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A novel long-wavelength fluorescence probe NBP has been developed for the detection of nitroreductase (NTR) and hypoxia. NBP could be activated by NTR at 0.1 μM to release the fluorophore NBF and significant changes in fluorescence emission at 658 nm were observed. This feature makes it advantageous for imaging hypoxic cells with minimal endogenous interference. [ABSTRACT FROM AUTHOR]

The title compound, [Zn(C8H6N4O3)] n or [Zn( L)] n [H2 L is 3-(6-oxo-6,9-dihydro-1 H-purin-1-yl)propionic acid], crystallized as a nonmerohedral twin. The ZnII cation is four-coordinated, ligated by two carboxylate O atoms from two L ligands and two N atoms from another two ligands. Each ligand bridges four ZnII centres, extending the structure into a three-dimensional polymer with a 4-connected (65,41) topological structure containing two-dimensional homochiral layers constructed from one-dimensional metal-organic helices. Investigation of the thermal stability of the compound shows that the network has very high thermostability and is stable up to 720 K. [ABSTRACT FROM AUTHOR]

Abstract: Nanostructured ZnO powders with various morphologies have been prepared by the hydrothermal and chemical precipitation methods. Our results reveal that these nanostructured ZnO particles exhibit obvious room-temperature ferromagnetism, while microbipods show paramagnetic behavior. Photoluminescence spectra indicate that oxygen vacancies (Vo) exsit in these nanostructured ZnO particles. The polarized impurity band associated with Vo defects provides the necessary ferromagnetic coupling, and the variable concentrations of Vo result in the tunable magnetic behaviors in these nanostructured ZnO particles. [Copyright &y& Elsevier]

• A mathematical model of HIV multiple infection is developed. • The model includes both sequential virus infection and cell-to-cell transmission. • The model is fit to the distribution data of proviral viral genomes in infected cells. • Cell-to-cell transmission is shown to play a role in multiple infection formation. • Relative contributions from different routes of infection are evaluated. Multiple infection of target cells by human immunodeficiency virus (HIV) may lead to viral escape from host immune responses and drug resistance to antiretroviral therapy, bringing more challenges to the control of infection. The mechanisms underlying HIV multiple infection and their relative contributions are not fully understood. In this paper, we develop and analyze a mathematical model that includes sequential cell-free virus infection (i.e. one virus is transmitted each time in a sequential infection of target cells by virus) and cell-to-cell transmission (i.e. multiple viral genomes are transmitted simultaneously from infected to uninfected cells). By comparing model prediction with the distribution data of proviral genomes in HIV-infected spleen cells, we find that multiple infection can be well explained when the two modes of viral transmission are both included. Numerical simulation using the parameter estimates from data fitting shows that the majority of T cell infections are attributed to cell-to-cell transmission and this transmission mode also accounts for more than half of cell's multiple infections. These results suggest that cell-to-cell transmission plays a critical role in forming HIV multiple infection and thus has important implications for HIV evolution and pathogenesis. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) Growth-Arrest Associated LncRNA 1 (GASL1) is a lncRNA with a suppressive role in glioma, prostate carcinoma and gastric carcinoma, whereas its involvement in esophageal cancer is unknown. In the present study, we used RT-qPCR to detect the expression of GASL1 in esophageal cancer cell carcinoma (ESCC) cell lines, and constructed the overexpression and interference plasmids of GASL1 and the interference plasmid of DKK1. CCK8 was used to detect the cell proliferation level, clone formation experiment was used to detect the cell clonal formation ability, flow cytometry was used to detect the cell cycle level, and wound healing and Transwell experiments were respectively used to detect the cell invasion and migration. The interference and overexpression plasmids of GASL1 were injected into mice subcutaneously for tumor-bearing experiment. The body weight, tumor growth curve, and tumor weight of mice were recorded, and western blot was used to detect the expression of proliferation-, invasion-, and migration-related proteins and the expression of Wnt3a/β-catenin signal-related proteins in tumor tissues. LncRNA GASL1 was down-regulated in ESCC cell lines, and GASL1 inhibited ESCC cell progression and regulated cell cycle arrest in ESCC cells. In vivo , GASL1 inhibited tumor growth. GASL1 decreased the protein levels of DDK1, Wnt3a, β-catenin, and c-MYC in ESCC cell lines. Interfering DKK1 activates Wnt3a/β--catenin signal to reverse the inhibitory effects of GASL1 on proliferation, cell cycle acceleration, invasion, and migration. In conclusion, lncRNA GASL1 regulates cell migration, invasion and cell cycle stagnation by inactivating the wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs)-based regenerative medicine provides unprecedented therapeutic potential in neural insults. However, NSC-based neurogenesis is strongly influenced by the inflammatory environment after injury, which is mainly modulated by macrophages' secretion effects. In this study, we adopted poly L-lactic acid (PLLA) aligned fibers to guide macrophages elongating along the fiber directions and polarizing phenotypically toward anti-inflammatory M2 type. 7,8-DHF was loaded within the fibers with a sustained and controlled release pattern to promote the polarization of the macrophages and secretion of various anti-inflammatory factors. NSCs showed enhanced neuronal differentiation in the presence of the conditioned medium (CM) from M2 macrophages cultured on the 7,8-DHF-loaded PLLA aligned fibers. Moreover, M2-CM promoted neurogenesis by enhancing neurite outgrowth of NSC-derived neurons. In summary, we provided a novel therapeutic strategy for NSC neurogenesis by manipulating macrophage classification into anti-inflammatory M2 phenotypes with the 7,8-DHF-loaded PLLA aligned fibers, existing potential applications in treating neural injuries. • We provided a strategy of manipulating macrophage polarization toward M2 phenotypes by aligned fibers loaded 7,8-DHF. • Macrophages of elongated morphology tended to secrete pro-inflammatory factors. • M2-CM promoted neuronal differentiation and neurite outgrowth of neural stem cell. • NSC neurogenesis can be promoted by manipulating macrophage classification into anti-inflammatory M2 phenotypes. [ABSTRACT FROM AUTHOR]

To offer a roadmap for companies to achieve best practices, a new green-ranking system has been launched by the CDP, formerly the Carbon Disclosure Project. This new system, which takes its data from firms' disclosure of their own carbon-reduction efforts, classifies companies into four ranks, namely, A (leadership), B (management), C (awareness) and D (disclosure), where a higher ranking indicates a greener company. This system replaced the old carbon-disclosure scoring system. However, as participation in the survey that collects the data is voluntary, there is a concern that the carbon disclosure could be a green-washing activity, used for impression management. It is not clear whether this new system can resolve this issue. This study investigates whether corporate green rankings are more closely associated with carbon reduction than carbon-disclosure scoring. We use innovative methods to detect green-washing behaviour by examining the degree of correlation between carbon disclosure and performance versus between green rank and performance. Our empirical results show that there a significant positive link between green ranking and carbon performance, whereas a positive association between disclosure scoring and carbon performance is not found under the old carbon-reporting mechanism. This likely means that this new system has to a certain extent reduced green washing in our sample firms, among other implications. [ABSTRACT FROM AUTHOR]

Background: As it is less known about the prevalence and characteristics of pain in the patients with interstitial lung disease (ILD), this paper aims at determining the characteristics of the pain in the patients with ILD.Methods: Subjects with ILD and health controls with the matched ages and genders completed Short Form McGill Pain Questionnaire (SF-MPQ) and part of the Brief Pain Inventory (BPI) Short Form to elicit the characteristics of the pain. The patients with ILD were also assessed through Pulmonary Function Test, Six Minutes Walking Test (6MWT), modified Medical Research Council Dyspnea Scale (mMRC) for state of the illness and measured health-related quality of life (HRQoL) by Short Form-36 (SF-36) and psychological associations by Hospital Anxiety and Depression Scale (HADS).Results: A total of 63 subjects with ILD and 63 healthy controls (HC) were recruited in our study. The prevalence of the pain was 61.9% in ILD versus 25.3% in HC (P = 0.005) and the median score of the pain rank index (PRI) in ILD was higher than that in HC (P = 0.014). Chest (46.1%) accounted for the highest of overall pain locations in subjects with ILD. Associated clinical factors for pain intensity in the patients with ILD included exposure history of risk factors of ILD, with a longer distance of 6MWD (≥ 250 m), and a higher mMRC score (2-4). The patients with ILD and pain are more likely to suffer impaired HRQoL (P = 0.0014) and psychological problems (P = 0.0017, P = 0.044).Conclusion: The pain is common in those with ILD and the pain intensity is associated with exposure history, 6MWD, and mMRC score. The patients with ILD and pain were possibly to suffer depression, anxiety, and impaired HRQoL. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that microRNAs (miRs) are involved in the pathogenesis of colorectal cancer (CRC); however, the roles of miR-590-5p in CRC are not completely understood. Therefore, the present study investigated the expression of miR-590-5p and programmed cell death 4 (PDCD4) in CRC tissues and healthy adjacent tissues via reverse transcription-quantitative PCR. Furthermore, human CRC cells were cultured in vitro and transfected with miR-590-5p inhibitor. CRC cell viability, migration and invasion were evaluated by conducting MTT, wound healing and Transwell assays, respectively. Additionally, the relative expression of PDCD4 and phosphorylated-Smad2/3 was analyzed via western blotting. miR-590-5p was significantly upregulated and PDCD4 was significantly downregulated in CRC tissues compared with healthy adjacent tissues. Moreover, the results indicated that miR-590-5p knockdown inhibited cell viability and migration by altering the expression of PDCD4, transforming growth factor-β and phosphorylated-Smad2/3. PDCD4 was identified as a direct target of miR-590-5p. In conclusion, the results of the present study suggested that miR-590-5p may regulate CRC cell viability and migration, indicating that miR-590-5p may serve as a potential therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

We prove that the number of 01-fillings of a given stack polyomino (a polyomino with justified rows whose lengths form a unimodal sequence) with at most one 1 per column which do not contain a fixed-size northeast chain and a fixed-size southeast chain, depends only on the set of row lengths of the polyomino. The proof is via a bijection between fillings of stack polyominoes which differ only in the position of one row and uses the Hecke insertion algorithm by Buch, Kresch, Shimozono, Tamvakis, and Yong and the jeu de taquin for increasing tableaux of Thomas and Yong. Moreover, our bijection gives another proof of the result by Chen, Guo, and Pang that the crossing number and the nesting number have a symmetric joint distribution over linked partitions. [ABSTRACT FROM AUTHOR]

• The mitochondrial genomes of three Ascaris populations were sequenced. • The Ascaris populations sequenced in this study were all gathered in cluster B. • The human-type and hybrid Ascaris populations belonged to different sub-clusters. • Ascaris populations were geographically isolated before host shift in China. Ascaris lumbricoides and Ascaris suum are parasitic nematodes in human and pig intestines. The two species can cross infect and produce hybrids, which contribute to the controversy concerning the taxonomy of A. lumbricoides and A. suum. The purpose of this study was to investigate the microevolutionary process and evolutionary history of human-type Ascaris, pig-type Ascaris, and hybrid Ascaris and provide a theoretical basis for the prevention and control of human and animal ascariasis. The mitochondrial phylogenomics of human-type Ascaris (n = 5), pig-type Ascaris (n = 6), and hybrid Ascaris (n = 6) populations were analyzed using high-throughput sequencing technology. The mitochondrial genomes of human-type Ascaris , pig-type Ascaris , and hybrid Ascaris contained 36 genes (atp 8 was missing), including 12 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. All genes were located on the heavy chain. The initiation codons used for protein-coding genes were ATT and TTG and the termination codons were TAA and TAG. The base distribution showed obvious AT preference. The phylogenetic tree based on the Ascaris mitochondrial genomes showed three main clusters (A, B, and C). The Ascaris populations sequenced in this study were all gathered in cluster B. The human-type and hybrid Ascaris populations belonged to different sub-clusters, but the pig-type Ascaris population was more scattered. The mitochondrial genome sequences of the 17 Ascaris individuals in this study did not differ much. The results of this study indicate that Ascaris populations were geographically isolated before host shift. In addition, the data show that there are differences between hybrid Ascaris, human-type Ascaris, and pig-type Ascaris. The information has important theoretical significance and application value. [ABSTRACT FROM AUTHOR]

Burns on human skin often leads to slow recovery because of continuous wound infections caused by the loss of skin protection. In this study, a seed-free soaking method is put forward to prepare PCL@ZIF-8/εPL nanofibers as a dressing for burn wounds. This ZIF-8-coated polycaprolactone (PCL) fiber exhibits increased specific surface area, significantly increasing the polypeptide loading of epsilon polylysine (εPL) from 12 to 20 wt.%. The antibacterial experiment found that ZIF-8 and εPL exhibited dual antibacterial properties, and after εPL was loaded to ZIF-8, the nanofiber demonstrated stronger antibacterial properties that can better kill the remaining tenacious bacteria. This high-efficiency bactericidal property, combined with the ability to protect wounds from common infections by bacteria in the air, would promote wound healing, shortening the healing time period from 24 to 17 days. Further tissue sections confirm that the shielding effect and dual antibacterial properties of the composite fiber membrane are the reasons behind the acceleration of the healing of burns and scalds. Shielding and antibacterial material are helpful for the treatment of burns and scalds, and it may also guide the treatment of other types of wounds. [ABSTRACT FROM AUTHOR]

Sulfadiazine (SDZ) is a kind of anti-degradable antibiotics that is commonly found in wastewater, but its removal mechanism and transformation pathway remain unclear in microalgal systems. This study investigated the effects of initial algae concentration and SDZ-induced stress on microalgal growth metabolism, SDZ removal efficiency, and transformation pathways during Chlorella sp. cultivation. Results showed that SDZ had an inhibitory effect on the growth of microalgae, and increasing the initial algal biomass could alleviate the inhibitory effect of SDZ. When the initial algal biomass of Chlorella sp. was increased to 0.25 g L−1, the SDZ removal rate could reach 53.27%–89.07%. The higher the initial algal biomass, the higher the SOD activity of microalgae, and the better the protective effect on microalgae, which was one of the reasons for the increase in SDZ removal efficiency. Meanwhile, SDZ stress causes changes in photosynthetic pigments, lipids, total sugars and protein content of Chlorella sp. in response to environmental changes. The main degradation mechanisms of SDZ by Chlorella sp. were biodegradation (37.82%) and photodegradation (23%). Most of the degradation products of SDZ were less toxic than the parent compound, and the green algae were highly susceptible to SDZ and its degradation products. The findings from this study offered valuable insights into the tradeoffs between accumulating microalgal biomass and antibiotic toxic risks during wastewater treatment, providing essential direction for the advancement in future research and full-scale application. [Display omitted] • The SDZ removal of Chlorella sp. under different induced stress reached up to 89%. • Photodegradation and biodegradation proved to be the primary SDZ removal pathways. • A high initial algae biomass can mitigate growth inhibition of SDZ induced stress. • SDZ could enhance SOD enzyme and trigger the stress protection mechanism in algae. • Most of SDZ degradation products were less toxic than their parent compounds. [ABSTRACT FROM AUTHOR]

• By combining asymmetric polymerase chain reaction (PCR) and SERS, a highly-selective detection for EGFR mutation genes in lung cancer was developed. • This combined asymmetric PCR-SERS method had a high detection threshold (4.24 fM). • In the further detection in 15 blood samples, the asymmetric PCR-SERS method had an overall sensitivity of 75% and specificity of 100%. The evaluation of EGFR mutation genes in circulating tumor DNA (ctDNA) in blood sample is key for patients with lung cancer. Surface-enhanced Raman scattering (SERS) has potential for trace detection of DNA or RNA. The detection rate offered by current methods can not meet clinical demand. By combining asymmetric polymerase chain reaction (PCR) and SERS, a highly-selective detection for EGFR mutation genes in lung cancer was developed. Sea-urchin like Au nanoclusters (AuNCs) were synthesized via Ag seed-mediated growth. AuNCs with a diameter of 120 nm were covered with 79 nanopricks (20 nm). Then, EGFR mutation specific molecular beacons (MBs) labeled with Cy3 were coated on the surface of AuNCs. The loading amount of MBs was calculated as 5720 ± 740 on one AuNCs. These AuNCs probes had good efficiency (equilibrium time: 20 minutes) with high sensitivity (detection limit: 5.8 nM), high specificity (capable of single-base mismatch recognition) and good stability against nucleases. Following this, asymmetric PCR was performed to obtain large numbers of single-stranded DNA (ssDNA, E746-A750del). The ssDNA was incubated with the AuNCs probes and tested quantitatively based on the SERS signals of the AuNCs probes. This combined asymmetric PCR-SERS method had a very high detection threshold (4.24 fM). The asymmetric PCR-SERS method was shown to have an overall sensitivity of 75% and specificity of 100% in a further 15 clinical blood samples. This method is proved to be promising for non-invasive and sensitive detection of EGFR mutations in ctDNA. [ABSTRACT FROM AUTHOR]

A novel dual-emission fluorescence probe has been developed for specific and sensitive detection of hypochlorite (ClO−). Upon addition of ClO−, significant changes in fluorescence emission intensity at two discrete wavelengths were observed. Meanwhile OONO− led to only a single-channel fluorescence enhancement. This feature makes it a clear advantage in distinguishing ClO−, RNS from other ROS. [ABSTRACT FROM AUTHOR]

Inverted positive‐intrinsic‐negative (p‐i‐n) perovskite solar cells (IPSCs) have attracted widespread attention due to their low fabrication temperature, good stability in ambient air, and the potential for use in flexible and tandem devices. In recent years, self‐assembled monolayers (SAMs) have been investigated as a promising hole‐selective contact for IPSCs, leading to an impressive record efficiency of about 26%, which is comparable to that of the regular n‐i‐p counterparts. This review focuses on the progress of SAM‐based IPSCs from the perspective of energy level matching, defect passivation, interface carrier extraction, and SAMs’ stability improvement, as well as the advances in up‐scalable fabrication of SAMs and perovskite layers for efficient solar modules and tandem devices. A cost analysis of the SAMs and other commonly used hole‐selective materials is conducted to evaluate their cost‐effectiveness for photovoltaic applications. Finally, the future challenges are pointed out and the perspectives on how to up‐scale SAM‐based IPSCs and improve their long‐term operational stability are provided. [ABSTRACT FROM AUTHOR]

AbstractGlobal population growth and demographic restructuring are driving the food and agriculture sectors to provide greater quantities and varieties of food, of which protein resources are particularly important. Traditional animal-source proteins are becoming increasingly difficult to meet the demand of the current consumer market, and the search for alternative protein sources is urgent. Microbial proteins are biomass obtained from nonpathogenic single-celled organisms, such as bacteria, fungi, and microalgae. They contain large amounts of proteins and essential amino acids as well as a variety of other nutritive substances, which are considered to be promising sustainable alternatives to traditional proteins. In this review, typical approaches to microbial protein synthesis processes were highlighted and the characteristics and applications of different types of microbial proteins were described. Bacteria, fungi, and microalgae can be individually or co-cultured to obtain protein-rich biomass using starch-based raw materials, organic wastes, and one-carbon compounds as fermentation substrates. Microbial proteins have been gradually used in practical applications as foods, nutritional supplements, flavor modifiers, and animal feeds. However, further development and application of microbial proteins require more advanced biotechnological support, screening of good strains, and safety considerations. This review contributes to accelerating the practical application of microbial proteins as a promising alternative protein resource and provides a sustainable solution to the food crisis facing the world. [ABSTRACT FROM AUTHOR]

Inspired by the ubiquitous prevalence of 3‐hydroxyoxindoles in natural products and pharmaceuticals, we herein disclose a direct and practical transition‐metal‐free asymmetric hydroxylation using commercially available Davis enantiopure oxaziridines as efficient oxidants, expeditiously affording an array of medicinally active 3‐functionalized 3‐hydroxy‐2‐oxindoles bearing quaternary stereocenters. The protocol features cheap reactants, ease of operation, scalability, and good functional‐group tolerance and efficient formal synthesis of natural products. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells. Methods: Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK). Results: Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20−, Jurkat: CD19−CD20−) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed. Conclusions: The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established. Here, we screened the FANCI gene, which encodes a key component for FA pathway activation, in our whole-exome sequencing database of 1030 patients with idiopathic POI, and identified two pairs of novel compound heterozygous variants, c.[97C > T];[1865C > T] and c.[158-2A > G];[c.959A > G], in two POI patients, respectively. The missense variants did not alter FANCI protein expression and nuclear localization, apart from the variant c.158-2A > G causing abnormal splicing and leading to a truncated mutant p.(S54Pfs*5). Furthermore, the four variants all diminished FANCD2 ubiquitination levels and increased DNA damage under replication stress, suggesting that the FANCI variants impaired FA pathway activation and replication stress response. This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function. [ABSTRACT FROM AUTHOR]

A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core–shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0–400 μM with a detection limit of 2.78 μM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples. [ABSTRACT FROM AUTHOR]

Summary: Total antioxidant capacity (TAC) holds immense importance in evaluating the milk quality. However, achieving accuracy and comparability in TAC measurement requires a thorough examination of detection methods and the constituents of antioxidants. This research focussed on developing TAC evaluation system tailored for processed milk, and the applicability of four assays (ABTS, FRAP, DPPH and ORAC) was examined, considering their compatibility with antioxidants. For fractionated milk, defatting and deproteinisation processes targeted reduced fat‐soluble (phospholipids by 88.75%) and water‐soluble (ascorbic acid and riboflavin by 55.22% and 63.85%) components, respectively. ORAC assay proved effective for detecting deproteinised milk, whereas DPPD assay displayed heightened sensitivity to alterations in milk fat antioxidants. Regarding pressure‐ and heat‐treated milk, homogenisation increased the availability of phosphatidylcholine (36.59–57.53 mg/L) and sphingomyelin (5.56–10.35 mg/L). However, the TAC of heat‐treated milk experienced a significant reduction due to the degradation of various fat‐soluble antioxidants. ORAC and ABTS assays were found suitable for assessing homogenised and heat‐treated milk, respectively. The peroxide value of reconstituted processed milk fell within the range of 98.48%–104.57% compared to untreated whole milk, affirming the accuracy of key antioxidants and detection methods. This study provides valuable insights for the meticulous assessment and enhancement of antioxidant capacity in milk. [ABSTRACT FROM AUTHOR]

Herein, the preparation process, morphology, structure, and magnetic properties of La1.85Sr0.15CuO4 (LSCO) cobweb-like nanofibers are reported. LSCO nanofibers with a regular grain size distribution are successfully prepared via electrospinning, followed by calcination. We conducted morphology analysis and elemental distribution using electron microscopy and energy-dispersive X-ray spectroscopy (EDS), respectively. Additionally, magnetic property testing was performed using a vibrating sample magnetometer (VSM) to confirm the superconducting properties of the samples. Interestingly, our samples exhibited a superconducting transition temperature, Tc, of 25.21 K, which showed some disparity compared to similar works. Furthermore, we observed a ferromagnetic response at low temperatures in the superconducting nanofibers. We attribute these phenomena to the effects generated by surface states of nanoscale superconducting materials. [ABSTRACT FROM AUTHOR]

Temporal expectation refers to the capacity to allocate resources at a particular point in time, enabling us to enhance our behavior performance. Empirical evidence indicates that, among younger adults, temporal expectation can be driven by rhythm (i.e., regular sequences of stimuli). However, whether there are age-related changes in rhythm-based temporal expectation has not been clearly established. Furthermore, whether tempo can influence the relationship between rhythm-based temporal expectation and aging remains unexplored. To address these questions, both younger and older participants took part in a rhythm-based temporal expectation task, engaging three distinct tempos: 600 ms (fast), 1800 ms (moderate), or 3000 ms (slow). The results demonstrated that temporal expectation effects (i.e., participants exhibited significantly faster responses during the regular trials compared to the irregular trials) were observed in both the younger and older participants under the moderate tempo condition. However, in the fast and slow tempo conditions, the temporal expectation effects were solely observed in the younger participants. These findings revealed that rhythm-based temporal expectations can be preserved during aging but within a specific tempo range. When the tempo falls within the range of either being too fast or too slow, it can manifest age-related declines in temporal expectations driven by rhythms. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (TanIIA) and gene therapy both hold promising potentials in hepatocellular carcinoma (HCC) treatment. However, low solubility and poor bioavailability of TanIIA limit its clinical application. Similarly, gene therapy with GPC3-shRNA, a type of short hairpin RNAs (shRNAs) capable of silencing the glypican-3 (GPC3) expression, is seriously limited due to its susceptibility to nuclease degradation and high off-target effects. In the present study, polyethyleneimine (PEI)-polyethylene glycol (PEG)-coated mesoporous silica nanoparticles (MSN-PEG) were used as a drug carrier. By encapsulating TanIIA into MSN-PEG, we synthesized MSN-TanIIA-PEG nanoparticles and observed the involved characteristics. This was followed by exploration of antitumor activity on the HepG2 cell lines in vitro. Meanwhile, in order to construct GPC3-shRNA plasmids, a shRNA sequence targeting GPC3 was synthesized and cloned into the pSLenti-U6 vector. Accordingly, the performance of MSN-PEG as a gene transfer carrier for GPC3-shRNA gene therapy of HCC in vitro was evaluated, including transfection efficiency and DNA binding biological characteristics. The results indicated successful encapsulation of TanIIA in MSN-PEG, which had satisfactory efficacy, favorable dispersity, suitable particle size, and sustained release effect. The in vitro anti-HCC effects of nano-TanIIA were greatly improved, which outperformed free-TanIIA in terms of proliferation and invasion inhibition, as well as apoptosis induction of HCC cells. As expected, MSN-PEG possessed excellent gene delivery capacity with good binding, release, and protection from RNase digestion. Using MSN-PEG as a gene carrier, the plasmids were successfully transfected into HepG2 cells, and both the mRNA and protein expressions of GPC3 were significantly downregulated. It was thus concluded that a sustained release TanIIA delivery system for HCC treatment was synthesized and that MSN-PEG could also serve as a gene transfer carrier for gene therapy. More interestingly, MSN-PEG may be a potential delivery platform that combines TanIIA and GPC3-shRNA together to enhance their synergistic effect. [ABSTRACT FROM AUTHOR]

An association between obesity and deep vein thrombosis (DVT) has been revealed by observational studies, but it is not clear if the observed associations are causal, caused by confounding bias or reverse causation. We performed a two-sample Mendelian Randomization (MR) study by obtaining exposure and outcome data from separate published studies. We utilized data from Genetic Investigation of Anthropometric Traits (GIANT, 339,224 participants) consortium and FinnGen project (FinnGen, 1785 DVT case and 84,462 control participants) to determine the causal effect of BMI on DVT. All three MR methods provided a positive association between BMI and DVT. Using IVW, we found evidence of causal relationships between BMI and DVT. BMI is positively associated with DVT (IVW odds ratio [OR] per SD increase in BMI = 1.67 [95% CI, 1.16–2.40]; P = 0.006). MR Egger and weighted median regression also showed directionally similar estimates (MR-Egger OR per SD increase in BMI, 2.50 [95% CI, 1.07–5.84], P = 0.034; weighted median OR per SD increase in BMI, 2.02 [95% CI, 1.10–3.71], P = 0.023). Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed between BMI and DVT. Our findings provide evidence of significant causal association between BMI and DVT in agreement with observational studies. Taking measures to reduce the proportion of obesity may help reduce the incidence of DVT. • Association between BMI and DVT has been observed in the many observational studies. • Significant causal association between BMI and DVT was observed in the present study. • Taking measures to reduce the proportion of obesity may help reduce incidence of DVT. [ABSTRACT FROM AUTHOR]

The detection of chemical messenger molecules, such as neurotransmitters in nervous systems, demands high sensitivity to measure small variations, selectivity to eliminate interferences from analogues, and compliant devices to be minimally invasive to soft tissue. Here, an organic electrochemical transistor (OECT) embedded in a flexible polyimide substrate is utilized as transducer to realize a highly sensitive dopamine aptasensor. A split aptamer is tethered to a gold gate electrode and the analyte binding can be detected optionally either via an amperometric or a potentiometric transducer principle. The amperometric sensor can detect dopamine with a limit of detection of 1 μM, while the novel flexible OECT-based biosensor exhibits an ultralow detection limit down to the concentration of 0.5 fM, which is lower than all previously reported electrochemical sensors for dopamine detection. The low detection limit can be attributed to the intrinsic amplification properties of OECTs. Furthermore, a significant response to dopamine inputs among interfering analogues hallmarks the selective detection capabilities of this sensor. The high sensitivity and selectivity, as well as the flexible properties of the OECT-based aptasensor, are promising features for their integration in neuronal probes for the in vitro or in vivo detection of neurochemical signals. [ABSTRACT FROM AUTHOR]

Drug resistance can hamper the success of antiviral therapy for virus infection. Many mathematical models studying within-host drug resistance only consider two viral strains: wild-type (or drug-sensitive) and drug-resistant strains. However, the level of drug resistance can be continuous. Using HIV infection as an example, we developed a new within-host viral dynamic model that structures the virus population continuously on the basis of the level of drug resistance. We derived the basic reproduction number, which was shown to completely determine the global stability of the steady states. This model serves as a new continuous modeling framework to study the emergence and evolution of drug resistance during the therapy of virus infection. [ABSTRACT FROM AUTHOR]

The freezing and thawing of construction concrete is becoming an increasingly important structural challenge. In this study, a shrinkage-compensating concrete based on a double expansive admixture was developed and its frost resistance was assessed through rapid freezing and thawing cycling. The frost resistance of the concrete was derived through the measurement and calculation of the relative dynamic modulus of elasticity (RDME) and the mass loss rate (MLR), and the freezing- and thawing-cycle microstructures and products of concretes with different expansive agents were analyzed using scanning electron microscopy (SEM). It was shown that changes in the properties of the concrete under freezing and thawing could be divided into three stages: slow-damage stage, fast-damage stage, and stable stage. Compared to concrete without an expansive agent, a single-expansive-agent concrete demonstrated excellent frost resistance during the slow-damage stage, but the frost resistance rapidly decreased during the fast-damage age. After 150 cycles (the stable-damage stage), the concrete with a U-type expansive agent (UEA): MgO expansive agent (MEA) mix proportion of 2:1 had the best frost resistance, with RDME and MLR values 17.35% higher and 25.1% lower respectively, than that of an expansive-agent-free concrete. These test results provide a basis for the study of frost resistance in large-scale hydraulic concrete structures. [ABSTRACT FROM AUTHOR]

• Highly porous Mo 2 C/C is prepared using the N, K co-activated biochar as carbon source and matrix. • The obtained porous Mo 2 C/C shows a large specific surface area with nitrogen doping. • The porous architecture with a large specific surface area can afford abundant catalytic sites. • The interconnected N-rich carbon matrix provides efficient electron transfer pathways for HER. Molybdenum carbide (Mo 2 C) has offered great promise to serve as a platinum substitute towards efficient hydrogen evolution reaction (HER). However, both the lack of exposed catalytic sites and strong Mo–H binding strength will strongly hinder the HER process for Mo 2 C-based electrocatalysts. Herein, a scalable strategy is proposed for the preparation of highly porous Mo 2 C/C electrocatalysts with a specific surface area up to 611 m2 g−1 as well as uniform nitrogen doping derived from N, K co-activated biochar (NKAB). And the porous architecture with a large specific surface area can afford abundant catalytic sites. Additionally, both the Mo 2 C and carbon matrix are doped with nitrogen effectively, which can optimize the hydrogen adsorption free energy of Mo 2 C/C electrocatalysts associated with a higher intrinsic activity. As a result, the active site density and intrinsic activity of Mo 2 C/NKAB have been promoted simultaneously on account of the high specific surface area and nitrogen doping. Furthermore, the interconnected N-rich carbon matrix provides efficient electron transfer pathways for superior HER kinetics. Ultimately, the overall HER performances of Mo 2 C/NKAB can be significantly enhanced. [ABSTRACT FROM AUTHOR]

Two new luminescent CPs based on resorcin[4]arene and dicarboxylic acid have been rationally synthesized, and they featured highly sensitive and selective luminescent sensing for Fe3+ and Cr 2 O 7 − ions. • Two resorcin[4]arene-based coordination polymers were rationally designed. • 1 and 2 were used for the efficient luminescent detection of Fe3+ and Cr 2 O 7 − ions. • This work provided a possible way for the design of the luminescent sensors. Two luminescent cadmium(II) coordination polymers, [Cd 2 (L)(BDC) 2 ]·3DMF·5EtOH (1) and [Cd 2 (L)(OH-BDC) 2 ]·2DMF·6MeOH (2), have been solvothermally prepared with resorcin[4]arene-based ligand (L) and dicarboxylic acids (H 2 BDC = isophthalic acid, OH-H 2 BDC = 5-OH-isophthalic acid and N , N ′-dimethylformamide). 1 and 2 are isostructural and feature fascinating layer structures. Remarkably, 1 and 2 showed intense luminescent properties and were used as highly efficient multiple luminescent detection for Fe3+ and Cr 2 O 7 2− ions. [ABSTRACT FROM AUTHOR]

This paper is concerned with the following Choquard equation − △ u + (ω − β | x | ) u = (I α ∗ | u | N + α N − 2 ) | u | N + α N − 2 − 2 u , x ∈ R N , where N ≥ 3 , α ∈ (0 , N) , I α is the Riesz potential, ω and β are positive real numbers. For β = 0 , it is known that the above equation has no nontrivial solution. For β > 0 , − β ∕ | x | is called the external Coulomb potential. If 0 < β < c (α , ω , N) , we obtain a ground state solution of Pohoz̆aev type for the above equation, where c (α , ω , N) is a constant that can be expressed explicitly via α , ω and N. [ABSTRACT FROM AUTHOR]

Tungsten phosphide (WP) has attracted increasing attention in hydrogen evolution reaction (HER) due to its unique catalytic and electronic properties. However, its high preparation temperature often leads to particle excess growth and coarsening. Although tremendous efforts have been made to enlarge the surface areas and reduce particle size, the required high preparation temperature still limits its development. Herein, a facile self-exothermic reduction strategy under an extremely low temperature (300 °C) is proposed to prepare the ultra-fine WP nanoparticles with rich W vacancies. Remarkably, as revealed by XRD, TEM, ICP-OES and XPS analysis, the crystallinity, W vacancies and electron distribution of WP can be well controlled. The W vacancies can activate the neighboring P atoms and the bridge sites as active sites for HER, but also will change the electron distribution, which in turn deteriorates the conductivity of WP. By means of controllable W vacancies, the optimized low crystalline WP catalyst with a moderate number of W vacancies can be obtained, exhibiting a superior HER activity in acidic solution with a small Tafel slope (52 mV dec−1), which are smaller than most of WP-based catalysts and among the best records. Furthermore, this work will open a new horizon for both preparation and HER performance improvement of other transition metal phosphides. Image 1 • WP was successfully synthesized under an extremely low temperature of 300 °C. • The crystallinity, W vacancies and electron distribution of WP were regulated. • The balance between rich active sites and the good conductivity of WP is achieved. • The optimal LC-WP exhibited a superior HER performance and excellent stability. [ABSTRACT FROM AUTHOR]

Odontoblasts forms dentin as the main hard tissue of the tooth. Autophagy is a highly conserved homeostasis involved in odontoblast differentiation. DSPP (Dentin sialophosphoprotein) and Cbfα1 (Core binding factor α1) are typical factors in odontoblasts of the dentin-pulp complex. However, the relationship between Cbfα1 and DSPP as well as the role of Cbfα1 involved in the autophagy during odontoblast differentiation are poorly understood. In this study, we found the stimulation with FGF2 in MDPC-23 cells resulted in the suppression of autophagy and promotion of cell differentiation. We demonstrated that both mRNA and protein levels of Cbfα1 and DSPP were elevated upon FGF2 stimulation coupled with the inhibition of autophagy in MDPC-23 cells. Further results revealed that overdose of Cbfα1 increased the expression of DSPP, and also suppressed autophagy in MDPC-23 cells. Using luciferase reporter assay and EMSA, we illustrated that Cbfα1 upregulated DSPP expression through binding to the specific sites 5′-TACCTCA (-3950 bp to -3944 bp) and 5′-ACCACA (-3106 bp to -3101 bp) in DSPP promoter. Furthermore, ChIP assay results revealed that FGF2 treatment enhanced this binding of Cbfα1 to DSP P promoter. Signaling pathway inhibitor screening further revealed Cbfα1 suppressed autophagy involved in Wnt I signaling. Moreover, knockdown of Cbfα1 using siRNA silencing approach reversed the FGF2-mediated suppression of autophagy in MDPC-23 cells. Thus, these findings illustrate a novel regulatory mechanism by which Cbfα1 transcriptionally enhances DSPP expression, and also provide an insight into the inhibitory action of Cbfα1 in autophagy thereby facilitating odontoblast differentiation upon FGF2 stimulation. [ABSTRACT FROM AUTHOR]

Water pollution caused by heavy metals is a severe environmental issue. In this work, a graphene oxide–starch composite (GO/WS) was facilely prepared via hydrothermal process. The as-prepared GO/WS was characterized and employed as adsorbent to remove Cu(II). The removal performance was evaluated, and the adsorption mechanism was analyzed. Result shows that GO/WS outperforms either single graphene oxide (GO) or water soluble starch (WS) in terms of adsorption capacity. Specifically, GO/WS (D = 500 mg L−1) adsorbs 542.01 mg g−1 of Cu(II) (C0 = 300 mg L−1) in 24 min, exhibiting some advantages as higher capacity and shorter equilibrium time over other similar adsorbents. Adsorption complies with the Freundlich model and PSO model and is controlled by surface reaction, exhibiting favorable and chemical feature. Moreover, adsorption is thermodynamically spontaneous and exothermic. The chemical bonding of C=O, C–O-related groups in both GO and starch with Cu(II) serves as the main adsorption mechanism. Owing to its high adsorption efficiency, GO/WS may be a promising adsorbent for heavy metal scavenging. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is characterized by amenorrhea and elevated levels of follicle-stimulating hormone (FSH, usually > 25 IU/L) before 40 years of age. To identify the relationship between FSHR mutations and sporadic POI patients of Han Chinese descent, we performed Sanger sequencing of FSHR gene in 192 sporadic POI patients and 192 matched controls of Han Chinese descent. Two heterozygous missense variants, c.793A > G (p.M265V) and c.1789C > A (p.L597I), were identified exclusively in POI patients. Functional studies showed that both mutants were expressed on the cell surface, while p.L597I showed decreased membrane localization compared with wild-type FSHR. Moreover, FSH-induced cAMP production and ERK1/2 phosphorylation were reduced in the cells transfected with p.L597I mutant, but not in the cells transfected with p.M265V mutant. In addition, two single-nucleotide polymorphisms (SNPs), rs1394205 (c.-29G > A) and rs140106399 (c.*111 T > C), were identified in both POI group and control group with significantly different genotypic and allelic distributions. These results indicated that dysfunctional FSHR due to mutation or SNPs might explain a fraction of sporadic POI cases in Han Chinese population. • Etiology of premature ovarian insufficiency is heterogenous. • The signal pathway of follicle stimulation hormone plays a crucial role in follicle development by regulating steroid metabolism. • Two novel missense mutations of follicle stimulation hormone receptor were identified in Chinese sporadic patients with POI. • The p.L597I mutation interrupted FSH-induced cAMP production and ERK1/2 phosphorylation. • Dysfunctional FSHR due to mutation or SNPs might explain a fraction of cases diagnosed with POI in Han Chinese population. Two novel missense mutations of FSHR were identified in Chinese sporadic POI patients, highlighting the contribution of FSHR in the etiology of POI in Han Chinese population. [ABSTRACT FROM AUTHOR]

The front cover picture, provided by Yewen Fang and co‐workers, sheds new light on cyclopropanation. With chloromethyl silicate as a methylene transfer reagent, the alkene cyclopropanation has been accomplished by means of visible light‐mediated redox‐neutral catalysis. This CH2 transfer reaction features broad functional group tolerance and mild conditions. In light of the alkene scope, a great number of Michael acceptors including α,β‐unsaturated phosphonates, acrylates, ketones, amides, and sulfones are suitable substrates under these photocatalytic redox‐neutral conditions. An application of this protocol to the cyclopropanation of an estrone derivative is also presented. Details can be found in the communication on pages 4459–4463 (T. Guo, L, Zhang, X. Liu, Y. Fang, X. Jin, Y. Yang, Y. Li, B. Chen, M. Ouyang, Adv. Synth. Catal. 2018, 360, 4459–4463; DOI: 10.1002/adsc.201800761). [ABSTRACT FROM AUTHOR]

A fluorometric patulin (PAT) assay is presented that is based on the use of magnetic reduced graphene oxide (rGO) and DNase I. The fluorescence of the PAT aptamer labelled with 6-carboxyfluorescein (FAM) is quenched by magnetized reduced graphene oxide (rGO-Fe3O4) due to fluorescence resonance energy transfer (FRET). However, in the presence of PAT, the labelled aptamer is stripped off from rGO-Fe3O4. The rGO-Fe3O4 is then magnetically separated so that the fluorescence of free labelled PAT aptamer is restored. DNase I cannot hydrolyze the aptamer on rGO-Fe3O4, but it can cleave the free aptamer-PAT complex. This will release FAM and PAT which can undergo a number of additional cycles to trigger the cleavage of abundant aptamer. Recycling of DNase I-assisted target therefore leads to a strong amplification of fluorescence and consequently to an assay with low limit of detection. The detection limit for PAT is as low as 0.28 μg L−1 which is about 13 times lower than that without using DNase I. The method offers a new approach towards rapid, sensitive and selective detection based on an aptamer. Conceivably, it has a wide scope in that it may be applied to numerous other analytes if appropriate aptamers are available.Schematic of a fluorometric assay based on the use of magnetic graphene oxide and DNase I. It was applied to the determination of patulin. DNase I was introduced for recycling amplification. The detection limit is about 13 times lower than that without using DNase I. Figure a contains poor quality of text in image. Otherwise, please provide replacement figure file.Thank you. I will provide the figure file. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention. [ABSTRACT FROM AUTHOR]

To solve the problem of low efficiency of manual harvesting of green soybeans and lack of adaptable harvesters, in this study, a brushing-type green soybean harvester was designed. The comb-brushing type green soybean pod harvesting equipment is composed of a front-mounted separation drum, a full-width material delivery mechanism, a negative pressure cleaning system, and a stalk-pod separation system. Based on the operation requirements of the front-mounted brushing-type detachment drum, the drum parameters, parameters of comb arrangement, and structural parameters of the comb, the force analysis in detachment was performed. By taking the pod detachment rate and damage rate as the response indexes, the rotational speed of the drum, the travel speed of the device, and teeth distance as influencing factors, a three-factor five-level orthogonal rotary combination test was carried out by the software Design-Expert. By establishing mathematical regression models for various influencing factors and evaluation indicators, conducting variance analysis and significance analysis on the response indicators of each factor, the optimal parameters were obtained at a rotational speed of teeth of 397.36 rpm/min, minimum axial teeth distance of 4.8 mm and travel speed of the device of 0.5 m/s. Field test results showed that, under the optimal parameter combination, the pod detachment rate was 94%, the damage rate was 3.04%, the harvesting efficiency was greater than 0.187 hm2/h, and impurity content was less than 7.8%, all of which met the design and usage requirements. The research results can provide a reference for the design of soybean harvesters. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Are variants of genes involved in meiosis initiation responsible for premature ovarian insufficiency (POI)? SUMMARY ANSWER A MEIOSIN variant participates in the pathogenesis of human POI by impairing meiosis due to insufficient transcriptional activation of essential meiotic genes. WHAT IS KNOWN ALREADY Meiosis is the key event for the establishment of the ovarian reserve, and several gene defects impairing meiotic homologous recombination have been found to contribute to the pathogenesis of POI. Although STRA8 and MEIOISN variants have been found to associate with POI in a recent study, the condition of other meiosis initiation genes is unknown and direct evidence of variants participating in the pathogenesis of POI is still lacking. STUDY DESIGN, SIZE, DURATION This was a retrospective genetic study. An in-house whole exome sequencing (WES) database of 1030 idiopathic POI patients was screened for variations of meiosis initiation genes. PARTICIPANTS/MATERIALS, SETTING, METHODS Homozygous or compound heterozygous variations of genes involved in meiosis initiation were screened in the in-house WES database. The pathogenicity of the variation was verified by in vitro experiments, including protein structure prediction and dual-luciferase reporter assay. The effect of the variant on ovarian function and meiosis was demonstrated through histological analyses in a point mutation mouse model. MAIN RESULTS AND THE ROLE OF CHANCE One homozygous variant in MEIOSIN (c.1735C>T, p.R579W) and one in STRA8 (c.258 + 1G>A), which initiates meiosis via the retinoic acid-dependent pathway, were identified in a patient with idiopathic POI respectively. The STRA8 variation has been reported in the recently published work. For the MEIOSIN variation, the dual-luciferase reporter assay revealed that the variant adversely affected the transcriptional function of MEIOSIN in upregulating meiotic genes. Furthermore, knock-in mice with the homologous mutation confirmed that the variation impacted the meiotic prophase I program and accelerated oocyte depletion. Moreover, the variant p.R579W localizing in the high-mobility group (HMG) box domain disrupted the nuclear localization of the MEIOSIN protein but was dispensable for the cell-cycle switch of oocytes, suggesting a unique role of the MEIOSIN HMG box domain in meiosis initiation. LIMITATIONS, REASONS FOR CAUTION Further studies are needed to explore the role of other meiosis initiation genes in the pathogenesis of POI. WIDER IMPLICATIONS OF THE FINDINGS The MEIOSIN variant was verified to cause POI by impaired transcriptional regulation of meiotic genes and was inherited by a recessive mode. The function of HMG box domain in MEIOSIN protein was also expanded by this study. Although causative variations in meiotic initiation genes are rare in POI, our study confirmed the pathogenicity of a MEIOSIN variant and elucidated another mechanism of human infertility. STUDY FUNDING/COMPETING INTEREST(s) This work was supported by the National Key Research & Developmental Program of China (2022YFC2703800, 2022YFC2703000), National Natural Science Foundation for Distinguished Young Scholars (82125014), National Natural Science Foundation of China (32070847, 32170867, 82071609), Basic Science Center Program of NSFC (31988101), Natural Science Foundation of Shandong Province for Grand Basic Projects (ZR2021ZD33), Natural Science Foundation of Shandong Province for Excellent Young Scholars (ZR2022YQ69), Taishan Scholars Program for Young Experts of Shandong Province (tsqn202211371), and Qilu Young Scholars Program of Shandong University. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based guidelines? SUMMARY ANSWER A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls. WHAT IS KNOWN ALREADY PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based guidelines. STUDY DESIGN, SIZE, DURATION This cross-sectional case–control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites. MAIN RESULTS AND THE ROLE OF CHANCE We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952). LIMITATIONS, REASONS FOR CAUTION The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based guideline, and it provided new molecular insight into the application of the new guidelines. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Temporal expectation is the ability to select the precise point in time for doing something to produce an optimal effect. Two sources of information that humans use to generate temporal expectations are rhythmic and symbolic cues. Both types of cues have been proven effective in directing attention to a future point in time resulting in improved performance. However, the temporal precision of the two forms of temporal expectation have rarely been compared. In the current study, 17 participants performed two temporal expectation tasks in which either a rhythmic cue or a symbolic cue indicated that a future target would appear after a 500-ms (short) or 1,500-ms (long) interval; the target appeared at the expected time in 54% of trials and at an unexpected earlier or later interval in 36% of trials. In both tasks, we observed that the reaction time (RT) curves were U-shaped, with a slower RT for the earlier and later unexpected intervals and a faster RT for intervals approaching the expected point in time. Furthermore, we found a significant interaction between task and the quadratic term of temporal expectation, which indicates that the U-shaped RT curves for the rhythmic cue task are steeper than those for the symbolic cue task. Thus, the current results revealed that compared with symbolic cues, temporal expectation driven by rhythmic cues provides a more precise attentional focus in time. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a large group of disorders, most of which lead to progressive scarring of lung tissue. The scarring associated with ILD eventually affects your ability to breathe and get enough oxygen into your bloodstream. The typical symptoms of ILD are shortness of breath at rest or aggravated by exertion and dry cough. In this study, we enrolled a family with ILDs from central south region of China. Three patients suffered from repeated cough and shortness of breath. The high resolution computed tomography (HRCT) testing further confirmed the diagnosis of interstitial lung lesions. Whole exome sequencing (WES) and Sanger sequencing were applied to detect the genetic lesion of the family. By employing WES, a novel heterozygous mutation (NM_001098668: c.554C>T/p.A185V) of surfactant protein A2 (SFTPA2) was identified in the affected individuals and absent in the healthy members. Bioinformatics analysis predicted that this mutation is disease-causing mutation and located in an evolutionarily conserved site of SFTPA2 protein. The novel mutation may disrupt the stability of SFTPA2 protein and induce endoplasmic reticulum stress, finally leading to ILD under the influence of microorganisms. Our study not only expands the spectrum of SFTPA2 mutations but also helps the family members to mitigate ILD risk factors. The study also supplements and improves genetic testing strategies and ILD risk estimation methodologies for China. [ABSTRACT FROM AUTHOR]

Clostridium scatologenes ATCC 25775 T is an acetogenic anaerobic bacteria known to be capable of synthesizing volatile fatty acids and solvents from CO 2 or CO on its autotrophic mode and producing 3-methylindole and 4-methylphenol on its heterotrophic mode. Here, we report the complete genome sequence of this strain, which might provide a lot of valuable information for developing metabolic engineering strategies to produce biofuels or chemicals from greenhouse gases. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a serious disorder with a high mortality rate worldwide. It is characterized by irreversible scarring of the lung parenchyma resulting from excessive collagen production by proliferating fibroblasts/myofibroblasts. Previous studies have revealed that mutations in surfactant protein‐related genes and telomerase complex genes are crucial underlying genetic factors. Methods: In this study, we enrolled a family with IPF from the central southern region of China. Whole‐exome sequencing was employed to explore candidate genes in this family. Real‐time PCR and western blotting were used to study the functions of the identified mutations in vitro. Results: A novel mutation (NM_001098668.4: c.619A>T; NP_001092138.1: p.N207Y) in surfactant protein A2 (SFTPA2,), having not been previously reported to be a mutation, was identified and co‐separated with all affected individuals in the IPF family. Functional research further revealed that the novel mutation affects the secretion of SFTPA2 protein and induces endoplasmic reticulum stress as well as apoptosis in A549 cells. Conclusion: We are confident that this novel mutation (NM_001098668.4: c.619A>T; NP_001092138.1: p.N207Y) in SFTPA2 is the genetic mutation of the IPF family. Our study not only confirms the importance of SFTPA2 in IPF but also expands the spectrum of SFTPA2 mutations and contributes to the genetic diagnosis and counseling of IPF patients. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3) infection causes many inflammation-related diseases, such as viral myocarditis and aseptic meningitis. However, no vaccines or drugs have been approved for prevention or therapy of CVB3-induced diseases. In this study, luteolin (3,4,5,7-tetrahydroxyflavone) had been found that could dose-dependently reduce the production of viral progeny and synthesis of CVB3 RNA and protein. The luteolin-mediated inhibition of CVB3 was found to be mechanistically possible, at least in part, through depressing the phosphorylation of p38 MAPK and JNK MAPK, and inhibiting NF-κB nuclear translocation and subsequently attenuated the expression of inflammatory cytokines in CVB3-infected cells. Luteolin may be a potential agent or supplement against CVB3 infection by inhibiting inflammation. [ABSTRACT FROM AUTHOR]