Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases.

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which's an important synthetic intermediate of antifungal drug Ravuconazole.

Genome-scale identification, expression and evolution analysis of B-box members in Dendrobium huoshanense.

B-box (BBX) proteins have been recognized as vital determinants in plant development, morphogenesis, and adaptive responses to a myriad of environmental stresses. These zinc-finger proteins play a pivotal role in various biological processes. Their influence spans photomorphogenesis, the regulation of flowering, and imparting resilience to a wide array of challenges, encompassing both biotic and abiotic factors. Chromosome localization, gene structure and conserved motifs, phylogenetic analysis, collinearity analysis, expression profiling, fluorescence quantitative analysis, and tobacco transient transformation methods were used for functional localization and expression pattern analysis of the DhBBX gene. A total of 23 DhBBX members were identified from Dendrobium huoshanense. Subsequent phylogenetic evaluations effectively segregated these genes into five discrete evolutionary subsets. The predictions of subcellular localizations revealed that all these proteins were localized in the nucleus. The genetic composition and patterns showed that the majority of these genes consisted of several exons, with a few variations that could be attributed to transposon insertion. A comprehensive analysis using qRT-PCR was conducted to unravel the expression patterns of these genes in D. huoshanense, with a specific concentration on their responses to various hormone treatments and cold stress. Subcellular localization reveals that DhBBX21 and DhBBX9 are located in the nucleus. Our results provide a deep comprehension of the complex regulatory mechanisms of BBXs in response to various environmental and hormonal stimuli. These discoveries encourage further detailed and focused investigations into the operational dynamics of the BBX gene family in a wider range of plant species.

Ganoderic acid a decreased Aß42-induced neurotoxicity in PC12 cells by reduced mitochondrial damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Accumulation of ß-amyloid (Aß) in the brain has been recognized as a key factor in the onset and progression of Alzheimer's disease (AD).The accumulation of Aß in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aß42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aß42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aß42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aß protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer's disease.

Comparative metabolic profiling of the mycelium and fermentation broth of Penicillium restrictum from Peucedanum praeruptorum rhizosphere.

Microorganisms in the rhizosphere, particularly arbuscular mycorrhiza, have a broad symbiotic relationship with their host plants. One of the major fungi isolated from the rhizosphere of Peucedanum praeruptorum is Penicillium restrictum. The relationship between the metabolites of P. restrictum and the root exudates of P. praeruptorum is being investigated. The accumulation of metabolites in the mycelium and fermentation broth of P. restrictum was analysed over different fermentation periods. Non-targeted metabolomics was used to compare the differences in intracellular and extracellular metabolites over six periods. There were significant differences in the content and types of mycelial metabolites during the incubation. Marmesin, an important intermediate in the biosynthesis of coumarins, was found in the highest amount on the fourth day of incubation. The differential metabolites were screened to obtain 799 intracellular and 468 extracellular differential metabolites. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the highly enriched extracellular metabolic pathways were alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, and terpenoid backbone biosynthesis. In addition, the enrichment analysis associated with intracellular and extracellular ATP-binding cassette transporter proteins revealed that some ATP-binding cassette transporters may be involved in the transportation of certain amino acids and carbohydrates. Our results provide some theoretical basis for the regulatory mechanisms between the rhizosphere and the host plant and pave the way for the heterologous production of furanocoumarin.

Facial Video-Based Non-Contact Stress Recognition Utilizing Multi-Task Learning With Peak Attention.

Negative emotional states, such as anxiety and depression, pose significant challenges in contemporary society, often stemming from the stress encountered in daily activities. Stress (state or level) recognition is a crucial prerequisite for effective stress management and intervention. Presently, wearable devices have been employed to capture physiological signals and analyze stress states. However, their constant skin contact can lead to discomfort and disturbance during prolonged monitoring. In this paper, a peak attention-based multitasking framework is presented for non-contact stress recognition. The framework extracts rPPG signals from RGB facial videos, utilizing them as inputs for a novel multi-task attentional convolutional neural network for stress recognition (MTASR). It incorporates peak detection and HR estimation as auxiliary tasks to facilitate stress recognition. By leveraging multi-task learning, MTASR can utilize information related to stress physiological responses, thereby enhancing feature extraction efficiency. For stress recognition, two binary classification tasks are applied: stress state recognition and stress level recognition. The model is validated on the UBFC-Phys public dataset and demonstrates an accuracy of 94.33% for stress state recognition and 83.83% for stress level recognition. The proposed method outperforms the dataset's baseline methods and other competing approaches.

Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

Recognition on pharmacodynamic ingredients of natural products.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

Effectiveness and safety of Governor vessel acupuncture therapy for post-stroke cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of Governor vessel acupuncture (GV Ac) in treating post-stroke cognitive impairment (PSCI). METHODS: There was a total of seven databases examined. Four English databases (Cochrane Library, PubMed, Embase, and Medline) and three Chinese databases (Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Databases (VIP), and Wan Fang Database) contain all randomized controlled trials (RCTs) comparing Governor vessel acupuncture to other treatments or none acupuncture for PSCI. The exact dates for the search period are from January 1, 2000, to January 1, 2023.Two researchers independently reviewed the literature, gathered RCT data, and performed statistical analysis. All data were analyzed using Review Manager software (Rev Man) 5.3. RESULTS: This meta-analysis includes a total of 39 trials with 2044 patients. There were 1022 participants in each of the test and control groups. Following 12-120 days of acupuncture treatment, a meta-analysis revealed that the treatment groups (GV Ac combined with conventional treatment groups) significantly increased their scores on the Curative ratio (OR = 3.00, 95 %CI = 2.37-3.79, P = 0.98, I² = 0 %), Montreal Cognitive Assessment (MoCA)(MD = 1.82, 95 %CI = 1.60-2.03, P = 0.11, I² = 25 %), Mini-Mental State Examination (MMSE)(MD = 2.18, 95 %CI = 1.64-2.72, P<0.005, I² = 92 %), and Activity of Daily Living (ADL)(MD = 5.99, 95 %CI = 5.33-6.64, P = 0.19, I² = 26 %). CONCLUSION: The results suggested that acupuncture on points of the Governor vessel enhanced cognitive function in stroke survivors.

Assessing the relationship between levator palpebrae superioris and thyroid-associated ophthalmopathy using the Dixon-T2WI sequence.

Background: The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI. Methods: The retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS_T) and signal intensity ratio (LPS_SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS_T and LPS_SIR. Results: In the TAO group, LPS_T and LPS_SIR were higher than those in the normal group (p < 2.2e-16). The upper lid retraction (ULR) ≥ 2 mm group exhibited higher LPS_T and LPS_SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS_T (cutoff: 1.505 mm) and 0.81 for LPS_SIR (cutoff: 1.170). LPS_T (p = 2.8e-07) and LPS_SIR (p = 3.9e-12) in the active phase were higher than in the inactive phase. LPS_T and LPS_SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups (p < 0.05). ROC showed an AUC of 0.70 for LPS_T (cutoff: 2.095 mm) in judging the active phase, and 0.78 for LPS_SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS_T (cutoff: 2.095 mm) and 0.78 for LPS_SIR (cutoff: 1.197). Conclusion: The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO.

Identification of Dof transcription factors in Dendrobium huoshanense and expression pattern under abiotic stresses.

Introduction: DNA-binding with one finger (Dof) transcription factors (TFs) are a unique family of TFs found in higher plants that regulate plant responses to light, hormones, and abiotic stresses. The specific involvement of Dof genes in the response to environmental stresses remains unknown in D. huoshanense. Methods: A total of 22 Dof family genes were identified from the D. huoshanense genome. Results: Chromosome location analysis showed that DhDof genes were distributed on 12 chromosomes, with the largest number of Dof genes located on chromosome 8. The phylogenetic tree revealed that DhDofs could be categorized into 11 distinct subgroups. In addition to the common groups, DhDof4, DhDof5, DhDof17, and the AtDof1.4 ortholog were clustered into the B3 subgroup. Group E was a newly identified branch, among which DhDof6, DhDof7, DhDof8, and DhDof9 were in an independent branch. The conserved motifs and gene structure revealed the differences in motif number and composition of DhDofs. The dof domain near the N-terminus was highly conserved and contained a C2-C2-type zinc finger structure linked with four cysteines. Microsynteny and interspecies collinearity revealed gene duplication events and phylogenetic tree among DhDofs. Large-scale gene duplication had not occurred among the DhDofs genes and only in one pair of genes on chromosome 13. Synteny blocks were found more often between D. huoshanense and its relatives and less often between Oryza sativa and Arabidopsis thaliana. Selection pressure analysis indicated that DhDof genes were subject to purifying selection. Expression profiles and correlation analyses revealed that the Dof gene under hormone treatments showed several different expression patterns. DhDof20 and DhDof21 had the highest expression levels and were co-expressed under MeJA induction. The cis-acting element analysis revealed that each DhDof had several regulatory elements involved in plant growth as well as abiotic stresses. qRT-PCR analysis demonstrated that DhDof2 was the main ABA-responsive gene and DhDof7 was the main cold stress-related gene. IAA suppressed the expression of some Dof candidates, and SA inhibited most of the candidate genes. Discussion: Our results may provide new insights for the further investigation of the Dof genes and the screening of the core stress-resistance genes.

N-type semiconducting hydrogel.

Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.

Comparative analysis of POD genes and their expression under multiple hormones in Pyrus bretschenedri.

BACKGROUND: Class III peroxidase (POD) enzymes play vital roles in plant development, hormone signaling, and stress responses. Despite extensive research on POD families in various plant species, the knowledge regarding the POD family in Chinese pear (Pyrus bretschenedri) is notably limited. RESULTS: We systematically characterized 113 POD family genes, designated as PbPOD1 to PbPOD113 based on their chromosomal locations. Phylogenetic analysis categorized these genes into seven distinct subfamilies (I to VII). The segmental duplication events were identified as a prevalent mechanism driving the expansion of the POD gene family. Microsynteny analysis, involving comparisons with Pyrus bretschenedri, Fragaria vesca, Prunus avium, Prunus mume and Prunus persica, highlighted the conservation of duplicated POD regions and their persistence through purifying selection during the evolutionary process. The expression patterns of PbPOD genes were performed across various plant organs and diverse fruit development stages using transcriptomic data. Furthermore, we identified stress-related cis-acting elements within the promoters of PbPOD genes, underscoring their involvement in hormonal and environmental stress responses. Notably, qRT-PCR analyses revealed distinctive expression patterns of PbPOD genes in response to melatonin (MEL), salicylic acid (SA), abscisic acid (ABA), and methyl jasmonate (MeJA), reflecting their responsiveness to abiotic stress and their role in fruit growth and development. CONCLUSIONS: In this study, we investigated the potential functions and evolutionary dynamics of PbPOD genes in Pyrus bretschenedri, positioning them as promising candidates for further research and valuable indicators for enhancing fruit quality through molecular breeding strategies.

Antiferromagnetic magnonic charge current generation via ultrafast optical excitation.

Néel spin-orbit torque allows a charge current pulse to efficiently manipulate the Néel vector in antiferromagnets, which offers a unique opportunity for ultrahigh density information storage with high speed. However, the reciprocal process of Néel spin-orbit torque, the generation of ultrafast charge current in antiferromagnets has not been demonstrated. Here, we show the experimental observation of charge current generation in antiferromagnetic metallic Mn2Au thin films using ultrafast optical excitation. The ultrafast laser pulse excites antiferromagnetic magnons, resulting in instantaneous non-equilibrium spin polarization at the antiferromagnetic spin sublattices with broken spatial symmetry. Then the charge current is generated directly via spin-orbit fields at the two sublattices, which is termed as the reciprocal phenomenon of Néel spin-orbit torque, and the associated THz emission can be detected at room temperature. Besides the fundamental significance on the Onsager reciprocity, the observed magnonic charge current generation in antiferromagnet would advance the development of antiferromagnetic THz emitter.

Evaluation of an E6/E7 PCR-capillary electrophoresis fragment analysis in the genotyping of human papillomavirus in archival FFPE samples of oropharyngeal cancer.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

Genome-wide identification and expression analysis of TIFY genes under MeJA, cold and PEG-induced drought stress treatment in Dendrobium huoshanense.

The TIFY family consists of plant-specific genes that regulates multiple plant functions, including developmental and defense responses. Here, we performed a comprehensive genomic analysis of TIFY genes in Dendrobium huoshanense. Our analysis encompassed their phylogenetic relationships, gene structures, chromosomal distributions, promoter regions, and patterns of collinearity. A total of 16 DhTIFY genes were identified, and classified into distinct clusters named JAZ, PPD, ZIM, and TIFY based on their phylogenetic relationship. These DhTIFYs exhibited an uneven distribution across 7 chromosomes. The expansion of the DhTIFY gene family appears to have been significantly influenced by whole-genome and segmental duplication events. The ratio of non-synonymous to synonymous substitutions (Ka/Ks) implies that the purifying selection has been predominant, maintaining a constrained functional diversification after duplication events. Gene structure analysis indicated that DhTIFYs exhibited significant structural variation, particularly in terms of gene organization and intron numbers. Moreover, numerous cis-acting elements related to hormone signaling, developmental processes, and stress responses were identified within the promoter regions. Subsequently, qRT-PCR experiments demonstrated that the expression of DhTIFYs is modulated in response to MeJA (Methyl jasmonate), cold, and drought treatment. Collectively, these results enhance our understanding of the functional dynamics of TIFY genes in D. huoshanense and may pinpoint potential candidates for detailed examination of the biological roles of TIFY genes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01442-9.

Diversity and ecological assembly process of aerobic anoxygenic phototrophic bacteria in a low irradiation area, Three Gorges Reservoir.

Aerobic anoxygenic phototrophic bacteria (AAPB) are significant bacterial groups in aquatic ecosystems, known for their rapid growth and photoheterotrophic characteristics. However, the distribution and ecological assembly process of AAPB in low irradiation freshwater basins remain unclear, warranting further investigation. In this study, we present the diversity, abundance, spatial variations, ecological process, and community interaction of AAPB in sediment of Three Gorges Reservoir (TGR) under low irradiation. Our findings demonstrate the dominant genera of AAPB community that exist in the TGR area also are appeared in different waters, with some regional preference. Moreover, the concentration of pufM gene, an indicator for AAPB, maintains a consistently high numerical level ranging from (2.21 ± 0.44) × 104 to (9.98 ± 0.30) × 107 gene copies/g. Although solar irradiation is suggested as the major factor affecting AAPB, it remains unclear whether and how AAPB differ between regions due to varying solar irradiation levels. Our results show spatial differences between total bacteria and AAPB communities, with significant differences observed only in AAPB. Geographical and environmental factor contributed less than 10% to the spatial difference of community, with sediment type and environmental factors being the key factors influencing microbial community structure. The stochastic process plays a dominant role in the aggregation and replacement of AAPB communities, among which the most contribution is dispersal limitation. For AAPB network, Yoonia and Gemmobacter are the hubs for modules. Those results valuable insights into the AAPB communities in TGR with low irradiation.

Experimental observation of current-driven antiskyrmion sliding in stripe domains.

Magnetic skyrmions are promising as next-generation information units. Their antiparticle-the antiskyrmion-has also been discovered in chiral magnets. Here we experimentally demonstrate antiskyrmion sliding in response to a pulsed electric current at room temperature without the requirement of an external magnetic field. This is realized by embedding antiskyrmions in helical stripe domains, which naturally provide one-dimensional straight tracks along which antiskyrmion sliding can be easily launched with low current density and without transverse deflection from the antiskyrmion Hall effect. The higher mobility of the antiskyrmions in the background of helical stripes in contrast to the typical ferromagnetic state is a result of intrinsic material parameters and elastic energy of the stripe domain, thereby smearing out the random pinning potential, as supported by micromagnetic simulations. The demonstration and comprehensive understanding of antiskyrmion movement along naturally straight tracks offers a new perspective for (anti)skyrmion application in spintronics.

Incommensurate Spin Density Wave in Antiferromagnetic RuO_{2} Evinced by Abnormal Spin Splitting Torque.

Since the discovery of antiferromagnetism, metallic oxide RuO_{2} has exhibited numerous intriguing spintronics properties such as the anomalous Hall effect and anisotropic spin splitting effect. However, the microscopic origin of its antiferromagnetism remains unclear. By investigating the spin splitting torque in RuO_{2}/Py, we found that metallic RuO_{2} exhibits a spatially periodic spin structure which interacts with the spin waves in Py through interfacial exchange coupling. The wavelength of such structure is evaluated within 14-20 nm depending on the temperature, which is evidence of an incommensurate spin density wave state in RuO_{2}. Our work not only provides a dynamics approach to characterize the antiferromagnetic ordering in RuO_{2}, but also offers fundamental insights into the spin current generation due to anisotropic spin splitting effect associated with spin density wave.