Construction of an ideotype root system architecture of subsurface flow constructed wetland macrophytes by vertical spatial stress: strengthening of rhizosphere effects and determination of appropriate substrate depth.

Strengthening rhizosphere effects to enhance pollutant removal is a hotspot of constructed wetlands (CWs) research in recent years, and improving the root traits and metabolic capacity of macrophytes is crucial for strengthening rhizosphere effects. In the field experiment, two types of subsurface flow (SSF) CWs (CW10 and CW20, with substrate depths of 10 and 20 cm, respectively) under the vertical spatial stress of roots (VSSR) and two types of non-VSSR SSF CWs (CW40 and CW60) were adopted with Typha orientalis as cultivated plants to investigate the variability of root development, metabolism, and pollutant removal at different substrate depths. VSSR induced substantial redundant root development, which significantly increased root-shoot ratio, fine and lateral root biomass, root porosity, and root activity, with lateral and fine root biomass of CW20 reaching 409.17 and 237.42 g/m2, respectively, which were 3.18 and 5.28 times those of CW60. The radical oxygen loss (ROL) and dissolved organic carbon (DOC) levels of CW20 single plant were 1.36 and 4.57 times higher than those of CW60, respectively, and more types of root exudates were determined (e.g., aldehydes, ketones and amides). More aerobic heterotrophs (e.g., Massilia, Planomicrobium), nitrification bacteria (e.g., Ellin6067, Nitrospira), aerobic denitrification bacteria (e.g., Bacillu, Chryseobacterium, Pseudomonas) and denitrification phosphorus accumulating organisms (e.g., Flavobacterium) were enriched in the rhizosphere of CW20. This changed the main transformation pathways of pollutants and enhanced the removal of pollutants, with the COD, TN and TP average removal rates of CW20 increasing by 9.99%, 13.28% and 8.92%, respectively, compared with CW60. The ideotype root system architecture CW (RSACW; CW20) constructed in this study, which consists of a large number of fine and lateral roots, can stimulate more efficient rhizosphere effects stably and continuously.

Binding Analysis of Sf-SR-C MAM Domain and Sf-FGFR Ectodomain to Vip3Aa.

Bacillus thuringiensis Vip3Aa has been widely used in transgenic crops to resist the erosion of insects. The Scavenger Receptor-C (SR-C) and Fibroblast Growth Factor Receptor (FGFR) of Spodoptera frugiperda (Sf-SR-C and Sf-FGFR) have formerly been identified as the cell receptors of Vip3Aa. However, the interaction mechanism of Vip3Aa binding to Sf-SR-C or Sf-FGFR is still unknown. Here, we purified the MAM domain of Sf-SR-C (Sf-MAM) and the Sf-FGFR ectodomain expressed extracellularly by Sf9 cells. We then solved the crystal structure of the Sf-MAM domain. Structure docking analysis of the Sf-MAM and Vip3Aa C-terminal domain (CTD) excluded the possibility of the two proteins binding. A further surface plasmon resonance (SPR) assay also revealed that the Sf-MAM and Sf-FGFR ectodomain could not bind to the Vip3Aa protein. Our results have raised the urgency of determining the authentic cell receptor for Vip3Aa.

Effect of interactions between humic acid and cerium oxide nanoparticles on the toxicity to the Chlorella sp.

With the wide application of nanomaterials, the concentration of nanomaterials in natural water continues to increase, which poses a severe threat to the water environment. However, the influence of organic matter and nanomaterials rich in natural water on the toxic effect of algae growth is still unclear. In this study, the effects of humic acid (HA) and nano-cerium oxide (nCeO2) on the physiology and transcriptome of Chlorella sp. were analyzed, and the mechanism of the toxic effect of HA on Chlorella sp. under nCeO2 stress was revealed. Under 20-200 mg/L nCeO2 stress, the growth of Chlorella cells was inhibited and the highest inhibition rate reached 52% within 200 mg/L nCeO2. The Fv/Fm and ETRmax values of Chlorella sp. decreased from 0.490 and 24.45 (20 mg/L nCeO2) to 0.488 and 23.4 (100 mg/L nCeO2), respectively. Under the stimulation of nCeO2, the level of reactive oxygen species in algal cells was increased, accompanied by lipid peroxidation and membrane damage. However, the addition of HA at concentrations of 5-10 mg/L effectively alleviated the toxic effect of nCeO2 on Chlorella sp. Transcriptome analysis showed that 10 mg/L HA could alleviate the cellular stress at 100 mg/L nCeO2 on Chlorella sp. by regulating genes related to photosynthesis and metabolism pathways. Moreover, the downregulation of genes (e.g., Lhca1, Lhcb1, AOC3, and AOC2) indicated that HA reduced the level of oxidative stress in Chlorella sp. These findings offer novel insights of evaluating the ecotoxicity nCeO2 and HA in natural water environment and their impact on Chlorella sp.

Structural insights into the Langya virus attachment glycoprotein.

Langya virus (LayV) was recently detected in patients with acute pneumonic diseases in China. Genome alignment indicated that LayV is a type of zoonotic henipavirus (HNV) that might also infect domestic animals. Previous studies revealed that HNVs mainly use ephrin-B1, ephrin-B2, or ephrin-B3 as cell receptors and the attachment glycoprotein (G) is the host cell receptor-binding protein. However, the LayV receptor remains unknown. Here, we present the 2.77 Å crystal structure of the LayV G C-terminal domain (CTD). We show that the LayV G protein CTD possesses a similar architecture as the Mojiang virus (MojV) G protein but is markedly different from the Nipah virus (NiV), Hendra virus (HeV), and Cedar virus (CedV) G proteins. Surface plasmon resonance (SPR) experiments indicate that LayV G does not bind ephrin-B proteins. Steric hindrance may prevent interactions between LayV G and ephrin-B. Our data might facilitate drug development targeting LayV.

Different machine learning methods based on maxillary sinus in sex estimation for northwestern Chinese Han population.

BACKGROUND & OBJECTIVE: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements. MATERIAL & METHODS: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt. RESULTS: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age. CONCLUSION: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

[Establishment and Optimization of Quality Standards for the Traditional Tibetan Medicine Preparation of Liuwei Nengxiao Pills]. / è—è¯å ­å‘³èƒ½æ¶ˆä¸¸è´¨é‡æ ‡å‡†çš„å»ºç«‹ä¸Žä¼˜åŒ–.

Objective: To establish quality standards for Liuwei Nengxiao pills, to optimize the quality control method, and to provide references for the quality control of Liuwei Nengxiao pills. Methods: Chebula, dried ginger, and Tibetan liqueur root in Liuwei Nengxiao pills of different batch numbers were analyzed by thin layer chromatography (TLC). Then, the content of chrysophanol in the preparation was determined by high performance liquid chromatography (HPLC). Furthermore, a series of methodological validation, including the investigation of the linear relationship, precision, stability, and reproducibility and sample recovery test, were performed to verify the reliability of the results. Results: The TLC identification method was easy to perform and demonstrated high specificity, clear spots, and good separation effect. In addition, the negative controls showed no interference. The HPLC method showed high accuracy. The results of methodological validation showed that the peak area of chrysophanol had a good linear relationship (r2=1.0) in the range of 0.06-0.80 µg, presenting good precision (with the relative standard deviation being lower than 2.0%), good stability and reproducibility (with the relative standard deviation being lower than 1.0%), and an average recovery rate of 100.8%. Conclusion: TLC and HPLC are easy to perform, showing high accuracy and reproducibility. The quality standards established are scientific, reasonable, stable, and feasible, providing references for the quality control of Liuwei Nengxiao pills.

Sub-5 nm Ultrathin In2O3 Transistors for High-Performance and Low-Power Electronic Applications.

Ultrathin oxide semiconductors are promising candidates for back-end-of-line (BEOL) compatible transistors and monolithic three-dimensional integration. Experimentally, ultrathin indium oxide (In2O3) field-effect transistors (FETs) with thicknesses down to 0.4 nm exhibit an extremely high drain current (104 µA/µm) and transconductance (4000 µS/µm). Here, we employ ab initio quantum transport simulation to investigate the performance limit of sub-5 nm gate length (Lg) ultrathin In2O3 FETs. Based on the International Technology Roadmap for Semiconductors (ITRS) criteria for high-performance (HP) devices, the scaling limit of ultrathin In2O3 FETs can reach 2 nm in terms of on-state current, delay time, and power dissipation. The wide bandgap nature of ultrathin In2O3 (3.0 eV) renders it a suitable candidate for ITRS low-power (LP) electronics with Lg down to 3 nm. Notably, both the HP and LP ultrathin In2O3 FETs exhibit superior energy-delay products as compared to those of other common 2D semiconductors such as monolayer MoS2 and MoTe2. These findings unveil the potential of ultrathin In2O3 in HP and LP nanoelectronic device applications.

[Research Process on the Combined Pollution of Microplastics and Typical Pollutants in Agricultural Soils].

As a new type of environmental persistent pollutant， microplastics can not only have adverse effects on the ecosystem but also form complex pollution with co-existing pollutants in the surrounding environment， resulting in higher ecological and health risks. Based on the perspective of agroecosystems， this study focused on the combined pollution of heavy metals， pesticides， and antibiotics， which are three typical pollutants of farmland soil， as well as microplastics and discussed the adsorption-desorption behavior of heavy metals， pesticides， and antibiotics on microplastics. The influence of the structure and properties of microplastics， the physicochemical properties of pollutants， and environmental conditions on the adsorption and desorption behavior of heavy metals， pesticides， and antibiotics on microplastics was discussed. The influence of microplastics on the bioavailability of heavy metals， pesticides， and antibiotics in farmland soil and the internal mechanism were expounded. The existing problems and shortcomings of current research were pointed out， and the future research direction was proposed. This study can provide a scientific reference for ecological risk assessment of the combined pollution of microplastics and typical pollutants in farmland soil.

The Effects of Processing Parameters during the Wire Arc Additive Manufacturing of 308L Stainless Steel on the Formation of a Thin-Walled Structure.

Wire arc additive manufacturing (WAAM) excels in producing medium to large components with a high deposition rate. Process optimization is crucial for uniform, defect-free components. This research employs orthogonal experimental design and response surface methodology (RSM) to control TIG WAAM-ed 308L stainless steel components. Varied parameters, including tungsten electrode angle, welding current, and speed, target weld bead attributes. Analysis of variance (ANOVA) evaluates multi-processing parameter influence on weld bead formation. Comparison with experimental results confirms accurate modeling of the relationship between parameters and bead attributes. The study optimizes process parameters and swing to enhance dimensional accuracy in single-layer and multi-layer components, improving precision, quality, and accuracy in thin-walled structures.

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up.

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

Immediate and delayed effects of environmental temperature on schizophrenia admissions in Liuzhou, China, 2013-2020: a time series analysis.

This study aimed to investigate the associations between environmental temperature and schizophrenia admissions in Liuzhou, China. A Poisson generalized linear model combined with a distributed lag nonlinear model was used to analyze the effects of daily mean temperature on schizophrenia admissions from 2013 to 2020 in Liuzhou. Additionally, subgroup analyses were conducted to investigate possible modifications stratified by gender, marital status, and age. In this study, 10,420 schizophrenia admissions were included. The relative risks of schizophrenia admissions increased as the temperature rose, and the lag effects of high temperature on schizophrenia admissions were observed when the daily mean temperature reached 21.65°C. The largest single effect was observed at lag0, while the largest cumulative effect was observed at lag6. The single effects of high temperatures on schizophrenia admissions were statistically significant in both males and females, but the cumulative effects were statistically significant only in males, with the greatest effect at lag0-7. The single effect of high temperatures on admissions for unmarried schizophrenics was greatest at lag5, while the maximum cumulative effect for unmarried schizophrenia was observed at lag0-7. The single effects of high temperatures on schizophrenia admissions were observed in those aged 0-20, 21-40, and 41-60. The cumulative effects for schizophrenics aged 21-40 were observed from lag0-3 to lag0-7, with the maximum effect at lag0-7. In conclusion, the risk of schizophrenia admissions increased as the environmental temperature increased. The schizophrenics who were unmarried appeared to be more vulnerable to the single and cumulative effects of high temperature.

Gold/Chiral Amine Relay Catalysis Enables Asymmetric Synthesis of C2-Quaternary Indolin-3-ones.

A mild and effective strategy for the asymmetric synthesis of C2-quaternary indolin-3-ones from 2-alkynyl arylazides and ketones by gold/chiral amine relay catalysis is described. In this reaction, 2-alkynyl arylazides undergo gold-catalyzed cyclization, nucleophilic attack, and oxidation to form intermediate 2-phenyl-3H-indol-3-ones, followed by an l-proline-catalyzed asymmetric Mannich reaction with ketones, to afford corresponding products in satisfactory yields with excellent enantio- and diastereoselectivities.

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes: A Meta-Regression of Acupuncture Randomized Controlled Trials.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.

Inducing enhanced neutralizing antibodies against broad SARS-CoV-2 variants through glycan-shielding multiple non-neutralizing epitopes of RBD.

Introduction: Since the outbreak of SARS-CoV-2, vaccines have demonstrated their effectiveness in resisting virus infection, reducing severity, and lowering the mortality rate in infected individuals. However, due to the rapid and ongoing mutations of SARS-CoV-2, the protective ability of many available vaccines has been challenged. Therefore, there is an urgent need for vaccines capable of eliciting potent broadly neutralizing antibodies against various SARS-CoV-2 variants. Methods: In this study, we developed a novel subunit vaccine candidate for SARS-CoV-2 by introducing a series of shielding glycans to the Fc-fused receptor-binding domain (RBD) of the prototypic spike protein. This approach aims to mask non-neutralizing epitopes and focus the immune response on crucial neutralizing epitopes. Results: All modified sites were confirmed to be highly glycosylated through mass spectrometry analysis. The binding affinity of the glycan-shielded RBD (gsRBD) to the human ACE2 receptor was comparable to that of the wildtype RBD (wtRBD). Immunizing mice with gsRBD when combined with either Freund's adjuvant or aluminum adjuvant demonstrated that the introduction of the glycan shield did not compromise the antibody-inducing ability of RBD. Importantly, the gsRBD significantly enhanced the generation of neutralizing antibodies against SARS-CoV-2 pseudoviruses compared to the wtRBD. Notably, it exhibited remarkable protective activity against Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), approximately 3-fold, 7- fold, and 17-fold higher than wtRBD, respectively. Discussion: Our data proved this multiple-epitope masking strategy as an effective approach for highly active vaccine production.

Theoretical study of protein adsorption on graphene/h-BN heterostructures.

The biological characteristics of planar heterojunction nanomaterials and their interactions with biomolecules are crucial for the potential application of these materials in the biomedical field. This study employed molecular dynamics (MD) simulations to investigate the interactions between proteins with distinct secondary structures (a single α-helix representing the minimal oligomeric domain protein, a single ß-sheet representing the WW structural domain of the Yap65 protein, and a mixed α/ß structure representing the BBA protein) and a planar two-dimensional heterojunction (a GRA/h-BN heterojunction consisting of a graphene nanoplate (GRA) and a hexagonal boron nitride nanoplate (h-BN)). The results indicate that all three kinds of protein can be quickly and stably adsorbed on the GRA/h-BN heterojunction due to the strong van der Waals interaction, regardless of their respective types, structures and initial orientations. Moreover, the proteins exhibit a pronounced binding preference for the hBN region of the GRA/h-BN heterojunction. Upon adsorption, the α-helix structure of the minimal oligomeric domain protein experiences partial or complete denaturation. Conversely, while the secondary structure of the single ß-sheet and mixed α/ß structure (BBA protein) undergoes slight changes (focus on the coil and turn regions), the main α-helix and ß-sheet structures remain intact. The initial orientation significantly impacts the degree of protein adsorption and its position on the GRA/h-BN heterojunction. However, regardless of the initial orientation, proteins can ultimately be adsorbed onto the GRA/h-BN heterojunction. Furthermore, the initial orientation has a minor influence on the structural changes of proteins. Significantly, the combination of different secondary structures helps mitigate the denaturation of a single α-helix structure to some extent. Overall, the adsorption of proteins on GRA/h-BN is primarily driven by van der Waals and hydrophobic interactions. Proteins with ß-sheet or mixed structures exhibit stronger biocompatibility on the GRA/h-BN heterojunction. Our research elucidated the biological characteristics of GRA/h-BN heterojunction nanomaterials and their interactions with proteins possessing diverse secondary structures. It offers a theoretical foundation for considering heterojunction nanomaterials as promising candidates for biomedical applications.

Dynamic monitoring of serum tumor markers as prognostic factors in patients with advanced non-small-cell lung cancer treated with first-line immunotherapy: a multicenter retrospective study.

Background: To date, no specific studies have reported the use of dynamic serum tumor markers (STMs) as prognostic factors in patients with advanced non-small-cell lung cancer (NSCLC) who receive first-line immunotherapy. Therefore, it is unclear whether STMs can be used as a prognostic factor for first-line immunotherapy in advanced NSCLC. Objectives: To elucidate the role of STMs in monitoring immunotherapy response in advanced NSCLC. Patients were treated with first-line programmed cell death-1/programmed cell death ligand-1 inhibitors at four Chinese centers. Design: This was a multicenter retrospective study. Methods: Blood samples were collected at baseline and after 6-8 weeks of treatment. Computed tomography scans were used to evaluate treatment efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Post-treatment drops in STMs [Serum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125)] were decreased ⩾20% (Group C) over baseline was used as cutoff level for defining a marker response. If STMs were increased by ⩾20% after treatment, the therapeutic effect was limited (Group A). Patients with STM changes between a 20% increase or decrease were enrolled in Group B. In univariate and multivariate stepwise Cox regression analyses, STMs and RECIST responses were analyzed for their impact on progression-free survival (PFS) and overall survival (OS). Results: The analysis included 716 patients. By multivariate analysis, CEA, NSE, CYFRA21-1, CA19-9, and CA125 (Group A versus Group B and Group A versus Group C) were associated with significant differences in PFS. Similar results were observed in the OS analysis. Similar results were observed in the adenocarcinoma subgroup analyses. In squamous cell carcinoma subgroup analyses, there was no statistical difference in PFS (p = 0.147) or OS (p = 0.068) between Group A and Group B for CA125. Conclusion: The increase and decrease in serum levels of STMs might be reliable prognostic factors for immunotherapy efficacy in NSCLC patients.

Acupuncture for in vitro fertilization-embryo transfer: an overview of systematic reviews. / é’ˆç¸è¾ åŠ©ä½“å¤–å—ç²¾èƒšèƒŽç§»æ¤çš„ç³»ç»Ÿè¯„ä»·å†è¯„ä»·.

OBJECTIVES: To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). METHODS: The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. RESULTS: A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. CONCLUSIONS: Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.

Use of Evidence-Based Research Approach in RCTs of Acupuncture-Related Therapies for Primary Dysmenorrhea: A Meta-Research.

OBJECTIVE: To assess the use of evidence-based research (EBR) approach in randomized controlled trials (RCTs) of acupuncture-related therapies for primary dysmenorrhea (PD). METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and China Science and Technology Journal Database were searched from January 2013 to December 2022 for RCTs of acupuncture on PD. The full text and references of each RCT were read to assess whether systematic reviews (SRs) or other types of studies with similar research questions and end-users' perspectives were cited to justify and design the trial. In addition, the discussion section were analyzed to evaluate whether trials placed the new result in the existing SRs to draw a conclusion. Multivariable logistic regression was used to find variables that associated with 3 aspects of EBR approach: (1) citing clinical studies for justification, (2) citing relevant studies that obtain the perspectives of end users, and (3) citing clinical studies for results discussion. RESULTS: Of 473 RCTs included, 45.67% (216) of the trials cited relevant similar studies, 21.56% (102) referenced to the studies that collected end-users' perspectives, and 10.99% (52) placed result in the context of the previous research. Few RCTs appropriately applied EBR approach. Among all the included studies, 3.17% (15) of the trials used SRs to inform study questions but none of them used updated SRs with acceptable quality; 1.05% (5) of the trials cited SRs of end-user's perspectives in the justification and design of the study, and only 1 trial added results in existing SR to draw a conclusion. Year of publication, language, funding, registration, ethical approval and number of sites were significantly associated with 1 of the 3 aspects of EBR approach. CONCLUSIONS: Few RCTs in acupuncture-related therapies for PD used the EBR approach to minimize research redundancy. Researchers, research institutes, funding agencies, ethics committees, journals and peer reviewers in acupuncture should make efforts to use and promote the EBR approach to ensure the value of new trials.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.