VEGF-B is involved in diabetic peripheral neuropathy in patients with type 2 diabetes.

Aims: This study aims to explore the potential role of vascular endothelial growth factor-B (VEGF-B) in the pathogenesis of diabetic peripheral neuropathy (DPN). The expression of VEGFRs were reanalysed by using gene arrays of peripheral nerve samples from mouse models of DPN retrieved from the GEO database. 213 T2D patients as well as 31 healthy individuals were recruited. The serum VEGF-B was detected and its relationship with DPN was analysed. The elevated VEGFR1 was the only change of VEGFR gene expression in the peripheral nerve from mouse models of DPN. The level of serum VEGF-B in T2D patients with DPN was higher than that in T2D patients without DPN and healthy people. Analysis of correlation and binary logistic regression confirmed that the increased serum VEGF-B level was an independent risk factor of DPN in T2D patients. VEGF-B-VEGFR1 signaling pathway may be involved in the development of DPN.

Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

Efficacy and safety of diacerein monotherapy in adults with obesity: A randomized, double-blind, placebo-controlled trial.

AIM: To assess the efficacy and safety of diacerein monotherapy in adults with obesity. METHODS: Forty-two adults with obesity participated in the study and were randomly assigned to receive diacerein or placebo in addition to lifestyle modification for 14 weeks, in a double-blinded fashion. Differences in changes in body weight, body composition, metabolic variables, fatty liver-related indicators, cardiovascular system variables, lifestyle score and metabolic factors were compared. RESULTS: Post-treatment weight loss percentage from baseline was -6.56% (-8.71%, -4.41%) in the diacerein group and -0.59% (-2.74%, 1.56%) in the placebo group. Compared with the placebo group, the diacerein group showed significant improvements in body composition, metabolic variables and indicators related to fatty liver. In addition, after 14 weeks of treatment, diacerein led to a significant reduction in serum visfatin concentration versus the placebo group. The reductions in total body fat mass and visceral fat area mediated the weight loss induced by diacerein. No significant differences were found between the groups in the number of adverse events and safety variables. CONCLUSIONS: For adults with obesity, diacerein led to a clinically meaningful weight loss and provided multiple metabolic benefits with acceptable safety. These results support that diacerein is a promising candidate medicine to be developed for obesity management.

AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression in Toxoplasma gondii.

Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to two primary ApiAP2s (AP2XII-1 and AP2XI-2), demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of AP2XII-1 and AP2XI-2 resulted in a profound alteration in merozoite-specific genes targeted by the MORC-HDAC3 complex. Additionally, considerable overlap was observed in downstream gene profiles between AP2XII-1 and AP2XI-2, with AP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including AP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by AP2XII-1 and AP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.

Transcriptomic analysis reveals that Bacillomycin D-C16 induces multiple pathways of disease resistance in cherry tomato.

BACKGROUND: Bacillomycin D-C16 can induce resistance in cherry tomato against pathogens; however, the underlying molecular mechanism is poorly understood. Here, the effect of Bacillomycin D-C16 on induction of disease resistance in cherry tomato was investigated using a transcriptomic analysis. RESULTS: Transcriptomic analysis revealed a series of obvious enrichment pathways. Bacillomycin D-C16 induced phenylpropanoid biosynthesis pathways and activated the synthesis of defense-related metabolites including phenolic acids and lignin. Moreover, Bacillomycin D-C16 triggered a defense response through both hormone signal transduction and plant-pathogen interactions pathways, and increased the transcription of several transcription factors (e.g., AP2/ERF, WRKY and MYB). These transcription factors might contribute to the further activated the expression of defense-related genes (PR1, PR10 and CHI) and stimulated the accumulation of H2O2. CONCLUSION: Bacillomycin D-C16 can induce resistance in cherry tomato by activating the phenylpropanoid biosynthesis pathway, hormone signal transduction pathway and plant-pathogen interactions pathway, thus activating comprehensive defense reaction against pathogen invasion. These results provided a new insight into the bio-preservation of cherry tomato by the Bacillomycin D-C16.

PddCas: A Polydisperse Droplet Digital CRISPR/Cas-Based Assay for the Rapid and Ultrasensitive Amplification-Free Detection of Viral DNA/RNA.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based assays have been an emerging diagnostic technology for pathogen diagnosis. In this work, we developed a polydisperse droplet digital CRISPR-Cas-based assay (PddCas) for the rapid and ultrasensitive amplification-free detection of viral DNA/RNA with minimum instruments. LbaCas12a and LbuCas13a were used for the direct detection of viral DNA and RNA, respectively. The reaction mixtures were partitioned with a common vortex mixer to generate picoliter-scale polydisperse droplets in several seconds. The limit of detection (LoD) for the target DNA and RNA is approximately 100 aM and 10 aM, respectively, which is about 3 × 104-105 fold more sensitive than corresponding bulk CRISPR assays. We applied the PddCas to successfully detect severe acute respiratory syndrome coronavirus (SARS-CoV-2) and human papillomavirus type 18 (HPV 18) in clinical samples. For the 23 HPV 18-suspected cervical epithelial cell samples and 32 nasopharyngeal swabs for SARS-CoV-2, 100% sensitivity and 100% specificity were demonstrated. The dual-gene virus detection with PddCas was also established and verified. Therefore, PddCas has potential for point-of-care application and is envisioned to be readily deployed for frequent testing as part of an integrated public health surveillance program.

Facile Synthesis and Multiple Application of Ultralong-Afterglow Room Temperature Phosphorescence Aggregate Carbon Dots from Simple Raw Materials.

Owing to the ultralong afterglow, room temperature decay phosphorescence nanomaterials have aroused enough attention. In the work, by simple one-pot solid-state thermal decomposition reaction, aggregate carbon dots (CDs) was prepared from trimesic and boric acid. Based on the intermolecular hydrogen bonds and intramolecular π-π stacking weak interaction from precursors, CDs was encapsulated in boron oxide matrix and formed aggregation. The aggregate state of CDs facilitated the triplet excited states (Tn), which could induce the room temperature decay phosphorescence properties. By careful investigation, under different excitation wavelengths at 254 and 365 nm, the aggregate CDs showed > 15 s and > 3 s room temperature phosphorescence emission in the naked eye, which was associated with 1516.12 ms and 718.62 ms lifetime respectively. And the aggregate CDs exhibited widespread application in encoding encryption, optical anti-counterfeiting and fingerprint identification etc. The interesting aggregate CDs revealed unexpected ultralong-afterglow room temperature decay phosphorescence properties and the work opened a window for constructing ultralong-afterglow room temperature decay phosphorescence aggregate CDs nanomaterials.

The moderating effect of resting heart rate variability on the relationship between internet addiction tendency and brain morphology.

Previous neuroimaging studies have investigated brain morphology associated with internet addiction tendency (IAT) in healthy subjects. However, whether resting vagally-mediated heart rate variability (HRV) exerting influences on the association of IAT and brain morphology remains unclear. This study used voxel-based morphometry (VBM) and multiple regression analyses to assess the interaction effect of IAT and resting vagally-mediated HRV on regional grey matter volumes in 82 healthy subjects. To further illustrate the observed interaction effect, the moderated hierarchical regression analysis was performed. The results showed that resting vagally-mediated HRV moderated the relationship between IAT scores and grey matter volume (GMV) in the precuneus and cerebellum. Specifically, individuals with higher resting vagally-mediated HRV showed a significant positive relationship between IAT scores and GMV in the precuneus, whereas individuals with lower resting vagally-mediated HRV showed a significant negative relationship between IAT scores and GMV in the precuneus. In addition, IAT scores were negatively correlated with GMV in the cerebellum among individuals with lower resting vagally-mediated HRV, but not among individuals with higher resting vagally-mediated HRV. These findings have demonstrated a moderating role of resting vagally-mediated HRV on the association of IAT and brain morphology.

De-Linker-Enabled Exceptional Volumetric Acetylene Storage Capacity and Benchmark C2 H2 /C2 H4 and C2 H2 /CO2 Separations in Metal-Organic Frameworks.

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

Microbial production of the plant-derived fungicide physcion.

Physcion is a characteristic component of the traditional herb rhubarb with diverse pharmacological activities that has been commercially approved as an herbal fungicide. Nevertheless, its extremely low contents, costly purification procedure and geographically restricted planting severely hinder its application. Here, a cell factory was constructed in the filamentous fungus Aspergillus terreus for physcion production via microbial fermentation by integrating a pathway-modified emodin accumulation module and a position-selective emodin methylation module. Specifically, 1.71 g/L emodin accumulated when the transcriptional activator GedR and the emodin-1-OH-O-methyltransferase GedA in the geodin biosynthetic pathway were overexpressed and knocked out, respectively. Subsequently, potential emodin-3-OH-O-methyltransferase candidates were enzymatically screened in vitro and introduced into the emodin-accumulating mutant in vivo to generate a physcion-producing strain showing the highest titre of 6.3 g/L in fed-batch fermentation. Thus, our study provides an alternative strategy for the highly efficient, economical production of physcion and a representative example for microbial synthetic biology.

Copper-promoted difunctionalization of unactivated alkenes with silanes.

An efficient copper-catalyzed cascade difunctionalization of N-allyl anilines toward the synthesis of silylated indolines using commercially available silanes has been reported. This strategy provides a new avenue for the synthesis of a diverse array of indolines in reasonable yields. Preliminary mechanistic investigations indicate that the reaction probably proceeds via a radical pathway with unactivated alkenes as radical acceptors and simple silanes as radical precursors. This protocol is distinguished by its atom economy, broad substrate scope and readily available starting materials.

Liquid crystal microlens array with positive and negative focal lengths based on a patterned electrode.

A liquid crystal microlens array (LCMLA) with positive and negative focal lengths based on a ring-array patterned electrodes is demonstrated. By carefully designing patterned electrodes with a circular electrode array area and outer ring electrode region area, the switching of the positive and negative lens effect can be easily achieved in a single cell. A positive lens effect appeared when the voltage was applied to the outer ring electrode region and the top substrate. The focal length changed from infinity to 1 mm as the voltage varied from 0 to 3Vrms. A negative lens effect occurred when the voltage was applied to the circular electrode array and the top substrate. The focal length varied from infinity to -1mm when the voltage changed from 0 to 2Vrms. The imaging properties of the LCMLA at different voltages are evaluated. Our LCMLA, with simple structure, low driving voltage, and good stability, has potential applications in optical communication, imaging processing, and displays.

Comparison of the biometric parameters in patients with high myopia and anisometropia.

BACKGROUND: To compare biometric parameters, especially lens parameters, in patients with high myopia and anisometropia. METHODS: Patients with spherical equivalent greater than -6D and at least one eye with an axial length greater than 26 mm and a difference in binocular axial length greater than 2 mm were included in this study. In each patient, the eye with a relatively shorter axial length was assigned to Group S, and the other eye was assigned to Group L. In patients whose binocular axial length difference was greater than 4 mm, the eye with the shorter axial length was assigned to Group S1 and the other eye was assigned to Group L1. In patients whose shorter eye axial was less than 26 mm, the eye with the shorter axial was assigned to Group S2 and the other eye was assigned to Group L2. Central corneal thickness, corneal curvature radius, axial length, anterior chamber depth, lens thickness, white-to-white corneal diameter and the radius of the anterior and posterior lens capsules were compared between Group S and Group L, Groups S1 and L1, and Groups S2 and L2. RESULTS: Sixty-four people were enrolled in the study. There were 26 people with an axial length difference more than 4 mm (Group S1 and Group L1) and 34 patients with an axial length less than 26 mm (Group S2 and Group L2). No significant differences were found in any parameters except axial length between Group S and Group L, Groups S1 and L1, or Groups S2 and L2 (p > 0.05). CONCLUSIONS: The anterior parameters of patients with high myopia did not change with the axial length.

Bienzyme-Catalytic and Dioxygenation-Mediated Anthraquinone Ring Opening.

The C-10-C-4a bond cleavage of anthraquinone is believed to be a crucial step in fungal seco-anthraquinone biosynthesis and has long been proposed as a classic Baeyer-Villiger oxidation. Nonetheless, genetic, enzymatic, and chemical information on ring opening remains elusive. Here, a revised questin ring-opening mechanism was elucidated by in vivo gene disruption, in vitro enzymatic analysis, and 18O chasing experiments. It has been confirmed that the reductase GedF is responsible for the reduction of the keto group at C-10 in questin to a hydroxyl group with the aid of NADPH. The C-10-C-4a bond of the resultant questin hydroquinone is subsequently cleaved by the atypical cofactor-free dioxygenase GedK, giving rise to desmethylsulochrin. This proposed bienzyme-catalytic and dioxygenation-mediated anthraquinone ring-opening reaction shows universality.

Tunable multi-mode laser based on robust cholesteric liquid crystal microdroplet.

To date, various studies have been dedicated to the development of cholesteric liquid crystal (CLC) microdroplet omnidirectional lasers. In this work, a stable and tunable multi-mode laser emission is achieved by designing a dye-doping CLC microdroplet. In such a structure, the polymer network only exists on the surface, maintaining stability while providing tunability, and due to the uneven distribution of the pitch, it leads to multi-mode laser emission. A large number of microdroplets are produced quickly via a new method based on ultrasonic separation. During the reaction, we introduce interfacial polymerization where monomers and photoinitiator are respectively distributed inside and outside the microdroplets through mutual diffusion, which enables one to make the polymer network exist on the surface instead of the interior. The obtained microdroplet-based multi-mode laser is shown to possess stability and tunability, demonstrating a great potential for flexible devices and 3D displays.

Optimizing the performance of digital loop-mediated isothermal amplification.

Digital loop-mediated isothermal amplification (dLAMP) is attractive for the detection of nucleic acid due to its superior characteristics including isothermal amplification, absolute quantification, and single-molecule sensitivity. However, dLAMP suffers from the inaccurate quantification caused by low digital efficiency, which means only part of loaded template molecules could be amplified. We here developed a prehybridization-induced enhancement (PIE) strategy which could improve digital efficiency about 2-40 times without any new primer or additional operation. This work provides new insight into understanding the reaction dynamic of dLAMP. The PIE strategy could be applied to the other digital amplification methods.

Amide-Functionalized Metal-Organic Frameworks Coupled with Open Fe/Sc Sites for Efficient Acetylene Purification.

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

Sensitive and rapid on-site detection of SARS-CoV-2 using a gold nanoparticle-based high-throughput platform coupled with CRISPR/Cas12-assisted RT-LAMP.

The outbreak of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic. The high infectivity of SARS-CoV-2 highlights the need for sensitive, rapid and on-site diagnostic assays of SARS-CoV-2 with high-throughput testing capability for large-scale population screening. The current detection methods in clinical application need to operate in centralized labs. Though some on-site detection methods have been developed, few tests could be performed for high-throughput analysis. We here developed a gold nanoparticle-based visual assay that combines with CRISPR/Cas12a-assisted RT-LAMP, which is called Cas12a-assisted RT-LAMP/AuNP (CLAP) assay for rapid and sensitive detection of SARS-CoV-2. In optimal condition, we could detect down to 4 copies/µL of SARS-CoV-2 RNA in 40 min. by naked eye. The sequence-specific recognition character of CRISPR/Cas12a enables CLAP a superior specificity. More importantly, the CLAP is easy for operation that can be extended to high-throughput test by using a common microplate reader. The CLAP assay holds a great potential to be applied in airports, railway stations, or low-resource settings for screening of suspected people. To the best of our knowledge, this is the first AuNP-based colorimetric assay coupled with Cas12 and RT-LAMP for on-site diagnosis of COVID-19. We expect CLAP assay will improve the current COVID-19 screening efforts, and make contribution for control and mitigation of the pandemic.

Precise Pore Space Partitions Combined with High-Density Hydrogen-Bonding Acceptors within Metal-Organic Frameworks for Highly Efficient Acetylene Storage and Separation.

The high storage capacity versus high selectivity trade-off barrier presents a daunting challenge to practical application as an acetylene (C2 H2 ) adsorbent. A structure-performance relationship screening for sixty-two high-performance metal-organic framework adsorbents reveals that a moderate pore size distribution around 5.0-7.5 Šis critical to fulfill this task. A precise pore space partition approach was involved to partition 1D hexagonal channels of typical MIL-88 architecture into finite segments with pore sizes varying from 4.5 Š(SNNU-26) to 6.4 Š(SNNU-27), 7.1 Š(SNNU-28), and 8.1 Š(SNNU-29). Coupled with bare tetrazole N sites (6 or 12 bare N sites within one cage) as high-density H-bonding acceptors for C2 H2 , the target MOFs offer a good combination of high C2 H2 /CO2 adsorption selectivity and high C2 H2 uptake capacity in addition to good stability. The optimized SNNU-27-Fe material demonstrates a C2 H2 uptake of 182.4 cm3 g-1 and an extraordinary C2 H2 /CO2 dynamic breakthrough time up to 91 min g-1 under ambient conditions.

Redox-Responsive Transcription Factor 1 (RRFT1) Is Involved in Extracellular ATP-Regulated Arabidopsis thaliana Seedling Growth.

Extracellular adenosine triphosphate (eATP) is an apoplastic signaling molecule that plays an essential role in the growth and development of plants. Arabidopsis seedlings have been reported to respond to eATP; however, the downstream signaling components are still not well understood. In this study, we report that an ethylene-responsive factor, Redox-Responsive Transcription Factor 1 (RRTF1), is involved in eATP-regulated Arabidopsis thaliana seedling growth. Exogenous adenosine triphosphate inhibited green seedling root growth and induced hypocotyl bending of etiolated seedlings. RRTF1 loss-of-function mutant (rrtf1) seedlings showed decreased responses to eATP, while its complementation or overexpression led to recovered or increased eATP responsiveness. RRTF1 was expressed rapidly after eATP stimulation and then migrated into the nuclei of root tip cells. eATP-induced auxin accumulation in root tip or hypocotyl cells was impaired in rrtf1. Chromatin immunoprecipitation and high-throughput sequencing results indicated that eATP induced some genes related to cell growth and development in wild type but not in rrtf1 cells. These results suggest that RRTF1 may be involved in eATP signaling by regulating functional gene expression and cell metabolism in Arabidopsis seedlings.