Dietary sodium/potassium intake and cognitive impairment in older patients with hypertension: Data from NHANES 2011-2014.

This study aimed to assess the relationship between dietary sodium/potassium intake and cognition in elderly individuals with hypertension. We designed a cross-sectional study based on the 2011-2014 National Health and Nutrition Examination Survey (NHANES) 2011-2014. A multivariable-logistic regression analysis was performed to analyze the relationship between sodium/potassium intake and cognitive impairment. Restricted cubic spline (RCS) based on regression analysis to assess the nonlinear dose-response relationship between dietary sodium intake and cognitive performance. Out of the 2276 participants included in this study, 1670 patients had hypertension. Compared with the lowest quartile of dietary sodium intake, the lowest weighted odds ratio of cognitive impairment in DSST was observed in Q4 (OR = 0.45, 0.29-0.70), and a similar trend was observed in AFT (OR = 0.34, 0.18-0.65). After adjusting the covariates, the lowest weighted multivariable-adjusted OR of cognitive impairment in DSST were also observed in Q4 (OR = 0.47, 0.26-0.84) compared with the lowest quartile of dietary sodium intake. The RCS results showed that dietary sodium intake was U-shaped and associated with the risk of cognitive impairment in the DSST (Pnon-linearity  = 0.0067). In addition, no significant association was observed between dietary potassium intake and different dimensions of cognitive performance. In conclusion, excessively high and low low dietary sodium were associated with impairment of specific processing speed, sustained attention, and working memory for elderly patients with hypertension in the United States. However, no association was observed between dietary potassium intake and cognition.

The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma.

Aims: Transient receptor potential canonical-6 (TRPC6) is a therapeutic target for hepatocellular carcinoma. The authors aimed to synthesize and determine whether indole-2-carboxamide derivatives have anti-hepatocellular carcinoma activities targeting TRPC6. Materials & methods: Molecular docking was carried out to design these derivatives. The top five compounds were synthesized for activity validation using microscale thermophoresis. Cell cytotoxicity, flow cytometry, western blotting and cell transfection were used to investigate the anti-hepatocellular carcinoma activities and mechanisms in vitro. Xenografts of nude mice were used for in vivo evaluation. Results: The indole-2-carboxamide derivative, BP3112, promoted apoptosis and G1-phase arrest in HCCs via inhibiting TRPC6, and dose-dependently inhibit tumor growth in vivo. Conclusion: BP3112 as a specific inhibitor of TRPC6 is a potential therapeutic agent for hepatocellular carcinoma.

Effects of neoadjuvant radiochemotherapy for anorectal function in locally advanced rectal cancer patients: a study protocol for a prospective, observational, controlled, multicentre study.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision are standard treatment regimen for patients with locally advanced rectal cancer (LARC). This sphincter-saving treatment strategy may be accompanied by a series of anorectal functional disorders. Yet, prospective studies that dynamically evaluating the respective roles of radiotherapy, chemotherapy and surgery on anorectal function are lacking. PATIENTS/DESIGN: The study is a prospective, observational, controlled, multicentre study. After screening for eligibility and obtaining informed consent, a total of 402 LARC patients undergoing NCRT followed by surgery, or neoadjuvant chemotherapy followed by surgery, or surgery only would be included in the trial. The primary outcome measure is the average resting pressure of anal sphincter. The secondary outcome measures are maximum anal sphincter contraction pressure, Wexner continence score and low anterior resection syndrome (LARS) score. Evaluations will be carried out at the following stages: baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), and at follow-up visits (every 3 to 6 months, T4, T5……). Follow-up for each patient will be at least 2 years. DISCUSSION: We expect the program to provide more information of neoadjuvant radiotherapy and/or chemotherapy on anorectal function, and to optimize the treatment strategy to reduce anorectal dysfunction for LARC patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05671809). Registered on 26 December 2022.

Electrochemical assembly of single-walled carbon nanotube/polypyrrole/tellurium/lead telluride multi-layer nanocomposite films for room-temperature flexible thermoelectric application.

With the complexity and diversification of thermoelectric (TE) application scenarios, it becomes increasingly difficult for single-component thermoelectric materials to satisfy practical demands. Therefore, recent researches have largely focused on the development of the multi-component nanocomposites, which are probably a good solution for the TE application of some materials that are not eligible when used alone. In this work, a seires of single-walled carbon nanotube (SWCNT)/polypyrrole (PPy)/tellurium (Te)/lead telluride (PbTe) multi-layer flexible composite films were fabricated via the successive electrodeposition of the flexible PPy layer with a low thermal conductivity, the ultra-thin Te induction layer, and the brittle PbTe layer with a large Seebeck coefficient over the pre-fabricated SWCNT membrane electrode with a high electrical conductivity. Through the complementary advantages between different components and the multiple synergies of the interface engineering, the SWCNT/PPy/Te/PbTe composites harvested the excellent TE performance with a maximum power factor (PF) of 929.8 ± 35.4 µW m-1 K-2 at room temperature, outperforming those of most of the electrochemically-prepared organic/inorganic TE composites reported previously. This work evidenced that the electrochemical multi-layer assembly is a feasible tactic for constructing special thermoelectric materials to meet customized requirements, which could also be applied to other material platforms.

Characteristic Mapping for Ellipse Detection Acceleration.

It is challenging to characterize the intrinsic geometry of high-degree algebraic curves with lower-degree algebraic curves. The reduction in the curve's degree implies lower computation costs, which is crucial for various practical computer vision systems. In this paper, we develop a characteristic mapping (CM) to recursively degenerate 3n points on a planar curve of n th order to 3(n-1) points on a curve of (n-1) th order. The proposed characteristic mapping enables curve grouping on a line, a curve of the lowest order, that preserves the intrinsic geometric properties of a higher-order curve (ellipse). We prove a necessary condition and derive an efficient arc grouping module that finds valid elliptical arc segments by determining whether the mapped three points are colinear, invoking minimal computation. We embed the module into two latest arc-based ellipse detection methods, which reduces their running time by 25% and 50% on average over five widely used data sets. This yields faster detection than the state-of-the-art algorithms while keeping their precision comparable or even higher. Two CM embedded methods also significantly surpass a deep learning method on all evaluation metrics.

Piperlonguminine attenuates renal fibrosis by inhibiting TRPC6.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang (LWDH) is a classic prescription that has been used to the treatment of "Kidney-Yin" deficiency syndrome for more than 1000 years in China. Recent studies have confirmed that LWDH can prevent the progression of renal fibrosis. Numerous studies have demonstrated the critical role that TRPC6 plays in the development of renal fibrosis. Due to the complex composition of LWDH and its remarkable therapeutic effect on renal fibrosis, it is possible to discover new active ingredients targeting TRPC6 for the treatment of renal fibrosis. AIM OF STUDY: This study aimed to identify selective TRPC6 inhibitors from LWDH and evaluate their therapeutical effects on renal fibrosis. MATERIALS AND METHODS: Computer-aided drug design was used to screen the biologically active ingredients of LWDH, and their affinities to human TRPC6 protein were detected by microcalorimetry. TRPC6, TRPC3, and TRPC7 over-expressed HEK293 cells were constructed, and the selective activities of the compounds on TRPC6 were determined by measuring [Ca2+]i in these cells. To establish an in vitro model of renal fibrosis, human renal proximal tubular epithelial HK-2 cells were stimulated with TGF-ß1. The therapeutic effects of LWDH compounds on renal fibrosis were then tested by detecting the related proteins. TRPC6 was knocked-down in HK-2 cells to investigate the effects of LWDH active ingredients on TRPC6. Finally, a unilateral ureteral obstruction model of renal fibrosis was established to test the therapeutic effect. RESULTS: From hundreds of LWDH ingredients, 64 active components with oral bioavailability ≥30% and drug-likeness index ≥0.18 were acquired. A total of 10 active components were obtained by molecular docking with TRPC6 protein. Among them, 4 components had an affinity with TRPC6. Piperlonguminine (PLG) had the most potent affinity with TRPC6 and blocking effect on TRPC6-mediated Ca2+ entry. A 100 µM of PLG showed no detectable inhibition on TRPC1, TRPC3, TRPC4, TRPC5, or TRPC7-mediated Ca2+ influx into cells. In vitro results indicated that PLG concentration-dependently inhibited the abnormally high expression of α-smooth muscle actin (α-SMA), collagen I, vimentin, and TRPC6 in TGF-ß1-induced HK-2 cells. Consistently, PLG also could not further inhibit TGF-ß1-induced expressions of these protein biomarkers in TRPC6 knocked-down HK-2 cells. In vivo, PLG dose-dependently reduced urinary protein, serum creatinine, and blood urea nitrogen levels in renal fibrosis mice and markedly alleviated fibrosis and the expressions of α-SMA, collagen I, vimentin, and TRPC6 in kidney tissues. CONCLUSION: Our results showed that PLG had anti-renal fibrosis effects by selectively inhibiting TRPC6. PLG might be a promising therapeutic agent for the treatment of renal fibrosis.

Maternal emotional regulation strategy is associated with newborn feeding practices within 72 h after delivery: Cross sectional analyses of a multi-center study in China.

BACKGROUND: Early feeding practices have a great impact on the growth and development of infants, and the health of mothers. Maternal emotional regulation (ER) is closely related to infant feeding practices. Exploring the relationship between ER strategy and feeding practice can inform early exclusive breastfeeding (EBF) interventions. METHODS: Using baseline survey of a longitudinal study, 965 mothers in Chongqing municipality, Guangzhou city, and Huizhou city were enrolled. At baseline, the study used self-administrated questionnaires to investigate the socio-demographic characteristics, maternal ER strategies and feeding practice within 72 h of delivery. Chi-square test and logistic regression were used to determine the associations of the mothers' ER and feeding practices within 72 h postpartum. RESULTS: Among 965 participants, 27.8 % of mothers practiced EBF, and 69.5 % of mothers reported getting breastfeeding education from health providers. The average scores on the cognitive reappraisal and the expressive suppression of the ERQ were 29.95 ± 7.24 and 14.47 ± 5.16 respectively. Multivariable analysis showed women with expressive suppression were less likely to practice EBF (aOR = 0.96, 95%CI: 0.93-0.98, p = 0.002), while receiving breastfeeding education was positively associated with EBF (aOR = 1.52, 95%CI: 1.09-2.12, p = 0.013). LIMITATIONS: Because the study started during the COVID-19 pandemic, the lock-down measures paused recruitments for quite some time reducing the enrollment of participation. The data we used was within 72 h postpartum, hence the period of time to study feeding practices was short. CONCLUSION: Mothers' ER strategy and breastfeeding education need to be addressed as part of interventions designed to improve EBF rates during the newborn period in China.

Food-water-land-ecosystem nexus in typical Chinese dryland under different future scenarios.

Healthy coupling of the food-water-land-ecosystem (FWLE) nexus is the basis for achieving sustainable development (SD), and FWLE in drylands is frontier scientific issues in the study of coupled human land systems. To comprehensively safeguard the future food, water, and ecological security of drylands, this study examined the implications for FWLE linkages in a typical Chinese dryland from the perspective of future land-use change. First, four different land-use scenarios were proposed using a land-use simulation model with a gray multi-objective algorithm, including an SD scenario. Then, the variation of three ecosystem services was explored: water yield, food production, and habitat quality. Finally, redundancy analysis was used to derive the future drivers of FWLE and explore their causes. The following results were obtained. In the future in Xinjiang, under the business as usual scenario, urbanization will continue, forest area will decrease, and water production will decline by 371 million m3. In contrast, in the SD scenario, this negative impact will be substantially offset, water scarcity will be alleviated, and food production will increase by 1.05 million tons. In terms of drivers, the anthropogenic drivers will moderate the future urbanization of Xinjiang to some extent, with natural drivers dominating the sustainable development scenario by 2030 and a potential 22 % increase in the drivers of precipitation. This study shows how spatial optimization can help protect the sustainability of the FWLE nexus in drylands and simultaneously provides clear policy recommendations for regional development.

Effects of the construction of fertile and cultivated soil layer on soil fertility and maize yield in Albic soil.

We examined the effects of fertile soil layer construction technology on soil fertility and maize yield with a 3-year field experiment in Albic soil in Fujin, Heilongjiang Province. There were five treatments, including conventional tillage (T15, without organic matter return) and fertile soil layer construction methods [deep tillage (0-35 cm) with straw return, T35+S; deep tillage with organic manure, T35+M; deep tillage with straw and organic manure return, T35+S+M; deep tillage with straw, organic manure return and chemical fertilizer, T35+S+M+F]. The results showed that: 1) compared with the T15 treatment, maize yield was significantly increased by 15.4%-50.9% under fertile layer construction treatments. 2) There was no significant difference of soil pH among all treatments in the first two years, but fertile soil layer construction treatments significantly increased soil pH of topsoil (0-15 cm soil layer) in the third year. The pH of subsoil (15-35 cm soil layer) significantly increased under T35+S+M+F, T35+S+M, and T35+M treatments, while no significant difference was observed for T35+S treatment, compared with T15 treatment. 3) The fertile soil layer construction treatments could improve the nutrient contents of the topsoil and subsoil layer, especially in the subsoil layer, with the contents of organic matter, total nitrogen, available phosphorus, alkali-hydrolyzed nitrogen and available potassium being increased by 3.2%-46.6%, 9.1%-51.8%, 17.5%-130.1%, 4.4%-62.8%, 22.2%-68.7% under the subsoil layer, respectively. The fertility richness indices were increased in the subsoil layer, and nutrient contents of the subsoil layer were close to those of topsoil layer, indicating that 0-35 cm fertile soil layer had been constructed. 4) Soil organic matter contents in the 0-35 cm layer were increased by 8.8%-23.2% and 13.2%-30.1% in the second and third years of fertile soil layer construction, respectively. Soil organic carbon storage was also gradually increased under fertile soil layer construction treatments. 5) The carbon conversion rate of organic matter was 9.3%-20.9% under T35+S treatment, and 10.6%-24.6% under T35+M, T35+S+M, and T35+S+M+F treatments. The carbon sequestration rate was 815.7-3066.4 kg·hm-2·a-1 in fertile soil layer construction treatments. The carbon sequestration rate of T35+S treatment increased with experimental periods, and soil carbon content under T35+M, T35+S+M and T35+S+M+F treatments reached saturation point in the experimental second year. Construction of fertile soil layers could improve the fertility of topsoil and subsoil and maize yield. In term of economic benefits, combination application of maize straw, organic material and chemical fertilizer within 0-35 cm soil, cooperating with conservation tillage, is recommended for the Albic soil fertility improvement.

Dual-light defined in situ oral mucosal lesion therapy through a mode switchable anti-bacterial and anti-inflammatory mucoadhesive hydrogel.

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting the quality of life. Due to the moist and highly dynamic oral lining, the existing oral mucoadhesives are unable to serially address the challenges of residency, hemorrhage, bacterial infection and inflammatory reaction. Herein, a dual-light defined oral mucoadhesive (ZPTA-G/HMA) was proposed, with a methacrylate gelatin-methacrylate hyaluronic acid (GelMA-HAMA, G/HMA) double network hydrogel as a matrix, tannic acid (TA) as a high content anchor moiety provider for the moist oral mucosa, and polydopamine modified zinc oxide (ZnO@PDA, ZP) as a photocatalytic antibacterial substance. This platform had good adhesive and hemostatic properties both in vitro and in vivo. Under 520 nm green light (GL) irradiation, ZPTA-G/HMA would anchor to the wet mucosa surface by crosslinking and exert broad-spectrum antibacterial ability (even including Candida albicans) by in situ producing reactive oxygen species (ROS). Moreover, under 808 nm near-infrared (NIR) irradiation, the increased release of TA combined with the photothermal effect of ZP endowed ZPTA-G/HMA with enhanced anti-inflammatory and pro-healing performance. Collectively, ZPTA-G/HMA could be switched by light sources to achieve the dual-mode real-time adjustment of in situ anti-bacterial function and controlled anti-inflammation, combined with ideal mucosal residence, thus promising in developing personalized sequential strategies for varied oral mucosal lesions.

Electrostatic Epitaxy of Orientational Perovskites for Microlasers.

Orientational growth of single-crystalline structures is pivotal in the semiconductor industry, which is achievable by epitaxy for producing thin films, heterostructures, quantum wells, and superlattices. Beyond silicon and III-V semiconductors, solution-processible semiconductors, such as metal-halide perovskites, are emerging for scalable and cost-effective manufacture of optoelectronic devices, whereas the polycrystalline nature of fabricated structures restricts their application toward integrated devices. Here, electrostatic epitaxy, a process sustained by strong electrostatic interactions between self-assembled surfactants (octanoate anions) and Pb2+ , is developed to realize orientational growth of single-crystalline CsPbBr3 microwires. Strong electrostatic interactions localized at the air-liquid interface not only support preferential nucleation for single crystallinity, but also select the crystal facet with the highest Pb2+ areal density for pure crystallographic orientation. Due to the epitaxy at the air-liquid interface, direct growth of oriented single-crystalline microwires onto different substrates without the processes of lift-off and transfer is realized. Photonic lasing emission, waveguide coupling, and on-chip propagation of coherent light are demonstrated based on these single-crystalline microwires. These findings open an avenue for on-chip integration of single-crystalline materials.

Comparision of nitrogen removal characteristic and microbial community in freshwater and marine recirculating aquaculture systems.

Recirculating aquaculture system (RAS) has a good prospect in aquaculture, but its nitrogen removal characteristics and microbial community changes in freshwater and marine water remain unclear. In this study, six RAS were designed and divided into freshwater group and marine water group with salinity of 0‰ and 32‰, respectively, and operated for 54 days to test changes in nitrogen (NH4+-N, NO2--N, NO3--N), extracellular polymeric substances and microbial communities. The results showed that ammonia nitrogen was rapidly reduced and almost converted to nitrate nitrogen in the freshwater RAS but to nitrite nitrogen in marine RAS. Compared with freshwater RAS, marine RAS had lower tightly bound extracellular polymeric substances and worse stability and settleability condition. 16S rRNA amplicon sequencing reflected significantly lower bacterial diversity and richness in marine RAS. Microbial community structure at phylum level showed lower relative abundance of Proteobacteria, Actinobacteria, Firmicutes, Nitrospirae, but higher abundance of Bacteroidetes under a salinity of 32‰. High salinity decreased the abundance of funtional genera (Nitrosospira, Nitrospira, Pseudomonas, Rhodococcus, Comamonas, Acidovorax, f_Comamonadaceae), which may account for nitrite accumulation and low nitrogen removal capacity in marine RAS. These findings could provide theoretical and practical basis for improving the start-up speed of high-salinity nitrification biofilm.

In vitro and in vivo bioaccessibility, antioxidant activity, and color of red radish anthocyanins as influenced by different drying methods.

This study aims to examine the effects of various drying methods, namely vacuum freeze drying (VFD), vacuum drying (VD), hot air drying (HAD), sun drying (SD), and air-impingement jet drying (AIJD), on in vitro and in vivo bioaccessibility of red radish anthocyanins. By color parameters, VFD- and AIJD-dried red radish showed redder color to HAD-, SD-, and VD-dried red radish. SEM images of dried red radish showed multiple holes and loose interior structure. Forty-six anthocyanins were identified in red radish. Original, in vitro and in vivo digestive samples from VFD-dried red radish contained more anthocyanins and were more bioaccessibility than fresh and other dried red radishes. In vitro and in vivo research revealed that dried red radish showed weaker and stronger FRAP and ABTS·+ scavenging activities than fresh red radish. Colon content of mice had significantly higher FRAP and ABTS·+ scavenging activities than the stomach, small intestine, and cecum contents.

Investigation of bacterial and fungal population structure on environmental surfaces of three medical institutions during the COVID-19 pandemic.

Objectives: To evaluate the population structure of environmental bacteria and fungi in three different types of medical institutions and the potential risks due to antibiotic resistance during the coronavirus disease 2019 (COVID-19) pandemic. Methods: One hundred twenty-six environmental surface samples were collected from three medical institutions during the COVID-19 pandemic. A total of 6,093 and 13,514 representative sequences of 16S and ITS ribosomal RNA (rRNA) were obtained by amplicon sequencing analysis. The functional prediction was performed using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States tool based on the Greengenes database and the FAPROTAX database. Results: On environmental surfaces in three medical institutions during the COVID-19 pandemic, Firmicutes (51.6%) and Bacteroidetes (25%) were the dominant bacteria, while Ascomycota (39.4%) and Basidiomycota (14.2%) were the dominant fungi. A number of potential bacterial and fungal pathogens were successfully identified by the metagenomic approach. Furthermore, compared with the bacterial results, the fungi showed a generally closer Bray Curtis distance between samples. The overall ratio of Gram-negative bacteria to Gram-positive bacteria was about 3:7. The proportion of stress-tolerant bacteria in medical institutions A, B and C reached 88.9, 93.0 and 93.8%, respectively. Anaerobic bacteria accounted for 39.6% in outdoor environments, 77.7% in public areas, 87.9% in inpatient areas and 79.6% in restricted areas. Finally, the ß-Lactam resistance pathway and polymyxin resistance pathway were revealed through functional prediction. Conclusion: We described the microbial population structure changes in three different types of medical institutions using the metagenomic approach during the COVID-19 pandemic. We found that the disinfection measures performed by three healthcare facilities may be effective on the "ESKAPE" pathogens, but less effective on fungal pathogens. Moreover, emphasis should be given to the prevention and control of ß-lactam and polymyxin antibiotics resistance bacteria during the COVID-19 pandemic.

High prevalence of fluconazole resistant Candida tropicalis among candiduria samples in China: An ignored matter of concern.

Introduction: The rapid rise of azole resistance in Candida tropicalis causing invasive infections has become a public health concern; however, the prevalence of resistant isolates in urine samples was not well studied, because the clinical significance of candiduria was not unambiguous due to possible host colonization. Methods: We performed a 12-year laboratory-based surveillance study of C. tropicalis causing either invasive infection or candiduria and studied their susceptibility profiles to common antifungal drugs. The complete coding domain sequence of the ERG11 gene was amplified in all fluconazole resistant isolates, and aligned with the wild-type sequence to detect nucleotide mutations. Results: A total of 519 unique C. tropicalis strains isolates, 69.9% of which were isolated from urine samples and remaining 30.1% were invasive strains. Overall, 16.5% isolates were confirmed to be resistant to fluconazole, of which 91.9% were cross-resistant voriconazole. Of note, at the beginning of surveillance (2010-2011), the fluconazole resistance rates were low in both candiduria and invasive groups (6.8% and 5.9%, respectively). However, the resistant rate in the candiduria group significantly increased to 29.5% since 2012-2013 (p = 0.001) and stayed high since then, whilst the resistance rate in the invasive group only showed a gradually increasing trends till 2021 (p > 0.05). Sequence analysis of ERG11 from fluconazole-resistant strains revealed the prevalence of A395T/W mutations were relatively low (16.7%) in the beginning but reached 87.5-100% after 2014. Moreover, the A395W heterozygous mutation isolates became predominant (>60% of resistant strains) after 2016, and indeed isolates carrying corresponding amino acid substitution (Y132F) was highly resistant to fluconazole with MIC50 exceeded 256 µg/ml. Conclusion: Our study revealed high azole resistant rate in candiduria with its increasing trends observed much earlier than stains causing invasive infections. Given antimicrobial resistance as a critical "One Health" issue, the emergence of antifungal resistance in Candida species that are common commensal colonizers in the human body should be concerned.

Regioselective Multisite Atomic-Chlorine Passivation Enables Efficient and Stable Perovskite Solar Cells.

Passivating defects using organic halide salts, especially chlorides, is an effective method to improve power conversion efficiencies (PCEs) of perovskite solar cells (PSCs) arising from the stronger Pb-Cl bonding than Pb-I and Pb-Br bonding. However, Cl- anions with a small radius are prone to incorporation into the perovskite lattice that distorts the lead halide octahedron, degrading the photovoltaic performance. Here, we substitute atomic-Cl-containing organic molecules for widely used ionic-Cl salts, which not only retain the efficient passivation by Cl but also prevent the incorporation of Cl into the bulk lattice, benefiting from the strong covalent bonding between Cl atoms and organic frameworks. We find that only when the distance of Cl atoms in single molecules matches well with the distance of halide ions in perovskites can such a configuration maximize the defect passivation. We thereby optimize the molecular configuration to enable multiple Cl atoms in an optimal spatial position to maximize their binding with surface defects. The resulting PSCs achieve a certified PCE of 25.02%, among the highest PCEs for PSCs, and retain 90% of their initial PCE after 500 h of continuous operation.

Cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC: Evidence from China.

Objective: We aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China. Methods: A partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results. Results: Compared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained. Conclusion: The results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan-Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.

Cloning and rational modification of a cold-adapted esterase for phthalate esters and parabens degradation.

Phthalate esters (PAEs) and parabens are environmental pollutants that can be toxic to human health. Herein, a cold-adapted esterase from the Mao-tofu metagenome named Est1260 was screened for its PAE-hydrolyzing potential in cold temperatures. The results showed that purified Est1260 could degrade a variety of PAEs and parabens at temperatures as low as 0 °C. After careful analysis of the structural information and molecular docking, site-saturation mutation was conducted at the identified hotspots. Protein expression of variant A1B6 doubled, and its thermal stability significantly improved (24 times) without sacrificing activity at low temperatures. In addition, Est1260 and its variants were activated by NaCl and demonstrated resistance to high concentrations of saline (up to 5 M), making it a potential biocatalyst for bioremediation of PAE and paraben-polluted environments.

A pseudo-outbreak of Cyberlindnera fabianii funguria: Implication from whole genome sequencing assay.

Background: Although the yeast Cyberlindnera fabianii (C. fabianii) has been rarely reported in human infections, nosocomial outbreaks caused by this organism have been documented. Here we report a pseudo-outbreak of C. fabianii in a urology department of a Chinese hospital over a two-week period. Methods: Three patients were admitted to the urology department of a tertiary teaching hospital in Beijing, China, from Nov to Dec 2018, for different medical intervention demands. During the period Nov 28 to Dec 5, funguria occurred in these three patients, and two of them had positive urine cultures multiple times. Sequencing of rDNA internal transcribed spacer (ITS) region and MALDI-TOF MS were applied for strain identification. Further, sequencing of rDNA non-transcribed spacer (NTS) region and whole genome sequencing approaches were used for outbreak investigation purpose. Results: All the cultured yeast strains were identified as C. fabianii by sequencing of ITS region, and were 100% identical to the C. fabianii type strain CBS 5640T. However, the MALDI-TOF MS system failed to correctly identify this yeast pathogen. Moreover, isolates from these three clustered cases shared 99.91%-100% identical NTS region sequences, which could not rule out the possibility of an outbreak. However, whole genome sequencing results revealed that only two of the C. fabianii cases were genetically-related with a pairwise SNP of 192 nt, whilst the third case had over 26,000 SNPs on its genome, suggesting a different origin. Furthermore, the genomes of the first three case strains were phylogenetically even more diverged when compared to a C. fabianii strain identified from another patient, who was admitted to a general surgical department of the same hospital 7 months later. One of the first three patients eventually passed away due to poor general conditions, one was asymptomatic, and other clinically improved. Conclusion: In conclusion, nosocomial outbreaks caused by emerging and uncommon fungal species are increasingly being reported, hence awareness must be raised. Genotyping with commonly used universal gene targets may have limited discriminatory power in tracing the sources of infection for these organisms, requiring use of whole genome sequencing to confirm outbreak events.

APOC1 as a novel diagnostic biomarker for DN based on machine learning algorithms and experiment.

Introduction: Diabetic nephropathy is the leading cause of end-stage renal disease, which imposes a huge economic burden on individuals and society, but effective and reliable diagnostic markers are still not available. Methods: Differentially expressed genes (DEGs) were characterized and functional enrichment analysis was performed in DN patients. Meanwhile, a weighted gene co-expression network (WGCNA) was also constructed. For further, algorithms Lasso and SVM-RFE were applied to screening the DN core secreted genes. Lastly, WB, IHC, IF, and Elias experiments were applied to demonstrate the hub gene expression in DN, and the research results were confirmed in mouse models and clinical specimens. Results: 17 hub secretion genes were identified in this research by analyzing the DEGs, the important module genes in WGCNA, and the secretion genes. 6 hub secretory genes (APOC1, CCL21, INHBA, RNASE6, TGFBI, VEGFC) were obtained by Lasso and SVM-RFE algorithms. APOC1 was discovered to exhibit elevated expression in renal tissue of a DN mouse model, and APOC1 is probably a core secretory gene in DN. Clinical data demonstrate that APOC1 expression is associated significantly with proteinuria and GFR in DN patients. APOC1 expression in the serum of DN patients was 1.358±0.1292µg/ml, compared to 0.3683±0.08119µg/ml in the healthy population. APOC1 was significantly elevated in the sera of DN patients and the difference was statistical significant (P > 0.001). The ROC curve of APOC1 in DN gave an AUC = 92.5%, sensitivity = 95%, and specificity = 97% (P < 0.001). Conclusions: Our research indicates that APOC1 might be a novel diagnostic biomarker for diabetic nephropathy for the first time and suggest that APOC1 may be available as a candidate intervention target for DN.