Survival outcomes of neoadjuvant immunochemotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months. METHODS: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS). RESULTS: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar. CONCLUSION: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety.

In silico and in vivo discovery of antioxidant sea cucumber peptides with antineurodegenerative properties.

Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.

Trace amounts of palladium catalysed the Suzuki-Miyaura reaction of deactivated and hindered aryl chlorides.

Electron-rich and hindered aryl chlorides are the most challenging substrates in Suzuki-Miyaura cross-coupling (SMC) reactions. Herein, we report a highly efficient catalytic system for the SMC reaction using trace amounts of commercially available catalysts [Pd(PPh3)4/(t-Bu)PCy2; Pd loading as low as 9.5 × 10-5 mol%]. This catalytic system can efficiently couple deactivated and sterically hindered aryl chlorides with various substituted phenylboronic acids, even in one-pot multiple coupling reactions (yield of products up to 92%). The impact of solvents on SMC reactions and the mechanisms of by-product formation in aryl boronic acid couplings are analyzed using density functional theory (DFT). Utilizing trace amounts of commercially available catalysts avoids complex synthesis, reduces costs, and minimizes metal residues.

Luminescence center modulation for the synthesis of a narrow-band green phosphor: mechanism and backlighting display application.

A highly efficient and stable green phosphor with a narrow emission-band in a hexagonal aluminate was synthesized based on the energy transfer between Eu2+ and Mn2+ luminescence centers. The related mechanism was elucidated from the viewpoints of the crystal structure and energy level, providing insights for designing novel phosphors with high performance.

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant healthcare problem within both developed and developing countries, has been associated with genetic risk factors. As well, an association between physical activity and KSD risk has been hypothesized but studies have yielded inconsistent findings. This study aimed to investigate the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURES: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOMES: Individuals with KSD were identified using the International Classification of Diseases 10th Edition, and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential non-linear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared to those in the lowest quartiles: HRs (95% confidence interval) of 0.50 (0.44, 0.56), 0.57 (0.51, 0.64), and 0.66 (0.59, 0.74), respectively. TPA, MVPA, and LPA were associated with lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSION: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations.

Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis.

Background: Regulatory B cells (Bregs) play a pivotal role in suppressing immune responses, yet there is still a lack of cell surface markers that can rigorously identify them. In mouse models for multiple sclerosis (MS), TIM-1 or TIGIT expression on B cells is required for maintaining self-tolerance and regulating autoimmunity to the central nervous system. Here we investigated the activities of human memory B cells that differentially express TIM-1 and TIGIT to determine their potential regulatory function in healthy donors and patients with relapsing-remitting (RR) MS. Methods: FACS-sorted TIM-1+/-TIGIT+/- memory B (memB) cells co-cultured with allogenic CD4+ T cells were analyzed for proliferation and induction of inflammatory markers using flow cytometry and cytokine quantification, to determine Th1/Th17 cell differentiation. Transcriptional differences were assessed by SMARTSeq2 RNA sequencing analysis. Results: TIM-1-TIGIT- double negative (DN) memB cells strongly induce T cell proliferation and pro-inflammatory cytokine expression. The TIM-1+ memB cells enabled low levels of CD4+ T cell activation and gave rise to T cells that co-express IL-10 with IFNγ and IL-17A or FoxP3. T cells cultured with the TIM-1+TIGIT+ double positive (DP) memB cells exhibited reduced proliferation and IFNγ, IL-17A, TNFα, and GM-CSF expression, and exhibited strong regulation in Breg suppression assays. The functional activity suggests the DP memB cells are a bonafide Breg population. However, MS DP memB cells were less inhibitory than HC DP memB cells. A retrospective longitudinal study of anti-CD20 treated patients found that post-treatment DP memB cell frequency and absolute number were associated with response to therapy. Transcriptomic analyses indicated that the dysfunctional MS-derived DP memB/Breg population exhibited increased expression of genes associated with T cell activation and survival (CD80, ZNF10, PIK3CA), and had distinct gene expression compared to the TIGIT+ or TIM-1+ memB cells. Conclusion: These findings demonstrate that TIM-1/TIGIT expressing memory B cell subsets have distinct functionalities. Co-expression of TIM-1 and TIGIT defines a regulatory memory B cell subset that is functionally impaired in MS.

Improving product quality and productivity of an antibody-based biotherapeutic using inverted frustoconical shaking bioreactors.

The Chinese hamster ovarian (CHO) cells serve as a common choice in biopharmaceutical production, traditionally cultivated in stirred tank bioreactors (STRs). Nevertheless, the pursuit of improved protein quality and production output for commercial purposes demand exploration into new bioreactor types. In this context, inverted frustoconical shaking bioreactors (IFSB) present unique physical properties distinct from STRs. This study aims to compare the production processes of an antibody-based biotherapeutic in both bioreactor types, to enhance production flexibility. The findings indicate that, when compared to STRs, IFSB demonstrates the capability to produce an antibody-based biotherapeutic with either comparable or enhanced bioprocess performance and product quality. IFSB reduces shear damage to cells, enhances viable cell density (VCD), and improves cell state at a 5-L scale. Consequently, this leads to increased protein expression (3.70 g/L vs 2.56 g/L) and improved protein quality, as evidenced by a reduction in acidic variants from 27.0% to 21.5%. Scaling up the culture utilizing the Froude constant and superficial gas velocity ensures stable operation, effective mixing, and gas transfer. The IFSB maintains a high VCD and cell viability at both 50-L and 500-L scales. Product expression levels range from 3.0 to 3.6 g/L, accompanied by an improved acidic variants attribute of 20.6%-22.7%. The IFSB exhibits superior productivity and product quality, underscoring its potential for incorporation into the manufacturing process for antibody-based biotherapeutics. These results establish the foundation for IFSB to become a viable option in producing antibody-based biotherapeutics for clinical and manufacturing applications.

Oblique conformal anastomosis decreased the risks of cervical anastomotic leakage after totally minimally invasive esophagectomy.

OBJECTIVE: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). METHODS: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. RESULTS: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P < 0.05), which was associated with a lower incidence of cervical anastomotic leakage (X2 = 9.0260, P = 0.0027). Retrospective analysis of 539 esophageal cancer patients who underwent TMIE showed that in contrast to conventional anastomosis, oblique conformal anastomosis was an independent protective factor against cervical anastomotic leakage (P = 0.0462, OR = 0.5872, 95% CI = 0.3497-0.9993). CONCLUSION: Oblique conformation anastomosis was stronger and involved a more prominent reduced risk of cervical anastomotic leakage than conventional anastomosis after TMIE.

Prediction model of measurement errors in current transformers based on deep learning.

The long-term monitoring stability of electronic current transformers is crucial for accurately obtaining the current signal of the power grid. However, it is difficult to accurately distinguish between the fluctuation of non-stationary random signals on the primary side of the power grid and the gradual error of the transformers themselves. A current transformer error prediction model, CNN-MHA-BiLSTM, based on the golden jackal optimization (GJO) algorithm, which is used to obtain the optimal parameter values, bidirectional long short-term memory (BiLSTM) network, convolutional neural networks (CNNs), and multi-head attention (MHA), is proposed to address the difficulty of measuring error evaluation. This model can be used to determine the operation of transformers and can be widely applied to assist in determining the stability of transformer operation and early faults. First, CNN is used to mine the vertical detail features of error data at a certain moment, improving the speed of error prediction. Furthermore, a cascaded network with BiLSTM as the core is constructed to extract the horizontal historical features of the error data. The GJO algorithm is used to adjust the parameters of the BiLSTM model; optimize the hidden layer nodes, training frequency, and learning rate; and integrate MHA mechanism to promote the model to pay attention to the characteristic changes of the data in order to improve the accuracy of error prediction. Finally, this method is applied to the operation data of transformer in substations, and four time periods of data are selected to verify the model effectiveness of the current transformer dataset. The analysis results of single step and multi-step examples indicate that the proposed model has significant advantages in terms of accuracy and stability in error prediction.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Aminoazanium of A-site Cations in Metal-Free Halide Perovskite Single Crystals to Reduce Thermal Expansion for Efficient X-ray Detection.

Metal-free perovskites (MFPs) have recently become a newcomer in X-ray detection due to their flexibility and low toxicity characteristics. However, their photoelectronic properties and stability should be further improved mainly through materials design. Here, the aminoazanium of DABCO2+ was developed for the preparation of NDABCO-NH4Br3 (NDABCO = N-amino-N'-diazabicyclo[2.2.2]octonium) single crystals (SCs), and its physical properties, intermolecular interactions, and device performance were systematically explored. Notably, NDABCO-NH4Br3 can achieve improved stability by enlarging defect formation energy and inducing abundant intermolecular forces. Moreover, the slight lattice distortion could ensure the weakening electron-phonon coupling for improving carrier transport. In particular, the slight lattice distortion after the long-chain NDABCO2+ introduction could retard thermal expansion for the preparation of high-quality crystals. Finally, the corresponding X-ray detector delivered a moderate sensitivity of 623.3 µC Gyair-1 cm-2. This work provides a novel strategy through rationally designed organic cations to balance the material stability and device performance.

The association between renal pelvis urine density and the risk of severe infectious complications in patient with symptom-free hydronephrosis after shock wave lithotripsy: a multi-center prospective study.

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process.

Surface Functionalized Titanium Nitride Electrode for CMOS Compatible Bioelectronic Devices.

The development of bioelectronic devices is heading toward high throughput and high resolution. Yet, most electrode materials utilized in electrical biosensing are not compatible with the manufacturing techniques of semiconductor chips, which somehow hinders the integration and miniaturization of these devices. Titanium nitride (TiN) is a durable and economical material that is widely used in CMOS-based integrated circuits, bioelectronic systems, electrocatalytic systems, etc. Considering different application scenarios, new and efficient methods are required to functionalize TiN surface. In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salt 4-(2-hydroxyethyl)benzenediazonium was presented. Cyclic voltammetry (CV) procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i. e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical property, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characterization techniques, such as CV, atomic force microscopy (AFM), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS), etc., thereby confirming the successful grafting of hydroxyl groups onto the TiN surface. The experiments on DNA synthesis aimed to explore the potential of modified TiN electrode as a novel platform for DNA data storage applications and the corresponding proof-of-principle was accomplished by the process of coupling Cy3-phosphoramidite. Finally, the experiments were successfully reproduced on the randomly selected sites of the modified TiN microarray chips demonstrating the potential of technical protocol to extend applications in future bioelectronic devices, such as bio-sensing, high-throughput DNA synthesis, and molecular manipulation.

[Efficacy and Safety of Medical Thoracoscopic Bulla Volume Reduction in the Treatment of Chronic Obstructive Pulmonary Disease Combined With Giant Emphysematous Bullae]. / ç»å† ç§‘èƒ¸è ”é•œè‚ºå¤§ç–±å‡å®¹æœ¯æ²»ç–—æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— åˆå¹¶å·¨åž‹è‚ºå¤§ç–±çš„ç–—æ•ˆå’Œå®‰å ¨æ€§ç ”ç©¶.

Objective: To explore the efficacy and safety of medical thoracoscopic bulla volume reduction for the treatment of chronic obstructive pulmonary disease (COPD) combined with giant emphysematous bullae (GEB). Methods: A total of 66 patients with COPD combined with GEB were enrolled in the study. All the subjects received treatment at Zhengzhou Central Hospital affiliated with Zhengzhou University between March 2021 and December 2022. The subjects were divided into two groups, a medical thoracoscope group consisting of 30 cases treated with medical thoracoscopic bulla volume reduction and a surgical thoracoscope group consisting of 36 cases treated by video-assisted thoracoscopic surgery. All patients were followed up before discharge and 3 months and 6 months after discharge. The preoperative and postoperative levels of the pulmonary function, 6-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores and differences in postoperative complications were compared between the two groups. The operative duration, postoperative length-of-stay, and surgical costs and hospitalization bills, and the maximum visual analog scale (VAS) pain scores at 24 h after the procedure were assessed. Results: The baseline data of the two groups were comparable, showing no statistically significant difference. The forced expiratory volume in 1 second (FEV1) 6 months after the procedures improved in both the medical thoracoscopy group ([0.78±0.29] L vs. [1.02±0.31] L, P<0.001) and the surgical thoracoscopy group ([0.80±0.21] L vs. [1.03±0.23] L, P<0.001) compared to that before the procedures. Improvements to a certain degree in 6MWT and SGRQ scores were also observed in the two groups at 3 months and 6 months after the procedures (P<0.05). In addition, no statistically significant difference in these indexes was observed during the follow-up period of the patients in the two groups. There was no significant difference in operating time between the two groups. The medical thoracoscopy group had shorter postoperative length-of-stay ([7.3±2.6] d) and 24-hour postoperative VAS pain scores (3.0 [2.0, 3.3]) than the surgical thoracoscopic group did ([10.4±4.3] d and 4.5 [3.0, 5.0], respectively), with the differences being statistically significant (P<0.05). Surgical cost and total hospitalization bills were lower in the medical thoracoscopy group than those in the surgical thoracoscopy group (P<0.05). The complication rate in the medical thoracoscopy group was lower than that in the surgical thoracoscopy group (46.7% vs. 52.8%), but the difference was not statistically significant. Conclusion: Medical thoracoscopic reduction of bulla volume can significantly improve the pulmonary function, quality of life, and exercise tolerance of patients with COPD combined with GEB, and it can reduce postoperative short-term pain and shorten postoperative length-of-stay. The procedure has the advantages of minimal invasiveness, quick recovery, and low costs. Hence extensive clinical application is warranted.

Ultrahigh-Performance Fiber-Supported Iron-Based Ionic Liquid for Synthesizing 3,4-Dihydropyrimidin-2-(1H)-ones in a Cleaner Manner.

Herein, a fiber-supported iron-based ionic liquid as a type of fibrous catalyst has been developed for the synthesis of bioactive 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) via three-component Biginelli reactions in a cleaner manner. The described fibrous catalyst was obtained from the commercially available polyetheretherketone (PEEK) fiber by postfunctionalization processes and was characterized and analyzed in detail by means of diversified technologies. Furthermore, the fiber-supported iron-based ionic liquids could mediate the classical three-component Biginelli reactions to proceed smoothly to gain a variety of substituted DHPMs with yields of up to 99%. The superior catalytic activities of the fibrous catalyst were ascribed to the quasi-homogeneous medium by ionic liquids generated in the surface layer of the PEEK fiber, which could afford an appropriate reaction zone and could further be available for the aggregation of substrates to facilitate the three-component reaction. Notably, the fibrous catalyst is available for recycling over 10 runs just by a pair of tweezers, and the operational procedure was capable of enlarging the catalytic system to the gram-scale without any performance degradation, which provided a cleaner manner to take advantage of the iron-based catalyst in organic synthesis with potential industrialization prospects.

Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children.

Biallelic mutation in the DNA-damage repair gene NBN is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline NBN variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline NBN variants and identified 25 unique, putatively damaging NBN coding variants in 50 patients. Compared with the frequency of NBN variants in gnomAD non-cancer controls (189 unique, putatively damaging NBN coding variants in 472 of 118,479 individuals) we found significant overrepresentation in pediatric B-ALL (p=0.004, OR=1.8). Most B-ALL-risk variants were missense and cluster within the NBN N-terminal domains. Using two functional assays, we verified 14 of 25 variants with severe loss-of-function phenotypes and thus classified these as non-functional or partially functional. Finally, we found that germline NBN variant carriers, all of which were identified as heterozygous genotypes, showed similar survival outcomes relative to those with WT status. Taken together, our findings provide novel insights into the genetic predisposition to B-ALL, and the impact of NBN variants on protein function and suggest that heterozygous NBN variant carriers may safely receive B-ALL therapy.

High-throughput DNA synthesis for data storage.

With the explosion of digital world, the dramatically increasing data volume is expected to reach 175 ZB (1 ZB = 1012 GB) in 2025. Storing such huge global data would consume tons of resources. Fortunately, it has been found that the deoxyribonucleic acid (DNA) molecule is the most compact and durable information storage medium in the world so far. Its high coding density and long-term preservation properties make itself one of the best data storage carriers for the future. High-throughput DNA synthesis is a key technology for "DNA data storage", which encodes binary data stream (0/1) into quaternary long DNA sequences consisting of four bases (A/G/C/T). In this review, the workflow of DNA data storage and the basic methods of artificial DNA synthesis technology are outlined first. Then, the technical characteristics of different synthesis methods and the state-of-the-art of representative commercial companies, with a primary focus on silicon chip microarray-based synthesis and novel enzymatic DNA synthesis are presented. Finally, the recent status of DNA storage and new opportunities for future development in the field of high-throughput, large-scale DNA synthesis technology are summarized.

Photothermal Mineralization of Polyolefin Microplastics via TiO2 Hierarchical Porous Layer-Based Semiwetting Air-Plastic-Solid Interfaces.

Photo-mineralization of microplastics under mild conditions has emerged as a promising solution to plastic waste disposal. However, the inadequate contact between oxygen, water-insoluble polyolefin microplastics, and photocatalysts remains a critical issue. In this study, a TiO2 hierarchical porous layer (TiO2-HPL) photocatalyst is presented to establish air-plastic-solid triphase interfaces for the photothermal mineralization of polyolefins. The wettability of the TiO2-HPL-based triphase interface is finely controlled from plastophobic to plastophilic. High-resolution imaging and finite element simulation demonstrate the significance of a semiwetting state in achieving multidirectional oxygen diffusion through the hierarchical pore structure while maintaining sufficient contact between the plastic phase and photocatalysts. For low-density polyethylene, the TiO2-HPL achieves a photothermal mineralization rate of 5.63 mmol g-1 h-1 and a conversion of 26.3% after 20 h of continuous irradiation. Additionally, the triphase photocatalytic system with semiwetting gas-plastic-solid interfaces shows good universality for various polyolefin reagents and products, illustrating its potential in achieving efficient photothermal mineralization of non-degradable microplastics.