BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.

Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.

Transcending membrane barriers: advances in membrane engineering to enhance the production capacity of microbial cell factories.

Microbial cell factories serve as pivotal platforms for the production of high-value natural products, which tend to accumulate on the cell membrane due to their hydrophobic properties. However, the limited space of the cell membrane presents a bottleneck for the accumulation of these products. To enhance the production of intracellular natural products and alleviate the burden on the cell membrane caused by product accumulation, researchers have implemented various membrane engineering strategies. These strategies involve modifying the membrane components and structures of microbial cell factories to achieve efficient accumulation of target products. This review summarizes recent advances in the application of membrane engineering technologies in microbial cell factories, providing case studies involving Escherichia coli and yeast. Through these strategies, researchers have not only improved the tolerance of cells but also optimized intracellular storage space, significantly enhancing the production efficiency of natural products. This article aims to provide scientific evidence and references for further enhancing the efficiency of similar cell factories.

Hedgehog signaling regulates bone homeostasis through orchestrating osteoclast differentiation and osteoclast-osteoblast coupling.

Imbalance of bone homeostasis induces bone degenerative diseases such as osteoporosis. Hedgehog (Hh) signaling plays critical roles in regulating the development of limb and joint. However, its unique role in bone homeostasis remained largely unknown. Here, we found that canonical Hh signaling pathway was gradually augmented during osteoclast differentiation. Genetic inactivation of Hh signaling in osteoclasts, using Ctsk-Cre;Smof/f conditional knockout mice, disrupted both osteoclast formation and subsequent osteoclast-osteoblast coupling. Concordantly, either Hh signaling inhibitors or Smo/Gli2 knockdown stunted in vitro osteoclast formation. Mechanistically, Hh signaling positively regulated osteoclast differentiation via transactivation of Traf6 and stabilization of TRAF6 protein. Then, we identified connective tissue growth factor (CTGF) as an Hh-regulatory bone formation-stimulating factor derived from osteoclasts, whose loss played a causative role in osteopenia seen in CKO mice. In line with this, recombinant CTGF exerted mitigating effects against ovariectomy induced bone loss, supporting a potential extension of local rCTGF treatment to osteoporotic diseases. Collectively, our findings firstly demonstrate that Hh signaling, which dictates osteoclast differentiation and osteoclast-osteoblast coupling by regulating TRAF6 and CTGF, is crucial for maintaining bone homeostasis, shedding mechanistic and therapeutic insights into the realm of osteoporosis.

Comparison of bleb morphologies between phacoemulsification combined with Ex-PRESS mini shunt implantation, phacotrabeculectomy and trabeculectomy alone: a two-year retrospective in vivo confocal microscopy study.

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.

The impact of lymphadenectomy on ovarian clear cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) shares treatment strategies with epithelial ovarian cancer (EOC). Due to OCCC's rarity, there's a lack of prospective studies on its surgery, resulting in heterogeneous and limited existing data. This study aims to clarify the prognostic significance of lymphadenectomy in OCCC patients. METHODS: We systematically searched Web of Science, Scopus, PubMed, and Google Scholar until July 2023 for studies investigating lymphadenectomy's effects on OCCC patients. We calculated pooled hazard ratios (HR) with 95% confidence intervals (CI). This study is registered in PROSPERO (CRD42021270460). RESULTS: Among 444 screened articles, seven studies (2883 women) met inclusion criteria. Our analysis revealed that lymphadenectomy significantly improved disease-specific survival (DSS) (HR = 0.76, 95%CI = 0.60-0.95, P = 0.02) and disease-free survival (DFS) (HR = 0.58, 95%CI = 0.34-0.99, P = 0.05). However, it did not significantly affect overall survival (OS) (HR = 0.80, 95%CI = 0.60-1.06, P = 0.12) or progression-free survival (PFS) (HR = 0.95, 95%CI = 0.64-1.42, P = 0.79). Notably, some earlier studies reported no survival benefit, warranting cautious interpretation. CONCLUSION: Lymphadenectomy does not significantly enhance OS and PFS for OCCC but does improve DFS and DSS. Tailoring treatment to individual patient profiles is imperative for optimal outcomes. Precise preoperative or intraoperative lymph node metastasis detection is essential for identifying candidates benefiting from lymphadenectomy. Collaborative international efforts and an OCCC database are pivotal for refining future treatment strategies.

Double-Branch Multi-Scale Contextual Network: A Model for Multi-Scale Street Tree Segmentation in High-Resolution Remote Sensing Images.

Street trees are of great importance to urban green spaces. Quick and accurate segmentation of street trees from high-resolution remote sensing images is of great significance in urban green space management. However, traditional segmentation methods can easily miss some targets because of the different sizes of street trees. To solve this problem, we propose the Double-Branch Multi-Scale Contextual Network (DB-MSC Net), which has two branches and a Multi-Scale Contextual (MSC) block in the encoder. The MSC block combines parallel dilated convolutional layers and transformer blocks to enhance the network's multi-scale feature extraction ability. A channel attention mechanism (CAM) is added to the decoder to assign weights to features from RGB images and the normalized difference vegetation index (NDVI). We proposed a benchmark dataset to test the improvement of our network. Experimental research showed that the DB-MSC Net demonstrated good performance compared with typical methods like Unet, HRnet, SETR and recent methods. The overall accuracy (OA) was improved by at least 0.16% and the mean intersection over union was improved by at least 1.13%. The model's segmentation accuracy meets the requirements of urban green space management.

Deciphering and investigating fragment mechanism of quinolones using multi-collision energy mass spectrometry and computational chemistry strategy.

RATIONALE: Quinolones show characteristic fragments in mass spectrometry (MS) analysis due to their common core structures, and energy-dependent differences among these fragments are generated through the same fragmentation pathway of different molecules. Computational chemistry, which provides quantitative results of molecule parameters, is helpful for investigating the mechanisms of chemistry. METHODS: MS/MS spectra of five quinolones, namely norfloxacin (NOR), enoxacin (ENO), enrofloxacin (ENR), gatifloxacin (GAT), and lomefloxacin (LOM), were acquired for deciphering fragmentation pathways under multi-collision energy (CE). Computational methods were used for excluding little possibility pathways from the point of view of energy and stable conformations, whereas optimized collision energy (OCE) and maximum relative intensity (MRI) of major competitive fragments were investigated and confirmed using computational results. RESULTS: Fragmentation results of NOR, ENO, ENR, and GAT were deciphered using experimental and computational data, of which fragmentation regularities were summarized. Fragmentation pathways of LOM were deciphered under the guidance of foregoing regularities. Meanwhile, the whole process was validated by comparing OCE and MRI and computational energy results, which showed good agreement. CONCLUSIONS: A strategy for explaining quinolone fragmentation results of multi-CE values and deciphering fragment mechanism using computational methods was developed. Relevant data and strategy may provide ideas for how to design and decipher new drug molecules with similar structures.

A pre-column derivatization high-performance liquid chromatography method for simultaneous determination of short-chain and medium-chain fatty acids in a fecal sample.

Short-chain and medium-chain fatty acids have plentiful biological functions, which play a crucial role in the diagnosis and therapy of many diseases. Herein, a new method for simultaneous quantifying 17 short-chain and medium-chain fatty acids with high-performance liquid chromatography coupled with an ultraviolet detector was developed and the pre-column derivatization by indole-3-acetic acid hydrazide was performed to improve the separation and detection. The conditions of the derivatization reaction were systematically investigated. Subsequently, the method was validated and the results showed a satisfactory linearity (linear regression coefficients > 0.9969), the limit of detection (4.0×10-3 -1.9×10-2 µmol/L), precision (0.9%-7.3% for intra-day and 2.0%-9.8% for inter-day), recovery (90.0%-109.1% with relative standard deviation <7.7%) and stability (0.1%-3.3% for standard solution and 0.2%-3.9% for fecal sample). Finally, the established method was successfully applied to quantify short-chain and medium-chain fatty acids in the feces of healthy control and diabetic rats. Eleven kinds of short-chain and medium-chain fatty acids were detected and six of them showed a significant difference between the control group and the model group.

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.

Simultaneous quantification of fatty acids in serum with dual derivatization by liquid chromatography-tandem mass spectrometry.

Fatty acids have multitudinous biological functions and play a crucial role in many biological processes, but due to poor ionization efficiency and lack of appropriate internal standards, the comprehensive quantification of fatty acids by liquid chromatography-tandem mass spectrometry is still challenging. In this study, a new, accurate, and reliable method for quantifying 30 fatty acids in serum using dual derivatization was proposed. Indole-3-acetic acid hydrazide derivants of fatty acids were used as the internal standard and indole-3-carboxylic acid hydrazide derivants of them were used to quantify. The derivatization conditions were systematically optimized and the method validation results showed good linearity with R2  > 0.9942, low detection limit (0.03-0.6 nM), precision (1.6%-9.8% for intra-day and 4.6%-14.1% for inter-day), recovery (88.2%-107.2% with relative standard deviation < 10.5%), matrix effect (88.3%-105.2% with the relative standard deviation < 9.9%) and stability (3.4%-13.8% for fatty acids derivants in 24 h at 4°C and 4.2%-13.8% for three freeze-thaw cycles). Finally, this method was successfully applied to quantify fatty acids in serum samples of Alzheimer's patients. In contrast to the healthy control group, nine fatty acids showed a significant increase in the Alzheimer's disease group.

Ocular Characteristics of Pseudophakic Eyes with Malignant Glaucoma.

INTRODUCTION: The aim of the study was to investigate the clinical characteristics and treatment outcomes of the pseudophakic eyes with malignant glaucoma (MG). METHODS: This retrospective case-control study enrolled 53 eyes of 47 patients with primary angle-closure glaucoma having cataract surgery history, including 19 patients (25 eyes) diagnosed with MG and 28 patients (28 eyes) without MG as the match. Among patients diagnosed with MG, 14 patients (18 eyes) underwent zonulo-hyaloido-vitrectomy (ZHV) and the other 5 patients (7 eyes) received conservative treatments. The visual acuity, refraction status, intraocular pressure (IOP), extent of peripheral anterior synechia, classes of anti-glaucoma medications, and ultrasound biomicroscopy (UBM) examination were recorded before cataract surgery, at the diagnosis of MG, and 3 months after ZHV or atropine application, respectively. RESULTS: In the pseudophakic eyes with MG, the IOP cannot be well controlled compared to the matched eyes (27.24 ± 8.72 mm Hg vs. 14.30 ± 2.63 mm Hg, p < 0.001). In addition, there was a difference in the average spherical equivalent refractive error between 2 groups of patients (-2.23 ± 0.84 D in MG vs. -0.12 ± 0.64 D in the matched eyes, p < 0.001). By UBM analysis, the anterior chamber depth (ACD) was shallower in MG than that in the matched eyes (2.34 ± 0.20 mm vs. 3.47 ± 0.29 mm, p < 0.001). The difference between the anterior vault distance of the pseudophakic eyes with MG and that of the matched eyes was also significant (p < 0.001). After treated with ZHV, the IOP was greatly decreased from 27.84 ± 10.14 mm Hg to 15.85 ± 4.41 mm Hg (p < 0.001). The refractive error also changed from -2.11 ± 0.91 D to +0.42 ± 0.99 D (p < 0.001). At the same time, the central ACD was significantly deepened from 2.30 ± 0.39 mm to 3.30 ± 0.31 mm (p < 0.001). CONCLUSION: Uncontrolled IOP and shallow anterior chamber both centrally and peripherally are the primary clinical characteristics for the pseudophakic eyes with MG. An unexpected refractive error or myopic shift for the eyes with PACG after cataract surgery can be an important hint for diagnosis of MG. The typical UBM image is an anterior displacement of the lens-iris diaphragm and a bow-shaped change of the intraocular lens. It is an effective way to treat pseudophakic MG with the ZHV through a peripheral iridectomy.

A Google Trends analysis revealed global public interest and awareness of nasal polyps.

INTRODUCTION: Nasal polyps (NPs) is a common upper airway inflammatory disorder with a huge negative burden on both the quality of life and costs to patients. However, NPs patients remain undiagnosed and untreated in a timely, which may be due to a lack of disease-related awareness. Google Trends (GT) is an online and open tool, which can provide real-world data on health informatics worldwide. OBJECTIVES: This study aimed to explore global public interest and awareness in nasal polyps (NPs) by performing a GT analysis. METHODS: Data on relative search volume (RSV) for NPs globally were collected by the public website Google Trends from January 2007 to December 2021. Top-related topics, rising-related topics, and regions were extracted for further analysis. Seasonal variation analysis, the latitude difference analysis, and the rising-related topics between the developed countries and the developing countries were analyzed. A P value less than 0.05 was considered statistically significant. RESULTS: The average searching strength showed an overall increasing trend, although with slight fluctuation. The public interest of NPs focuses on the symptoms and treatment for NPs and changes with time. For seasonal variation countries, the peak for the RSV occurred in winter and the bottom in summer. A region in higher latitudes may yield more RSV than that in lower latitudes. The rising-related topics in the recent 5 years reflected the significant differences in treatment and public interest of NPs between the developed and developing countries. CONCLUSIONS: Google Trends analysis revealed global public interest and awareness of the evolution of trends and related topics in nasal polyps over time. Geographic distribution and seasonal variation may be potential trigger factors for NPs, and the public's interest in treatment especially biologics is rising.

Exposure to di (2-ethylhexyl) phthalate causes locomotor increase and anxiety-like behavior via induction of oxidative stress in brain.

Di (2-ethylhexyl) phthalate (DEHP) is one of the most prevalent xenoestrogen endocrine disruptor in daily life. A growing number of studies showed that DEHP could exhibit long-term adverse health effects on the human body, particularly in the liver, kidneys, heart and reproductive systems. However, the impact of oral intake of DEHP on the nervous system is extremely limited. In the present study, the adult C57BL/6J male mice were intragastrically administered with two dosages of DEHP for 35 days. The behavioral parameters were assessed using the elevated plus maze and open-field test. The mRNA expression levels of neuropeptides and the oxidative stress-associated proteins were detected by qPCR and western blot seperately. The histopathologic alterations of the brain were observed by H&E and Nissl staining. The results demonstrated that DEHP exposure could result in neurobehavioral impairments such as locomotor increase and anxiety-like behavior. Furthermore, pathological damages were clearly observed in the cerebral cortex and hippocampus, accompanied by a decrease in neuropeptides and an increase in oxidative stress, which were all positively correlated with the dose of DEHP. Together, these findings provide valuable clues into the DEHP-induced neurotoxicity.

Metalloporphyrin-Linked Mercurated Graphynes for Ultrastable CO2 Electroreduction to CO with Nearly 100% Selectivity at a Current Density of 1.2 A cm-2.

The electrochemical reduction reaction of carbon dioxide (CO2RR) to the desired feedstocks with a high faradaic efficiency (FE) and high stability at a high current density is of great importance but challenging owing to its poor electrochemical stability and competition with the hydrogen evolution reaction (HER). Guided by theoretical calculations, herein, a series of novel metalloporphyrin-linked mercurated graphynes (Hg-MTPP) were designed as electrocatalysts for CO2RR, since the mercurated graphyne blocks induce a high HER overpotential. Notably, Hg-CoTPP was synthesized and produced a maximum CO FE of 95.6% at -0.76 V (vs reversible hydrogen electrode (RHE)) in an H-type cell, and a CO FE of 91.2% even at -1.26 V (vs RHE), due to a great suppression of HER. The Hg-CoTPP combined with N-doped graphene (Hg-CoTPP/NG) was able to achieve a high CO FE of nearly 100% at a current density of 1.2 A cm-2 and particularly a ground-breaking stability of over 360 h at around 420 mA cm-2 in a flow-type cell. Further experimental and computational results revealed that the mercurated graphyne of Hg-CoTPP brings a high HER overpotential and tunes the d-band electronic states of the metal center that make the d-band center closer to the Fermi level, thus enhancing the bonding of *COOH intermediates on Hg-CoTPP. The introduction of NG could shorten the Co-N coordination bonds, which enhances electron transfer to the metal center to lower the energy barrier for *COOH. Our results illustrated that Hg-MTPP could serve as a new class of two-dimensional (2D) materials and provide a design concept for developing efficient electrocatalysts for CO2RR in commercial applications.

A colorimetric aptasensor based on a hemin/EpCAM aptamer DNAzyme for sensitive exosome detection.

Exosomes are considered as potential biomarkers that can reflect information from their parent cell-associated cancer microenvironment. Recently, aptasensors have been widely used for cancer and tumor exosome detection. Aptamers related to exosome surface proteins are usually used to introduce a sequence; the aptamer is used for exosome recognition, and the introduced sequence is used to form G-quadruplexes and for signal amplification. In this paper, we found that the EpCAM aptamer is rich in guanine and unimolecular G-quadruplex with a two-layer G-tetrad under acidic conditions, and we investigated its topology, thermal stability and dissociation constant with hemin. Based on this, our proposed colorimetric aptamer sensor combines the unmodified EpCAM aptamer with hemin to construct a hemin/G-quadruplex DNAzyme and catalyze the TMB-H2O2 system to generate a strong colorimetric signal. Therefore, colorimetric signal changes were negatively correlated with the exosome concentration. The linear range of the 1 h assay was 106-108 particles per mL, and the detection limit was 3.94 × 105 particles per mL. In addition, this method can detect exosomes in complex fetal bovine serum samples with good specificity and high sensitivity toward exosomes from breast, liver, and lung cancers with abnormal EpCAM protein expression.

The influence of cerebral small vessel diseases on the efficacy of repositioning therapy and prognosis of benign paroxysmal positional vertigo.

Background: Although vascular risk factors have been found to be closely related to the development of benign paroxysmal positional vertigo (BPPV), the relationship between BPPV and cerebral small vessels diseases (CSVDs) has rarely been discussed in literature. This study set out to investigate the efficacy of repositioning therapy and prognosis among BPPV patients with CSVDs. Methods: We enrolled 553 BPPV patients who had undergone brain MRI, and categorized them into two groups based on the presence or absence of CSVDs. After controlling for other confounders using a propensity score matching (PSM) approach, we compared the incidence of recurrence and residual dizziness (RD). Then, we analyzed the recurrence rate and RD incidence in 176 BPPV patients with CSVDs, and assessed potential risk factors. Results: White matter hyperintensity (WMH, 72.2%) and lacunar infarction (LI, 65.9%) were the two CSVDs that were present in the highest proportion among the BPPV patients. The incidence of RD in patients with CSVDs was significantly higher compared to subjects without CSVDs. Patients with RD (n=100, 56.8%) were older, had more severe WMH, and had a higher incidence of brain atrophy; age and higher Fazekas score were independent risk factors. Among the recurrent patients (n=61, 34.7%), the ages were older, the Fazekas score of WMH was higher, and number of LIs was increased; age was the sole independent risk factor. Conclusion: BPPV patients with a combination of CSVD comorbidities, especially elderly patients with WMHs, are more likely to develop RD, which needs to be paid more attention.

Isolation of three glucaric acids from Leonurus japonicus Houtt. by using high-speed countercurrent chromatography combined with semi-preparative high-performance liquid chromatography.

The isomerism of glucaric acids and the complexity of the composition of Leonurus japonicus Houtt. increased the difficulty of the separation of glucaric acids from the herb. In the present study, three glucaric acids were isolated from Leonurus japonicus Houtt. by using high-speed countercurrent chromatography combined with semi-preparative high-performance liquid chromatography. Cation exchange resin chromatography was applied to remove the alkaloids and enrich the glucaric acid fractions. Preliminary separation of the glucaric acid extract by high-speed countercurrent chromatography was carried out at 45℃ by using an optimized solvent system of ethyl acetate/n-butanol/formic acid/water (1:1:0.01:2, v/v/v/v) with satisfied stationary phase retention and separation factor. The semi-preparative high-performance liquid chromatography was used for further separation and purification of the target fractions, and three monomeric compounds were obtained with purities of 90.0, 91.0, and 95.3%. UV spectroscopy, NMR spectroscopy, and mass spectrometry were employed to identify their structures, which were assigned as 2-syringyl glucaric acid, 2,4-disyringyl glucaric acid, and 3,4-disyringyl glucaric acid, respectively, and 2,4-disyringyl glucaric acid was reported for the first time.

Chemical Profiling and Quality Evaluation of Callicarpa Nudiflora from Different Regions in China by UPLC-QTOF-MS Fingerprint.

Callicarpa nudiflora, belonging to the family Verbenaceaae, is wildly used as a traditional Chinese herbal medicine (Luo-hua-zi-zhu) for hemostasis, antibiosis and antiphlogosis in clinic. However, the underlying chemical basis of C. nudiflora for the significant effects remains obscure. Hence, an ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method was established for the characterization of multi-constituents in C. nudiflora. As a result, 57 chemical compounds were identified based on their retention times, accurate masses and MS/MS data, and 20 of them were uncovered for the first time in C. nudiflora. In addition, an optimized UHPLC fingerprint analysis, combined with chemometrics including similarity analysis, principal component analysis and partial least squares-discriminant analysis was developed for quality assessment and origin discrimination of C. nudiflora. Multivariate data analysis revealed the resemblances and differences of C. nudiflora related to regions, while partial least squares-discriminant analysis screened nine characteristic markers including luteoloside, acteoside, luteolin-4'-O-ß-D-glucopyranoside, pachypodol, isoquercitrin, nudifloside, 5,7,3',4'-tetrahydroxy-8-methoxy-6-C-ß-D-glucopyranosylflavone, 7α-acetoxysandaracopimaric acid and sandaracopimaric acid which contributed the most to the classification. This was the first report on the comprehensive profiling of chemical components in C. nudiflora, which helped to uncover the material basis of C. nudiflora and possess potential value for quality evaluation and clinical application purpose.

CoLab: A workshop-based undergraduate research experience for entering college students.

The goal of undergraduate chemistry laboratories is to allow students to learn about chemical systems and key laboratory skills. They should then apply this knowledge to solve problems and connect macroscopic observations in the laboratory with those occurring at the submicroscopic level. Unfortunately, these needs are not met through traditional confirmation labs. Therefore, many chemistry instructors are turning towards research-based labs course-based undergraduate research experiences (CUREs). There are also many cases where summer workshops, often with non-traditional pedagogy, are used for students. This article describes the STEM CoLab Program, a novel type of summer workshop that seeks to build student chemistry knowledge and skills in research and presentation at the beginning of their college work. This program uses the principles of CUREs for students who are just entering the university, mostly as freshmen. Several different phenomena have been investigated during the program. In this paper, we report the overall work of the program from 2016 through 2021 and provide additional details on the program's implementation in 2020 and 2021 when students conducted their work from home, using a combination of a take home research kit for studying salivary amylase "in vitro" and computer-based visualizations of amylase-inhibitor interactions "in silico" using PyMOL and online docking tools.

Mycobacterium tuberculosis effector PPE36 attenuates host cytokine storm damage via inhibiting macrophage M1 polarization.

Tuberculosis caused by Mycobacterium tuberculosis remains a serious global public health threat. Macrophage polarization is crucial for the innate immunity against M. tuberculosis. However, how M. tuberculosis interferes with macrophage polarization is elusive. We demonstrated here that M. tuberculosis PPE36 (Rv2108) blocked macrophage M1 polarization, preventing the cytokine storm, and alleviating inflammatory damage to mouse immune organs. PPE36 inhibited the polarization of THP-1 cell differentiation to M1 macrophages, reduced mitochondrial dehydrogenase activity, inhibited the expression of CD16, and repressed the expression of pro-inflammatory cytokines IL-6 and TNF-α, as well as chemokines CXCL9, CXCL10, CCL3, and CCL5. Intriguingly, in the mouse infection model, PPE36 significantly alleviated the inflammatory damage of immune organs caused by a cytokine storm. Furthermore, we found that PPE36 inhibited the polarization of macrophages into mature M1 macrophages by suppressing the ERK signaling. The study provided novel insights into the function and mechanism of action of M. tuberculosis effector PPE36 both at the cellular and animal level.