Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation.

Langerhans cells (LCs) play a pivotal role in skin homeostasis, and the heterogeneity of LCs has long been considered. In this study, we have identified two steady-state (LC1 and LC2) and two activated LC subsets in the epidermis of human skin and in LCs derived from CD34+ hemopoietic stem cells (HSC-LCs) by utilizing single-cell RNA sequencing and mass cytometry. Analysis of HSC-LCs at multiple time-points during differentiation revealed that EGR1 and Notch signaling were among the top pathways regulating the bifurcation of LC1 and LC2. LC1 were characterized as classical LCs, mainly related to innate immunity and antigen processing. LC2 were similar to monocytes or myeloid dendritic cells, involving in immune responses and leukocyte activation. LC1 remained stable under inflammatory microenvironment, whereas LC2 were prone to being activated and demonstrated elevated expression of immuno-suppressive molecules. We revealed distinct human LC subsets that require different developmental regulation and orchestrate reciprocal functions.

Flexible solar cells based on foldable silicon wafers with blunted edges.

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

Non-line-of-sight imaging using phasor-field virtual wave optics.

Non-line-of-sight imaging allows objects to be observed when partially or fully occluded from direct view, by analysing indirect diffuse reflections off a secondary relay surface. Despite many potential applications1-9, existing methods lack practical usability because of limitations including the assumption of single scattering only, ideal diffuse reflectance and lack of occlusions within the hidden scene. By contrast, line-of-sight imaging systems do not impose any assumptions about the imaged scene, despite relying on the mathematically simple processes of linear diffractive wave propagation. Here we show that the problem of non-line-of-sight imaging can also be formulated as one of diffractive wave propagation, by introducing a virtual wave field that we term the phasor field. Non-line-of-sight scenes can be imaged from raw time-of-flight data by applying the mathematical operators that model wave propagation in a conventional line-of-sight imaging system. Our method yields a new class of imaging algorithms that mimic the capabilities of line-of-sight cameras. To demonstrate our technique, we derive three imaging algorithms, modelled after three different line-of-sight systems. These algorithms rely on solving a wave diffraction integral, namely the Rayleigh-Sommerfeld diffraction integral. Fast solutions to Rayleigh-Sommerfeld diffraction and its approximations are readily available, benefiting our method. We demonstrate non-line-of-sight imaging of complex scenes with strong multiple scattering and ambient light, arbitrary materials, large depth range and occlusions. Our method handles these challenging cases without explicitly inverting a light-transport model. We believe that our approach will help to unlock the potential of non-line-of-sight imaging and promote the development of relevant applications not restricted to laboratory conditions.

Evaluation and Prediction Analysis of 3- and 5-Year Relative Survival Rates of Patients with Cervical Cancer: A Model-Based Period Analysis.

BACKGROUND: Cervical cancer remains a threat to female health due to high mortality. Clarification of the long-term trend of survival rate over time and the associated risk factors would be greatly informative to improve the prognosis of cervical cancer patients. METHODS: This retrospective study was based on data extracted from the Surveillance, Epidemiology, and End Results (SEER) database of the United States. The 3-year and 5-year overall survival rates of patients with cervical cancer during 2002-2006, 2007-2011, and 2012-2016 were analyzed. Period analysis was used to assess the variation in survival rate stratified by age, race, and socioeconomic status during the 15-year study period and then predicted the relative survival rate in the following period from 2017 to 2021. RESULTS: During 2002-2016, the 3-year relative survival rate of cervical cancer patients increased from 73.1% to 73.5% with a high jump between 2007 and 2011. This upward trend is expected to continue to 74.3% between 2017 and 2021. Patients older than 60 years, black ethnicity, or medium and high poverty status were likely to have a lower relative survival rate. CONCLUSION: This study confirmed the increased relative survival rate of cervical cancer patients over years and identified relevant risk factors. Targeted initiatives for elderly and socially underprivileged individuals may be able to mitigate inequality.

Why was the study conducted? Cervical cancer is one of the most common cancers endangering global women's health. Although there are currently relevant screening methods and vaccines, cervical cancer still leads to a higher risk of death in infected women and poses a serious threat to women's health. Therefore, it would be informative for future policy making if the risk factors affecting prognosis were assessed and the trend of long-term survival rate of patients with cervical cancer over time was predicted.What did the researchers do? We extracted data on cervical cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2002 and 2016 and used a model-based period analysis to assess the characteristics of the 3- and 5-year relative survival rates of cervical cancer patients stratified by age, race, and socioeconomic status. The relative survival rate for the period from 2017 to 2021 was projected.What did the researchers find? Our study found that the 3-year relative survival rate for cervical cancer patients increased from 73.1% to 73.5% between 2002 and 2016, with a jump between 2007 and 2011. Patients older than 60 years, those of black ethnicity, or those with medium and high poverty status were more likely to have a low relative survival rate.What do the findings mean? Our study confirms that the relative survival rate of cervical cancer patients has increased in recent years and has maintained an overall upward trend. Our findings suggest that age, race, and socioeconomic status are relevant risk factors. These findings would help us to predict future trends, better allocate medical resources, and optimize health policies to improve the prognosis of cervical cancer, such as targeting the elderly and other vulnerable groups.

Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Differential changes in the gut microbiota between extrinsic and intrinsic atopic dermatitis.

Elevated serum level of total and (or) allergen-specific IgE is one of the key features of atopic dermatitis (AD). Previous studies have shown that the gut microbiome mediates interactions between external exposures and the immune system in AD; however, the relationship between the gut microbiota and IgE remains unclear. In the present study, analyses of environmental exposures for 250 AD patients and 138 healthy volunteers revealed an association between hygiene levels in the residential environment and the occurrence of AD and the IgE level. Metagenomic sequencing of the gut microbiota from 68 AD patients and 77 healthy controls showed that AD patients had a distinct gut microbiota composition; moreover, while L-histidine degradation was enriched in healthy controls, L-histidine biosynthesis was enriched in AD patients. Extrinsic and intrinsic AD showed different enrichment patterns of specific microbes and differential associations of functional pathways. Our study indicated that elevated levels of IgE in AD were related to specific microbes in the gut microbiota, which showed extensive interactions with environmental factors.

miR-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting HDAC1 and promoting ER-α transcription.

OBJECTIVE: Metabolism is essential for bone development. The expressions of catabolic markers in chondrocytes show association with miR-34a-5p. This study discussed the mechanism by which miR-34a-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as well as bone metabolism. METHODS: Expressions of BMSC surface markers were determined via flow cytometry. Osteogenic differentiation of BMSCs was subsequently induced. miR-34a-5p mimic, oe-HDAC1, or ER-α activator Ferutinin was introduced in BMSCs. Alkaline phosphatase activity and calcification were detected. Expressions of miR-34a-5p, HDAC1, ER-α, and osteogenic markers were determined via RT-qPCR and Western blot. The binding relationship between miR-34a-5p and HDAC1 was verified by a dual-luciferase assay. Mice at the age of 6 months and 18 months were assigned to the young group and age group for in vivo experiments, and aged mice were treated with agomiR miR-34a-5p. Expressions of serum miR-34a-5p, HDAC1, ER-α, and bone metabolism markers in mice were determined. RESULTS: Osteogenic medium-induced BMSCs manifested increased expressions of miR-34a-5p and ER-α and decreased HDAC1 expression. miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs. miR-34a-5p targeted HDAC1. HDAC1 overexpression partially counteracted the promotional action of miR-34a-5p overexpression on osteogenic differentiation of BMSCs. miR-34a-5p overexpression activated ER-α. ER-α activator Ferutinin partially nullified the regulatory function of miR-34a-5p/HDAC1 on osteogenic differentiation of BMSCs. In vivo experiments showed that miR-34a-5p overexpression enhanced the potential of bone metabolism in aged mice. CONCLUSION: miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs and enhanced bone metabolism by promoting ER-α activation via targeting HDAC1.

Acute septic thrombophlebitis of the lower extremities due to foreign body injury and infection: a case report.

BACKGROUND: Septic thrombophlebitis (STP) of the lower extremities caused by foreign bodies is rare in the clinic, and the symptoms are serious. If the correct treatment is not implemented as soon as possible, the patient may progress to sepsis. CASE PRESENTATION: We report the case of a 51-year-old normally healthy male who developed fever 3 days after field work. When he was weeding with a lawn mower in the field, a metal foreign body from the grass flew into his left lower abdomen, resulting in an eschar on his left lower abdomen. He was diagnosed with scrub typhus but did not respond well to anti-infective treatment. After a detailed inquiry of his medical history and an auxiliary examination, the diagnosis was confirmed as STP of the left lower limb caused by a foreign body. After surgery, anticoagulation and anti-infection treatment, the infection and thrombosis were controlled, and the patient was cured and discharged. CONCLUSIONS: STP caused by foreign bodies is rare. Early detection of the aetiology of sepsis and early adoption of the correct measures can effectively block the progression of the disease and reduce the patient's pain. Clinicians should identify the source of sepsis through a medical history and clinical examination.

A general strategy to stabilize 1T-MoS2 using MXene heterostructures and unlock its hydrogen evolution reaction capabilities.

The two-dimensional (2D) metallic phase of MoS2, 1T-MoS2, has extraordinary electrical conductivity in contrast to the common 2D semiconducting phase, 2H-MoS2. However, the thermodynamic instabilities of 1T-MoS2 hinder its application. In this work, we investigate the possibilities of stabilizing 1T-MoS2 through heterostructure design using first-principles calculations. We found that MXene-based heterostructures could hamper phase transitions from 1T-MoS2 to 2H-MoS2 enabled by a larger phase transition kinetic energy barrier. Based on this finding, we propose a general and effective strategy for stabilizing 1T-MoS2, that is, building heterostructures using 1T-MoS2 and oxygen-functionalized MXenes. Besides, we have also observed that due to the occurrence of electron transfer in the heterostructure, 1T-MoS2 in the heterostructure exhibits improved hydrogen adsorption free energy and more active sites compared to the monolayer 1T-MoS2. These findings provide guidance for promoting and developing 1T-MoS2 for practical applications. In addition, the proposed heterostructure design strategy could inspire the study of phase transition behaviors and electrochemical properties of materials using interfaces.

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment.

ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

Why will we perform this study? Patients with advanced breast cancer in which the cancer cells have the receptor for the hormone estrogen and/or progesterone are typically treated with an aromatase inhibitor, a hormone therapy that decreases estrogen being made in the body, together with an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), a drug that blocks the growth of cancer cells. Although cancers usually respond to treatment initially, the cancer cells eventually change, so the drug combination no longer works. For example, mutation of the estrogen receptor (referred to as ESR1m) can stop aromatase inhibitors from working. Camizestrant is an investigational drug that blocks estrogen receptors, including mutated receptors, reducing the growth and spread of cancer. Here we describe the SERENA-6 clinical trial, which is testing camizestrant as a treatment for patients with breast cancer with ESR1m. How will we perform this research? The phase III SERENA-6 trial will use blood tests to monitor if patients with breast cancer develop ESR1m while being treated with an aromatase inhibitor and a CDK4/6 inhibitor. If ESR1m is detected, yet the disease is stable, participants will be randomly assigned to either continue with the same aromatase inhibitor or switch to camizestrant while continuing with the same CDK4/6 inhibitor. The study will assess whether switching to camizestrant prolongs the time before the cancer grows, spreads or worsens. It will also assess the length of time that participants live for versus those who continue with an aromatase inhibitor. Clinical Trial Registration: NCT04964934 (ClinicalTrials.gov).

Design, synthesis, and evaluation of JTE-013 derivatives as novel potent S1PR2 antagonists for recovering the sensitivity of colorectal cancer to 5-fluorouracil.

Targeting sphingosine-1-phosphate receptor 2 (S1PR2) has been proved as a promising strategy to reverse 5-fluorouracil (5-FU) resistance. Here, we report the discovery of the novel JTE-013 derivative compound 37 h as a more effective S1PR2 antagonist to reverse 5-FU resistance in SW620/5-FU and HCT116DPD cells than JTE-013 and previously reported compound 5. Compound 37 h could effectively bind S1PR2 and reduce its expression, thus leading to decreased expression of JMJD3 and dihydropyrimidine dehydrogenase (DPD), while also increasing the level of H3K27me3 to decrease the degradation of 5-FU and thereby increase its intracellular concentration in SW620/5-FU, HCT116DPD, and L02 cells. Furthermore, compound 37 h showed good selectivity to other S1PRs and normal colon cell line NCM460. Western blot analysis demonstrated that compound 37 h could abrogate the FBAL-stimulated upregulation of DPD expression by S1PR2. Importantly, compound 37 h also showed favorable metabolic stability with a long half-life (t1/2) of 7.9 h. Moreover, compound 37 h significantly enhanced the antitumor efficacy of 5-FU in the SW620/5-FU animal model. Thus, the JTE-013-based derivative compound 37 h represents a promising lead compound for the development of novel 5-FU sensitizers for colorectal cancer (CRC) therapy.

Discovery of new non-covalent and covalent inhibitors targeting SARS-CoV-2 papain-like protease and main protease.

Global coronavirus disease 2019 (COVID-19) pandemic still threatens human health and public safety, and the development of effective antiviral agent is urgently needed. The SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) are vital proteins in viral replication and promising therapeutic targets. Additionally, PLpro also modulates host immune response by cleaving ubiquitin and interferon-stimulated gene product 15 (ISG15) from ISGylated host proteins. In this report, we identified [1,2]selenazolo[5,4-c]pyridin-3(2H)-one and benzo[d]isothiazol-3(2H)-one as attractive scaffolds of PLpro and Mpro inhibitors. The representative compounds 6c and 7e exhibited excellent PLpro inhibition with percent inhibition of 42.9% and 44.9% at 50 nM, respectively. The preliminary enzyme kinetics experiment and fluorescent labelling experiment results determined that 6c was identified as a covalent PLpro inhibitor, while 7e was a non-covalent inhibitor. Molecular docking and dynamics simulations revealed that 6c and 7e bound to Zn-finger domain of PLpro. Compounds 6c and 7e were also identified to potent Mpro inhibitors, and they exhibited potent antiviral activities in SARS-CoV-2 infected Vero E6 cells, with EC50 value of 3.9 µM and 7.4 µM, respectively. In addition, the rat liver homogenate half-life of 6c and 7e exceeded 24 h. These findings suggest that 6c and 7e are promising led compounds for further development of PLpro/Mpro dual-target antiviral drugs.

Meta-analysis of downregulated E-cadherin as a diagnostic biomarker for cervical cancer.

OBJECTIVE: Downregulation of E-cadherin function or expression has been implicated in the progression of cervical cancer. This meta-analysis of updated publications was performed to assess the association of expression alteration of E-cadherin with disease severity and then to determine the diagnostic accuracy of E-cadherin in discriminating cervical lesions including cervical intraepithelial neoplasia (CIN) grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), and cervical cancer. METHODS: The articles published from inception to January 2021 were searched in PubMed, EBSCO, CNKI, and WanFang Database and then evaluated according to the criteria of meta-analysis. The eligible studies were retrieved and further analyzed. A bivariate mixed effects binary regression model was applied to determine pooled effect estimates. RESULTS: 16 studies with 2436 subjects from 7 countries were eligible for this meta-analysis. When compared with CIN1 control, the pooled odds ratios (ORs) with 95% confidence interval (CI) for the association of E-cadherin positivity with CIN2, CIN3, and cervical cancer were 0.34 (95% CI 0.23-0.51), 0.23 (95% CI 0.10-0.54), and 0.10 (95% CI 0.07-0.14), respectively. The pooled sensitivity and specificity for CIN3 or worse were 0.60 (95% CI 0.48-0.70) and 0.82 (95% CI 0.73-0.88) respectively, with the AUC of 0.78 (95% CI 0.74-0.82). Similar performance was found in CIN2 or worse. CONCLUSION: These findings demonstrated that the loss of E-cadherin protein was associated with worsened cervical lesions. E-cadherin might serve as a promising diagnostic biomarker to facilitate the discrimination of precancerous and cancerous lesions.

Assembly of Genome and Resequencing Provide Insights into Genetic Differentiation between Parents of Hulong Hybrid Grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂).

The Hulong hybrid grouper was bred from the brown-marbled grouper (Epinephelus fuscoguttatus) ♀ and the giant grouper (E. lanceolatus) ♂, combining the advantageous traits of both parents. Possessing an excellent performance, this hybrid's cultivation promotes the development of the grouper industry. Its male parent, the giant grouper, possesses the fastest growth and the largest body size among all coral-reef-dwelling fish. This species is not only an economically important species in marine aquaculture, but it is also an ideal male parent in the interspecific crossing of grouper species. In the present study, a high-quality chromosome-level genome of the giant grouper was constructed with a total length of 1.06 Gb, consisting of 24 chromosomes and 69 scaffolds. To analyze the genetic differences between the parents of the Hulong hybrid grouper, the structural variations (SVs) between both parental genomes were detected, and a total of 46,643 SVs were obtained. High-quality SNPs were identified from resequencing data. There were significant differences between the two genomes, and the average FST reached 0.685. A total of 234 highly differentiated regions were detected with an FST > 0.9. The protein-coding genes involved in SVs and highly differentiated regions were significantly enriched in metabolic pathways, including fatty metabolism, carbohydrate metabolism, amino acid metabolism and the TCA cycle. These genes may be related to the differences in feeding preferences and the ability to digest carbohydrates between the two grouper species under natural conditions. In addition, protein-coding genes related to the cell cycle and p53-signaling pathway were also detected. These genes may play important roles in the regulation of body size and growth performance. This research provides genomic resources for further breeding works and evolutionary analyses.

Inhibition of oocyte maturation by nitric oxide synthase 1 (NOS1) in zebrafish.

It is well-documented that nitric oxide (NO) is an important regulator of oocyte maturation in mammals. Conversely, the function of NO during oocyte maturation has received little attention in nonmammalian vertebrates. NO is produced from L-arginine through the action of the enzyme NO synthase (NOS). Herein, we examined the expression, hormonal regulation, and involvement of NOS in meiotic signaling in zebrafish oocyte maturation. Three types of nos genes, nos1, nos2a, and nos2b, have been identified in zebrafish. We found that the expression of nos1 was highest in the ovary among the three nos genes, with maximal expression in full-grown (FG)-stage follicles during folliculogenesis. In addition, the concentration of NO was reduced during oocyte maturation and this corresponded with the decreased expression of nos1 in the follicular cell layers, suggesting that NOS1-derived NO may be one of the inhibitors of oocyte maturation in zebrafish. This is the first description of nos1 involvement in oocyte maturation in vertebrates. Moreover, the NO donor SNAP (S-nitroso-l-acetyl penicillamine) partially attenuates human chorionic gonadotropin (hCG)- and 17,20ß-P-induced GVBD (germinal vesicle breakdown), perhaps by increasing cGMP levels during oocyte maturation. Finally, our results showed that SNAP and the cGMP analog 8-Br-cGMP inhibited hCG-induced mitogen-activated protein kinase (MAPK) activation, further indicating that NO and cGMP block oocyte maturation in zebrafish.

Identification of the Xyloglucan Endotransglycosylase/Hydrolase (XTH) Gene Family Members Expressed in Boehmeria nivea in Response to Cadmium Stress.

Xyloglucan endotransglycosylase/hydrolase (XTH) genes play an important role in plant resistance to abiotic stress. However, systematic studies of the response of Boehmeria nivea (ramie) XTH genes (BnXTHs) to cadmium (Cd) stress are lacking. We sought to identify the BnXTH-family genes in ramie through bioinformatics analyses and to investigate their responses to Cd stress. We identified 19 members of the BnXTH gene family from the ramie genome, referred to as BnXTH1-19, among which BnXTH18 and BnXTH19 were located on no chromosomes and the remaining genes were unevenly distributed across 11 chromosomes. The 19 members were divided into four groups, Groups I/II/IIIA/IIIB, according to their phylogenetic relationships, and these groups were supported by analyses of intron-exon structure and conserved motif composition. A highly conserved catalytic site (HDEIDFEFLG) was observed in all BnXTH proteins. Additionally, three gene pairs (BnXTH6-BnXTH16, BnXTH8-BnXTH9, and BnXTH17-BnXTH18) were obtained with a fragment and tandem-repeat event analysis of the ramie genome. An analysis of cisregulatory elements revealed that BnXTH expression might be regulated by multiple hormones and abiotic and biotic stress responses. In particular, 17 cisregulatory elements related to abiotic and biotic stress responses and 11 cisregulatory elements related to hormone responses were identified. We also found that most BnXTH genes responded to Cd stress, and BnXTH1, BnXTH3, BnXTH6, and BnXTH15 were most likely to contribute to the Cd tolerance of ramie, as evidenced by the substantial increases in expression under Cd treatment. Heterologous expression of BnXTH1, BnXTH6, and BnXTH15 significantly enhanced the Cd tolerance of transgenic yeast cells. These results suggest that the BnXTH gene family is involved in Cd stress responses, laying a theoretical foundation for functional studies of BnXTH genes and the innovative breeding of Cd-tolerant ramie.

Comparative Pharmacokinetics and Tissue Distribution of M10 and Its Metabolite Myricetin in Normal and Dextran-Sodium-Sulfate-Induced Colitis Mice.

M10, a novel myricetin derivative, is an anti-inflammatory agent designed for treatment of colitis. Here, we aim to investigate its pharmacokinetic behavior and tissue distribution in a mouse model with colitis. Pharmacokinetics and tissue distribution of M10 and its metabolite myricetin were compared in normal mice and in dextran-sodium-sulfate (DSS)-induced colitis mice. The role of fecal microbiota was also analyzed during metabolism of M10 in vitro. After oral administration, M10 was very low in the plasma of both normal and diseased mice. However, both M10 and myricetin were mainly distributed in the gastrointestinal tract, including the stomach, colon and small intestine, in physiological and pathological conditions. Significantly, M10 and myricetin were found in higher levels in gastrointestinal tracts with inflamed tissues than in normal tissues of mice. An in vitro assay revealed that 80% of M10 was metabolized to myricetin via fecal microbiota. After oral administration, M10 was not absorbed into circulation but mainly distributed in the inflamed submucosal tissues of colitic mice, where it was metabolized into myricetin to prevent colitis development.

Control of Hot Carrier Relaxation in CsPbBr3 Nanocrystals Using Damping Ligands.

In photon-conversion processes, rapid cooling of photo-induced hot carriers is a dominant energy loss channel. We herein report a 3-fold reduced hot carrier cooling rate in CsPbBr3 nanocrystals capped with a cross-linked polysiloxane shell in comparison to single alkyl-chain oleylamine ligands. Relaxation of hot charge carriers depends on the carrier-phonon coupling (CPC) process as an important channel to dissipate energies in nanostructured perovskite materials. The CPC strengths in the two samples were measured through cryogenic photoluminescence spectroscopic measurements. The effect of organic ligands on the CPC in CsPbBr3 nanocrystals is elucidated based on a damped oscillation model. This supplements the conventional polaron-based CPC model, by involving a damping effect on the CPC from the resistance of the ligands against nanocrystal lattice vibrations. The model also accounts for the observed linear temperature-dependence of the CPC strength. Our work enables predictions about the effect of the ligands on the performance of perovskite nanocrystals in future applications.

Autotransplantation of the ovarian cortex after in-vitro activation for infertility treatment: a shortened procedure.

STUDY QUESTION: Is it possible to establish a new in-vitro activation (IVA) protocol for infertility treatment? SUMMARY ANSWER: A new IVA procedure is an efficient and easily performed approach for infertility treatment of patients with diminished ovarian reserve (DOR). WHAT IS KNOWN ALREADY: IVA of primordial follicles with or without stimulators has been developed to treat patients with primary ovarian insufficiency (POI) successfully. However, the efficiency of the procedure is still very low. There is a requirement to optimize the protocol with increased efficiency for clinical application. STUDY DESIGN, SIZE, DURATION: Newborn mouse ovaries were used to establish a new 1-h IVA protocol with the mechanistic target of rapamycin (mTOR) stimulator phosphatidic acid (PA, 200 µM) and the phosphatidylinositol-3-kinase (PI3K) stimulator 740Y-P (250 µg/ml); a prospective observational cohort study in POI patients was performed on 15 POI patients and 3 poor ovarian response (POR) patients in three different centers of reproductive medicine in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: One-third of ovarian cortex was removed and processed into bigger strips (1 × 1 cm2, 1-2 mm thickness). Strips were then sutured back after treatment. The new approach only requires one laparoscopic surgery. MAIN RESULTS AND THE ROLE OF CHANCE: Follicular activation and development increased in cultured mouse and human ovarian tissues after 1 h of stimulator treatment. Compared with tiny ovarian cortex pieces (1 × 1 mm2), large ovarian strips (1 × 1 cm2) showed the lowest apoptotic signals after incubation. We applied the orthotropic transplantation procedure with large strips in the clinic, and 9 of 15 POI patients showed at least one-wave follicular growth during the monitoring period. One patient was reported with one healthy delivery after natural conception and another patient with a healthy singleton delivery after IVF. All the contacted patients (n = 13) responded with no side effects on their health 2-4 years after IVA procedure. LIMITATIONS, REASONS FOR CAUTION: Further clinical trials with a large number of well-defined patients are required to compare different IVA protocols. A long-term follow-up system should be set up to monitor patient's health in the future cohort study. WIDER IMPLICATIONS OF THE FINDINGS: By using stimulators, the findings in the study provide a more efficient IVA protocol for the treatment of patients with DOR. It requires only one laparoscopic surgery and thus minimizes patients' discomfort and costs. This strategy could be useful for patients diagnosed with POI and desire pregnancy as soon as possible after the operation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2018YFC1003703 and 2018YFC1004203); the National Natural Science Foundation of China (81871221); Co-construction of Provincial Department (201601006). The authors have no conflict of interest to disclose. TRIAL REGISTRATION NUMBER: ChiCTR2000030872.