Distinctive neurophysiological signatures of analgesia after inflammatory pain in the ACC of freely moving mice.

Preclinical assessments of pain have often relied upon behavioral measurements and anesthetized neurophysiological recordings. Current technologies enabling large scale neural recordings, however, have the potential to unveil quantifiable pain signals in conscious animals for preclinical studies. Although pain processing is distributed across many brain regions, the anterior cingulate cortex (ACC) is of particular interest in isolating these signals given its suggested role in the affective ('unpleasant') component of pain. Here, we explored the utility of the ACC towards preclinical pain research using head-mounted miniaturized microscopes to record calcium transients in freely moving male mice expressing GCaMP6f under the Thy1 promoter. We verified the expression of GCaMP6f in excitatory neurons and found no intrinsic behavioral differences in this model. Using a multimodal stimulation paradigm across naive, pain, and analgesic conditions, we found that while ACC population activity roughly scaled with stimulus intensity, single cell representations were highly flexible. We found only low magnitude increases in population activity after CFA, and insufficient evidence for the existence of a robust nociceptive ensemble in the ACC. However, we found a temporal sharpening of response durations and generalized increases in pairwise neural correlations in the presence of the mechanistically distinct analgesics gabapentin or ibuprofen after (but not before) CFA induced inflammatory pain. This increase was not explainable by changes in locomotion alone. Taken together, these results highlight challenges in isolating distinct pain signals amongst flexible representations in the ACC but suggest a neurophysiological hallmark of analgesia after pain that generalizes to at least two analgesics.Significance Statement Our study measured neural activity in the anterior cingulate cortex (ACC) of transgenic mice to improve measures of pain and analgesia in preclinical models. We found that although ACC population activity scaled with stimulus intensity and could be decoded, single cell representations of sensory stimuli were flexible. Low magnitude increases in ACC population activity were observed after pain, but subpopulations with specific activity changes driven by pain/analgesia were difficult to disambiguate from intrinsic variability. Interestingly, responses were temporally sharpened and exhibited increased cell to cell correlations in the presence of two distinct analgesics after CFA but not before. These distinct neural signatures of analgesia occurring only after pain may broaden our understanding of central mechanisms of pain and analgesia.

Daphnetin protects neurons in an Alzheimer disease mouse model and normal rat neurons by inhibiting BACE1 activity and activating the Nrf2/HO-1 pathway.

The common neurodegenerative disorder Alzheimer disease (AD) is characterized by memory dysfunction and cognitive decline in the elderly. Neuropathological features include aggregated ß-amyloid (Aß) accumulation, neuroinflammation, and oxidative stress in the brain. Daphnetin (DAPH), a natural coumarin derivative, has the potential for inhibiting inflammatory and oxidative responses. We explored neuroprotective roles of DAPH treatment in the APP/PS1 transgenic mouse AD model. DAPH ameliorated spatial learning disabilities in Morris water maze tests and reduced Aß deposition, assessed by immunohistochemistry. It also reduced the Aß content in supernatants of neurons from fetal APP/PS1 mice, assessed by cell-based soluble ELISA. Molecular docking and fluorescence resonance energy transfer-based assay results suggested that DAPH could directly inhibit BACE1 activity. Furthermore, in vitro experiments utilizing isolated rat neurons assessing RNA expression profiling, immunofluorescence, TUNEL assay, and Western-blot analysis, suggested the potential of DAPH for regulating BDNF and GM-CSF expression and mitigating Aß1-42-induced cortical injury, synaptic loss, and apoptosis. HO-1 and Nrf2 mRNA and protein expression were also increased in a dose-dependent manner. These results underscore the potential of DAPH as a neuroprotective agent in reversing memory deficits associated with AD and bolster its candidacy as a multitarget natural small-molecule drug for AD patients.

Enhancing vegetation formation classification: Integrating coarse-scale traditional mapping knowledge and advanced machine learning.

Mapping vegetation formation types in large areas is crucial for ecological and environmental studies. However, this is still challenging to distinguish similar vegetation formation types using existing predictive vegetation mapping methods, based on commonly used environmental variables and remote sensing spectral data, especially when there are not enough training samples. To solve this issue, we proposed a predictive vegetation mapping method by integrating an advanced machine learning algorithm and knowledge in an early coarse-scale vegetation map (VMK). First, we implemented classification using the random forest algorithm by integrating the early vegetation map as an auxiliary feature (VMF). Then, we determined the rationality of classified vegetation types and distinguished the confusing types, respectively, based on the knowledge of the spatial distributions and hierarchies of vegetation. Finally, we replaced each recognized unreasonable vegetation type with its corresponding reasonable vegetation type. We implemented the new method in upstream of the Yellow River based on GaoFen-1 satellite images and other environmental variables (i.e., topographical and climate variables). Results showed that the overall accuracy using the VMK method ranged from 67.7 % to 76.8 %, which was 10.9 % to 13.4 % and 3.2 % to 6.6 %, respectively, higher than that of the method without the early vegetation map (NVM) and the VMF method, based on cross-validation with 20 % to 60 % random training samples. The spatial details of the vegetation map using the VMK method were also more reasonable compared to the NVM and VMF methods. These results indicated that the VMK method can distinctly improve the mapping accuracy at the vegetation formation level by integrating knowledge of existing vegetation maps. The proposed method can largely reduce the requirements on the number of field samples, which is especially important for alpine mountains and arctic region, where collecting training samples is more difficult due to the harsh natural environment.

A Domino Protocol toward High-performance Unsymmetrical Dibenzo[d,d']thieno[2,3-b;4,5-b']dithiophenes Semiconductors.

Unsymmetric organic semiconductors have many advantages such as good solubility, rich intermolecular interactions for potential various optoelectronic applications. However, their synthesis is more challenging due to intricate structures thus normally suffering tedious synthesis. Herein, we report a trisulfur radical anion (S3⋅-) triggered domino thienannulation strategy for the synthesis of dibenzo[d,d']thieno[2,3-b;4,5-b']dithiophenes (DBTDTs) using readily available 1-halo-2-ethynylbenzenes as starting materials. This domino protocol features no metal catalyst and the formation of six C-S and one C-C bonds in a one-pot reaction. Mechanistic study revealed a unique domino radical anion pathway. Single crystal structure analysis of unsymmetric DBTDT shows that its unique unsymmetric structure endows rich and multiple weak S⋅⋅⋅S interactions between molecules, which enables the large intermolecular transfer integrals of 86 meV and efficient charge transport performance with a carrier mobility of 1.52 cm2 V-1 s-1. This study provides a facile and highly efficient synthetic strategy for more high-performance unsymmetric organic semiconductors.

Dietary palm oil enhances Sterol regulatory element-binding protein 2-mediated cholesterol biosynthesis through inducing endoplasmic reticulum stress in muscle of large yellow croaker (Larimichthys crocea).

Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homoeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterisation of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-dehydrocholesterol reductase, which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in the regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.

Multi-aptamer-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of S. pneumoniae and S. aureus.

A novel nucleic acid aptamer nanoprobes-mediated hairpin allosteric and aptamer-assisted CRISPR system for detection of Streptococcus pneumoniae and Staphylococcus aureus is presented. In this fluorescence assay system, utilizing the hairpin allosteric effect caused by the aptamer binding to the target bacteria, the detection of S. pneumoniae is first achieved through changes in fluorescence due to FRET. Subsequently, a Cas12a protein mixture is added to detect S. aureus. The amplified output signal is triggered by two methods to ensure the sensitivity of the method: the synergistic FRET effect is achieved by the assembly of multi-aptamer through the conjugation of streptavidin-biotin, and the trans-cleavage function of CRISPR/Cas 12a. Under the optimized conditions, the proposed hairpin allosteric aptasensor could achieve high sensitivity (a detection limit of 135 cfu/mL) and broad-concentration quantification (dynamic range of 103-107 cfu/mL) of S. pneumoniae. The aptamer-assisted CRISPR system for S. aureus detection showed good linearity (R2 = 0.996) in the concentration range 102-108 cfu/mL, with a detection limit of 39 cfu/mL. No cross-reactivity with other foodborne pathogenic bacteria was observed in both systems. Taking only 55 min, this method of multiple pathogen detection proved to be promising.

Photoswitchable and long-lived seven-membered cyclic singlet diradicals for the bioorthogonal photoclick reaction.

Annularly 1,3-localized singlet diradicals are energetic and homolytic intermediates, but commonly too short-lived for widespread utilization. Herein, we describe a direct observation of a long-lived and seven-membered singlet diradical, oxepine-3,6-dione-2,7-diyl (OXPID), via spectroscopic experiments and also theoretical evidence from computational studies, which is generated via photo-induced ring-expansion of 2,3-diaryl-1,4-naphthoquinone epoxide (DNQO). The photo-generated OXPID reverts to the thermally stable σ-bonded DNQO with t1/2 in the µs level, thus constituting a novel class of T-type molecular photoswitches with high light-energy conversion efficiency (η = 7.8-33%). Meanwhile, the OXPID is equilibrated to a seven-membered cyclic 1,3-dipole as an electronic tautomer that can be captured by ring-strained dipolarophiles with an ultrafast cycloaddition rate (k2CA up to 109 M-1 s-1). The T-type photoswitchable DNQO is then exploited to be a highly selective and recyclable photoclick reagent, enabling spatiotemporal-resolved bioorthogonal ligation on living cell membranes via a tailored DNQO-Cy3 probe.

Compositing Benzothieno[3,2-b]Benzofuran Derivatives with Single-Walled Carbon Nanotubes for Enhanced Thermoelectric Performance.

Although numerous thermoelectric (TE) composites of organic materials and single-walled carbon nanotubes (SWCNTs) have been developed in the past decade, most of the research has been related to polymers without much on organic small molecules (OSMs). In this work, benzothieno[3,2-b]benzofuran (BTBF) and its derivatives (BTBF-Br and BTBF-2Br) were synthesized and their TE composites with SWCNTs were prepared. It is found that the highest molecular orbital level and band gap (Eg) of BTBF, BTBF-Br, and BTBF-2Br gradually decrease upon the introduction of electron-withdrawing Br group on BTBF. These changes significantly improve the Seebeck coefficient and power factor (PF) of OSM/SWCNT composites. An appropriate energy barrier between BTBF-2Br and SWCNTs promotes the energy filtering effect, which further contributes to the enhancement of composites' thermoelectric properties. The composites of SWCNTs and BTBF-2Br with the smallest Eg (4.192 eV) afford the best thermoelectric performance with the room temperature power factor of 169.70 ± 3.46 µW m-1 K-2 in addition to good mechanical flexibility and thermal stability. This study provides a feasible strategy for the preparation of OSM/SWCNT composites with improved thermoelectric properties.

Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation.

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet ß-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).

Evaluation of Serum Fructosamine as Diagnostic Marker of Postoperative Recurrence in the Patients with Breast Cancer.

Objectives: A series of laboratory parameters were screened to identify the proper serum markers that could be used to predict breast cancer recurrence at an early stage. Methods: A case-control retrospective study on 224 patients without postoperative recurrence and 43 patients with postoperative recurrence of breast cancer was performed. The edgeR software package was used to identify the test indicators expressed differently between the two groups. Univariate analysis was used to screen for diagnostic marker that could predict postoperative recurrence of breast cancer. In addition, the differential test indicators at different time points from surgery to recurrence were collected in patients with postoperative recurrence of breast cancer as a verification database. Results: We screened out three test indicators (TBA, GSP, and URBC) for differential expression, which were all expressed downregulated in the postoperative recurrence group of breast cancer. Univariate analysis suggested that only the difference in GSP levels between the two groups was statistically significant (P = 0.001). ROC curve analysis showed that the area under the curve of GSP was 0.662, while the area under the curve of GSP+AFP+CEA+CA125+CA153+age was increased to 0.828. In addition, serum GSP levels were significantly reduced after recurrence compared with before recurrence in breast cancer patients (P < 0.01). Conclusions: In summary, GSP could be used for early diagnosis of breast cancer recurrence after surgery, and the predicted value of combining GSP, tumor markers, and age was better than that of individual indicators.

FRAM-based causal analysis and barrier measures to mitigate dust explosions: A case study.

Both the number of dust explosion accidents and the resulting number of casualties have increased dramatically in recent years. To reduce this risk of dust explosions, we use the functional resonance analysis method (FRAM) to analyze the cause of the dust explosion accident at the Kunshan factory and propose barrier measures to prevent such accidents. The functional units that changed in the production system during the accident and how these functional units coupled to eventually cause the dust explosion were examined and explained. In addition, barrier measures were developed for functional units that changed during production and emergency systems defined to block the propagation of changes between functions and prevent resonance. Through case study, the identification of key functional parameters in both triggering the initial explosion and in then allowing its spread are key to define barriers to prevent a recurrence of such an event. FRAM uses system function coupling instead of traditional linear causality to explain the accident process, and develops barrier measures for changing function units, providing a novel thinking strategy and method for the analysis of accidents and their prevention.

Identification and panoramic analysis of drug response-related genes in triple negative breast cancer using as an example NVP-BEZ235.

Taking NVP-BEZ235 (BEZ235) as an example to screen drug response-related genes (DRRGs) and explore their potential value in triple-negative breast cancer (TNBC). Through high-throughput technique, multidimensional transcriptome expression data (mRNA, miRNA and lncRNA) of BEZ235-treated and -untreated MDA-MB-468 cell lines were obtained. Combined with transcriptome data of the MDA-MB-468 cells and TCGA-TNBC tissues, differential gene expression analysis and WGCNA were performed to identify DRRGs associated with tumor trait by simulating the drug response microenvironment (DRM) of BEZ235-treated patients. Based on DRRGs, we constructed a ceRNA network and verified the expression levels of three key molecules by RT-qPCR, which not only demonstrated the successful construction of a BEZ235-treated cell line model but also explained the antitumor mechanism of BEZ235. Four molecular subtypes related to the DRM with survival difference were proposed using cluster analysis, namely glycolysis subtype, proliferation depression subtype, immune-suppressed subtype, and immune-activated subtype. A novel prognostic signature consisting of four DRRGs was established by Lasso-Cox analysis, which exhibited outstanding performance in predicting overall survival compared with several excellent reported signatures. The high- and low-risk groups were characterized by enrichment of metabolism-related pathways and immune-related pathways, respectively. Of note, the low-risk group had a better response to immune checkpoint blockade. Besides, pRRophetic analysis found that patients in the low-risk group were more sensitive to methotrexate and cisplation, whereas more resistant to BEZ235, docetaxel and paclitaxel. In conclusion, the DRRGs exemplified by BEZ235 are potential biomarkers for TNBC molecular typing, prognosis prediction and targeted therapy. The novel DRRGs-guided strategy for predicting the subtype, survival and therapy efficacy, might be also applied to more cancers and drugs other than TNBC and BEZ235.

Photo-induced defluorination acyl fluoride exchange as a fluorogenic photo-click reaction for photo-affinity labeling.

Photo-click chemistry has emerged as a powerful tool for revolutionizing bioconjugation technologies in pharmacological and various biomimetic applications. However, enriching the photo-click reactions to expand the bioconjugation toolkit remains challenging, especially when focusing on spatiotemporal control endowed by light activation. Herein, we describe a photo-induced defluorination acyl fluoride exchange (photo-DAFEx) as a novel type of photo-click reaction that is mediated through acyl fluorides produced by the photo-defluorination of m-trifluoromethylaniline to covalently conjugate with primary/secondary amines and thiols in an aqueous environment. (TD)-DFT calculations, together with experimental discovery, indicate that the m-NH2PhF2C(sp3)-F bond in the excited triplet state is cleaved by water molecules, which is key to inducing defluorination. Intriguingly, the benzoyl amide linkages built by this photo-click reaction exhibited a satisfactory fluorogenic performance, which allowed visualization of its formation in situ. Accordingly, this photo-controlled covalent strategy was exploited not only for the decoration of small molecules, peptide cyclization and functionalization of proteins in vitro, but also for designing photo-affinity probes targeting endogenous carbonic anhydrase II (hCA-II) in living cells.

Modality-specific sensory and decisional carryover effects in duration perception.

BACKGROUND: The brain uses recent history when forming perceptual decisions. This results in carryover effects in perception. Although separate sensory and decisional carryover effects have been shown in many perceptual tasks, their existence and nature in temporal processing are unclear. Here, we investigated whether and how previous stimuli and previous choices affect subsequent duration perception, in vision and audition. RESULTS: In a series of three experiments, participants were asked to classify visual or auditory stimuli into "shorter" or "longer" duration categories. In experiment 1, visual and auditory stimuli were presented in separate blocks. Results showed that current duration estimates were repelled away from the previous trial's stimulus duration, but attracted towards the previous choice, in both vision and audition. In experiment 2, visual and auditory stimuli were pseudorandomly presented in one block. We found that sensory and decisional carryover effects occurred only when previous and current stimuli were from the same modality. Experiment 3 further investigated the stimulus dependence of carryover effects within each modality. In this experiment, visual stimuli with different shape topologies (or auditory stimuli with different audio frequencies) were pseudorandomly presented in one visual (or auditory) block. Results demonstrated sensory carryover (within each modality) despite task-irrelevant differences in visual shape topology or audio frequency. By contrast, decisional carryover was reduced (but still present) across different visual topologies and completely absent across different audio frequencies. CONCLUSIONS: These results suggest that serial dependence in duration perception is modality-specific. Moreover, repulsive sensory carryover effects generalize within each modality, whereas attractive decisional carryover effects are contingent on contextual details.

Analysis of carotid vulnerable plaque MRI high-risk features and clinical risk factors associated with concomitant acute cerebral infarction.

BACKGROUND: This study aimed to investigate the correlation between the high-risk characteristics of high-resolution MRI carotid vulnerable plaques and the clinical risk factors and concomitant acute cerebral infarction (ACI). METHODS: Forty-five patients diagnosed with a single vulnerable carotid plaque by MRI were divided into two groups based on whether they had ipsilateral ACI. The clinical risk factors and the observation values or frequency of occurrence of high-risk MRI phenotypes of plaque volume, LRNC, IPH and ulcer were statistically compared between the two groups. RESULTS: A total of 45 vulnerable carotid artery plaques were found in 45 patients, 23 patients with ACI and 22 patients without ACI. There were no significant differences in age, sex, smoking, serum TC, TG and LDL between the two groups (all P > 0.05), but the ACI group had significantly more patients with hypertension (P < 0.05) and the without ACI group coronary heart disease (P < 0.05). The volume of vulnerable carotid plaque in the group with ACI (1004.19 ± 663.57 mm3) was significantly larger than that in the group without ACI (487.21 ± 238.64 mm3) (P < 0.05). The phenotype of vulnerable carotid artery plaque was 13 cases of LRNC, 8 cases of LRNC + IPH, 5 cases of LRNC + Ulcer, and 19 cases of LRNC + IPH + Ulcer. There was no significant difference in this distribution between the two groups (all P > 0.05) with the exception of LRNC + IPH + Ulcer. The 14 cases of LRNC + IPH + LRNC + IPH + Ulcer (60.87%) in the group with ACI and was significantly greater than the 5 (22.73%) in patients without ACI (P < 0.05). CONCLUSION: It is preliminarily thought that hypertension is the main clinical risk factor for vulnerable carotid plaques with ACI and the combination of plaque volume with vulnerable carotid plaque and LRNC + IPH + Ulcer is a high-risk factor for complicated ACI. It has high clinical therapeutic value due to the accurate diagnosis of responsible vessels and plaques with high-resolution MRI.

Improved soil surface nitrogen balance method for assessing nutrient use efficiency and potential environmental impacts within an alpine meadow dominated region.

The soil surface nitrogen balance (SSNB) method is commonly used to assess the nutrient use efficiency (NUE) of agricultural systems and any associated potential environmental impacts. However, the nitrogen flow of wide natural grasslands and other natural areas differ from that of artificial croplands and mown grasslands. In this study, we integrated root growth and the important nutrient resorption process into the SSNB model and used the improved model to clarify the nitrogen (N) flow and balance in the Three Rivers Headwater Region (TRHR)-an area dominated by alpine meadows-from 2012-2019. In the grassland system, the N surplus (ΔN) was 0.274 g m-2 year-1, and root return (BLD) dominated the N input, accounting for 67% of the total input (3.924 g m-2 year-1). N resorption was the main internal N flow in the grassland system (1.079 g m-2 year-1), and 30% of grassland uptake (NUP-grass). The ΔN of the agricultural system was 1.097 g m-2 year-1, which was four times that of the grassland, and chemical fertilizer was the largest input, accounting for 84% of the total input. The NUE in grassland was 93%, which suggests a risk of soil mining and degradation, while that of cropland was 76% and within an ideal range. The ΔN provides a robust measure of river N export, the TRHR was divided into three catchments, and the export coefficient was 16.14%-55.68%. The results of this study show that the improved SSNB model can be applied to a wide range of natural grasslands that have high root biomass and resorption characteristics.

Neural correlates of aftereffects induced by adaptations to single and average durations.

Duration perception can be heavily distorted owing to repetitive exposure to a relatively long or short sensory event, often causing a duration aftereffect. Here, we used a novel procedure to show that adaptations to both single and average durations produced the duration aftereffect. Participants completed a duration reproduction task (Experiment 1) or a duration category rating task (Experiment 2) after long-term adaptations to a stimulus of medium duration and to stimuli of averagely medium duration. We found that adaptations to both single and average durations resulted in duration aftereffects. The simultaneously recorded functional magnetic resonance imaging (fMRI) data revealed that the reduction in neural activity due to long-term adaptation to single duration was observed in the right supramarginal gyrus (SMG) of the parietal lobe, while adaptation to average duration resulted in fMRI adaptations in the left postcentral gyrus (PCG) and middle cingulate gyrus (MCG). At the individual level, the magnitude of the behavioral aftereffect was positively correlated with the magnitude of fMRI adaptation in the right SMG after adaptation to single duration, while there were no significantly positive correlations between the behavioral aftereffect and fMRI adaptations in the left PCG and MCG. These results suggest that there are different neural mechanisms for aftereffects caused by adaptations to single and average durations.

The prevalence of osteoporosis in China, a community based cohort study of osteoporosis.

Background: Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods: The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results: After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80-34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58-21.87%) and 38.05% (95% CI, 37.22-38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions: This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Photo-regulated genetic encoding of dibenzo[c,g][1,2]diazocine on proteins via configuration switching.

We report two evolved Methanosarcina mazei pyrrolysine tRNA synthetases to genetically incorporate the isomers of dibenzo[c,g][1,2]diazocine-alanine (DBDAA) into proteins either in the dark or under regulation of 405 nm photo-stimulation. The genetic-encoded DBDAA realizes photo-tuning of enzymatic activity via the host-guest recognition of cucurbit[7]uril.

A facile and light-controllable drug combination for enhanced photopharmacology.

We investigated the feasibility of creating cyclic azobenzene/azobenzene-based photo-switchable drugs that can fine-tune antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with light dependence. Furthermore, a "light-controlled drug combination" of these obtained drugs could be reversibly controlled to efficiently improve the antibiotic effect so as to reduce the minimum inhibitory concentrations (MICs) with different wavelength light illumination. Importantly, their antimicrobial activity could be easily manipulated by using light in bacterial patterning studies with high spatiotemporal precision, which might allow for localized activation of drugs and provide an alternative solution for practical clinical application in photopharmacology.