.3), respectively. In all the three groups, patients with RCCEP showed significantly better clinical outcomes compared with those without [objective response rate: 23.8% versus 1.9% with Camre, 48.6% versus 21.2% with Camre-Apa, and 78.7% versus 54.1% with Camre-Chemo; median progression-free survival: 3.2 versus 1.7 months (hazard ratio (HR) = 0.36), 10.2 versus 4.5 months (HR = 0.39), and 12.7 versus 7.3 months (HR = 0.38); median overall survival: 13.3 versus 3.8 months (HR = 0.34), 29.2 versus 13.5 months (HR = 0.46), and not reached versus 12.8 months (HR = 0.19); all p < 0.0001]. Conclusion: Although RCCEP occurred frequently with camrelizumab, most lesions were mild and self-limiting. The occurrence of RCCEP was strongly associated with the antitumor activity and survival of camrelizumab, both as monotherapy and in combination therapy.

Validation of numerical simulations and experiments on impulse characteristics induced by self-excited oscillation.

The high-frequency pulse flow, equivalent to the natural frequency of rocks, is generated by a self-excited oscillating cavity to achieve resonance rock-breaking. The flow field and oscillating mechanism of the self-excited oscillating cavity were simulated using the large eddy simulation method of Computational Fluid Dynamics (CFD). A field-scale testing apparatus was developed to investigate the impulse characteristics and verify the simulation results. The results show that the fluid at the outlet at the tool is deflected due to the pulse oscillation of the fluid. The size and shape of low-pressure vortices constantly change, leading to periodic changes in fluid impedance within the oscillating cavity. The impulse frequency reaches its highest point when the length-diameter ratio is 0.67. As the length-diameter ratio increases, the tool pressure loss also increases. Regarding the cavity thickness, the impulse frequency of the oscillating cavity initially decreases, then increases, and finally decreases again. Moreover, both the impulse frequency and pressure loss increase with an increase in displacement. The numerical simulation findings align with the experimental results, thus confirming the validity of the theoretical model. This research provides theoretical guidance for the practical application of resonance rock-breaking technology.