Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor-expressing T (CAR-T) cells induce robust antitumor responses in patients with hematologic malignancies. However, CAR-T cells exhibit only limited efficacy against solid tumors such as hepatocellular carcinoma (HCC), partially due to their limited expansion and persistence. CD8+ T cells, as key components of the adaptive immune response, play a central role in antitumor immunity. Aerobic glycolysis is the main metabolic feature of activated CD8+ T cells. In the tumor microenvironment, however, the uptake of large amounts of glucose by tumor cells and other immunosuppressive cells can impair the activation of T cells. Only when tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment have a glycolytic advantage might the effector function of T cells be activated. Glucose transporter type 1 (GLUT1) and acylglycerol kinase (AGK) can boost glycolytic metabolism and activate the effector function of CD8+ T cells, respectively. In this study, we generated GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK for the treatment of HCC. GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK specifically and effectively lysed GPC3-positive tumor cells in vitro in an antigen-dependent manner. Furthermore, GLUT1 or AGK overexpression protected CAR-T cells from apoptosis during repeated exposures to tumor cells. Compared with second-generation CAR-T cells, GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK exhibited greater CD8+ T-cell persistence in vivo and better antitumor effects in HCC allograft mouse models. Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

Exploring the Formation of Chemical Markers in Chaste Honey by Comparative Metabolomics: From Nectar to Mature Honey.

Identification of chemical markers is important to ensure the authenticity of monofloral honey; however, the formation of chemical markers in honey has received little attention. Herein, using comparative metabolomics, we first identified chemical markers in chaste honey and then explored their formation and accumulation from nectar to mature honey. We identified agnuside and p-hydroxybenzoic acid glucosides as chemical markers for chaste honey. Besides, we developed an UHPLC-MS/MS method for quantifying these markers and found that their levels varied significantly across sample sources. We compared the presence of these compounds in chaste nectar and mature honey. The outcomes underscore that these characteristic compounds are not simply delivered from nectar to mature honey, and activities of honeybees (collecting and processing) play a pivotal role in their formation and accumulation. These observations shed light on how mature honey can form its unique qualities with a rich assortment of natural bioactive compounds, potentially supporting health benefits.

Application Value of CYFRA21-1 Combined with NSE, CEA, and SCC-Ag in Lung Cancer.

BACKGROUND: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). METHODS: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. RESULTS: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. CONCLUSIONS: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC.

Chemical markers of a rare honey from the traditional spice plant Amomum tsao-ko Crevost et Lemarié, via integrated GC-MS and LC-MS approaches.

The precious medicinal plant, Amomum tsao-ko Crevost et Lemarié, is the nectariferous plant from which the rare Amomum tsao-ko Crevost et Lemarié honey (ATH) is produced. Presently, chemical markers for authentication of this honey are not available due to the lack of data on its chemical composition. Here, we analyzed the volatile components and their odor activity values (OAVs), which revealed that the unique aroma was mildly flowery and fruity, accompanied by subtle sweet and fresh undertones. Since non-volatile chemicals are more reliable markers for routine authentication, we used a metabolomic approach combined with NMR-based identification to find and confirm a suitable compound to unambiguously distinguish ATH from other honeys. Isorhamnetin 3-O-neohesperidoside ranged from 3.62 to 9.38 mg/kg in ATH and was absent in the other tested honeys. In sum, the study uncovered unique chemical characteristics of ATH that will be helpful to control its quality.

Chaste honey in long term-storage: Occurrence and accumulation of Maillard reaction products, and safety assessment.

Honey, a natural sweetener that can be stored long-term, is prone to Maillard reactions. Maillard reaction products (MRPs), such as 5-hydroxymethylfurfural (5-HMF), α-dicarbonyl compounds (α-DCs), and advanced glycation end products (AGEs), negatively affect human health. We analyzed MRP accumulation in chaste honey over four years. In the first year, α-DCs were dominant with total contents of 509.7 mg/kg. In the second year, Amadori compounds increased, accounting for the largest percentage. Their formation at the initial stage showed inhibition of the Maillard reaction over time. AGE contents were approximately 1.00 mg/kg over four years, which is negligible compared to other foods. Increased 5-HMF was significantly correlated with storage time (p < 0.01), making it a suitable indicator of honey quality. Due to the lack of MRP risk assessments, we compared our findings with daily intake of MRPs from other foods, and the levels of MRPs in honey over four years are acceptable.

Comprehensive study of volatile compounds of rare Leucosceptrum canum Smith honey: Aroma profiling and characteristic compound screening via GC-MS and GC-MS/MS.

Monofloral honeys are highly valued for their unique flavors and potential health benefits. In this study, the aromatic attributes of rare Leucosceptrum canum Smith honey (LCH) were characterized by GC-MS coupled with GC-MS/MS. Based on their odor contribution rates (OCRs), linalool (74.22%), 3-methyl-1-butanol (18.19%), benzeneacetaldehyde (1.31%) and lilac aldehyde B (2.78%) were largely responsible for the unique and complex flavor of LCH - flowery, spicy, sweet, fruity and fresh. Compared to other tested honeys, linalool (0.18 mg/kg), which has known antibacterial properties, was higher in LCH. However, it was not the main antibacterial compound in LCH, suggesting as of now unknown antibacterial compounds. This study provides the first aromatic profile of LCH, which will be useful for the authentication of LCH and for uncovering the mechanisms behind its perceived health benefits.

Microstructure Formation and Mechanical Properties of Metastable Titanium-Based Gradient Coating Fabricated via Intense Pulse Ion Beam Melt Mixing.

The unique flash heating characteristics of intense pulsed ion beams (IPIB) offer potential advantages to fabricate high-performance coatings with non-equilibrium structures. In this study, titanium-chromium (Ti-Cr) alloy coatings are prepared through magnetron sputtering and successive IPIB irradiation, and the feasibility of IPIB melt mixing (IPIBMM) for a film-substrate system is verified via finite elements analysis. The experimental results reveal that the melting depth is 1.15 µm under IPIB irradiation, which is in close agreement with the calculation value (1.18 µm). The film and substrate form a Ti-Cr alloy coating by IPIBMM. The coating has a continuous gradient composition distribution, metallurgically bonding on the Ti substrate via IPIBMM. Increasing the IPIB pulse number leads to more complete element mixing and the elimination of surface cracks and craters. Additionally, the IPIB irradiation induces the formation of supersaturated solid solutions, lattice transition, and preferred orientation change, contributing to an increase in hardness and a decrease in elastic modulus with continuous irradiation. Notably, the coating treated with 20 pulses demonstrates a remarkable hardness (4.8 GPa), more than twice that of pure Ti, and a lower elastic modulus (100.3 GPa), 20% less than that of pure Ti. The analysis of the load-displacement curves and H-E ratios indicates that the Ti-Cr alloy coated samples exhibit better plasticity and wear resistance compared to pure Ti. Specifically, the coating formed after 20 pulses exhibits exceptional wear resistance, as demonstrated by its H3/E2 value being 14 times higher than that of pure Ti. This development provides an efficient and eco-friendly method for designing robust-adhesion coatings with specific structures, which can be extended to various bi- or multi-element material systems.

Electrochemical determination of benomyl using MWCNTs interspersed graphdiyne as enhanced electrocatalyst.

Graphdiyne (GDY) has attracted a lot of interest in electrochemical sensing application with the advantages of a large conjugation system, porous structure, and high structure defects. Herein, to further improve the sensing effect of GDY, conductive MWCNTs were chosen as the signal accelerator. To get a stable composite material, polydopamine (PDA) was employed as connecting bridge between GDY and MWCNTs-NH2, where DA was firstly polymerized onto GDY, followed by covalently linking MWCNTs-NH2 with PDA through Michael-type reaction. The formed GDY@PDA/MWCNTs-NH2 composite was then explored as an electrochemical sensor for benomyl (Ben) determination. GDY assists the adsorption and accumulation of Ben molecules to the sensing surface, while MWCNTs-NH2 can enhance the electrical conductivity and electrocatalytic activity, all of which contributing to the significantly improved performance. The proposed sensor displays an obvious oxidation peak at 0.72 V (vs. Hg|Hg2Cl2) and reveals a wide linear range from 0.007 to 10.0 µM and a low limit of detection (LOD) of 1.8 nM (S/N = 3) toward Ben detection. In addition, the sensor shows high stability, repeatability, reproducibility, and selectivity. The feasibility of this sensor was demonstrated by detecting Ben in apple and cucumber samples with a recovery of 94-106% and relative standard deviations (RSDs) less than 2.3% (n = 5). A sensitive electrochemical sensing platform was reported for benomyl (Ben) determination based on a highly stable GDY@PDA/MWCNTs-NH2 composite.

α-Dicarbonyl compounds in food products: Comprehensively understanding their occurrence, analysis, and control.

α-Dicarbonyl compounds (α-DCs) are readily produced during the heating and storage of foods, mainly through the Maillard reaction, caramelization, lipid-peroxidation, and enzymatic reaction. They contribute to both the organoleptic properties (i.e., aroma, taste, and color) and deterioration of foods and are potential indicators of food quality. α-DCs are also important precursors to hazardous substances, such as acrylamide, furan, advanced lipoxidation end products, and advanced glycation end products, which are genotoxic, neurotoxic, and linked to several diseases. Recent studies have indicated that dietary α-DCs can elevate plasma α-DC levels and lead to "dicarbonyl stress." To accurately assess their health risks, quantifying α-DCs in food products is crucial. Considering their low volatility, inability to absorb ultraviolet light, and high reactivity, the analysis of α-DCs in complex food systems is a challenge. In this review, we comprehensively cover the development of scientific approaches, from extraction, enrichment, and derivatization, to sophisticated detection techniques, which are necessary for quantifying α-DCs in different foods. Exposure to α-DCs is inevitable because they exist in most foods. Recently, novel strategies for reducing α-DC levels in foods have become a hot research topic. These strategies include the use of new processing technologies, formula modification, and supplementation with α-DC scavengers (e.g., phenolic compounds). For each strategy, it is important to consider the potential mechanisms underlying the formation and removal of process contaminants. Future studies are needed to develop techniques to control α-DC formation during food processing, and standardized approaches are needed to quantify and compare α-DCs in different foods.

Screening and verification of genes related to polycystic ovary syndrome.

OBJECTIVE: To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). METHODS: By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. RESULTS: From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. CONCLUSIONS: ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.

Identification of the maturity of acacia honey by an endogenous oligosaccharide: A preliminary study.

Mature honeys that brew naturally in the hive develop distinct bioactive components, and thus carry a higher premium due to their superior quality. However, how to identify mature honeys remains difficult. Trace oligosaccharides are a likely source of biomarkers to indicate maturity. Here, we profiled trace oligosaccharides in acacia honey by GC-MS and used a metabolomics strategy to screen oligosaccharides that distinguish honeys with different maturities. Turanose content increased gradually in acacia honey samples and was closely related to the days stored in the hive (p < 0.05). To accurately quantify turanose, a UPLC-ELSD method was developed. Using the established method, honeys with ≥1.20 g/100 g of turanose could be classified as mature acacia honey. Based on the preliminary study, 500 commercial acacia honeys were analyzed, and only 77.2 % of these samples had a satisfactory level of turanose. This work offers a potential method to evaluate the quality of honeys.

A three-dimensional inversion-recovery with real reconstruction sequence with an ultralong repetition time for endolymphatic hydrops of Meniere disease after intravenous enhancement: a preliminary application / 中华放射学杂志

Objective:To evaluate the value of a three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with an ultralong repetition time (TR) for the endolymphatic hydrops (EH) of Meniere disease (MD) after intravenous gadolinium administration, and compare it with a heavily T 2-weighted three-dimensional fluid-attenuated inversion recovery (hT 2-3D-FLAIR) sequence. Methods:From July 2021 to July 2022, 52 definite MD patients (58 ears) were retrospectively enrolled at Zhongshan Hospital, Fudan University. The 3D-real IR with an ultralong TR (16 000 ms) and hT 2-3D-FLAIR sequences were performed four hours after intravenous single-dose gadolinium administration. The image quality of the two sequences was rated. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in the two sequence. The EH of cochlear and vestibular was graded, and EH detection rates were calculated. Scores of the two sequences were compared using the paired Wilcoxon signed rank test. Paired t test was used to compare the differences of the SNR and CNR. McNemar test was performed to compare the EH detection rate between the two sequences. Results:The score of the 3D-real IR [3 (3, 4)] was significantly higher than that of the hT 2-3D-FLAIR [2.5 (2, 3), Z=-6.06, P<0.001]. No significant difference was found in SNR of 3D-real IR and hT 2-3D-FLAIR (11.4±6.5 and 12.3±3.7, t=-1.38, P=0.175). CNR of the 3D-real IR (21.7±9.3) was significantly higher than that of the hT 2-3D-FLAIR (9.7±3.8, t=10.67, P<0.001). Using 3D-real IR sequence, the EH detection rate of cochlear (89.7%, 52/58) was higher than using hT 2-3D-FLAIR (67.2%, 39/58, χ 2=11.10, P<0.001). No significant difference was found in the EH detection rate of vestibular between 3D-real IR (77.6%, 45/58) and hT 2-3D-FLAIR (74.1%, 43/58, χ 2=0.50, P=0.500). Conclusion:Compared with hT 2-3D-FLAIR sequence, the 3D-real IR with an ultralong TR can improve the depiction of EH in MD patients after intravenous single-dose gadolinium administration. It can provide higher image quality and detection rate of EH.

Value of conventional MRI and high resolution diffusion weighted imaging in differentiation nasopharynx and skull base osteomyelitis from locoregionally advanced nasopharyngeal carcinoma / 中华放射学杂志

Objective:To investigate the value of conventional MRI and high resolution diffusion weighted imaging (DWI) for preoperative discrimination between nasopharyngeal-skull base osteomyelitis (NP-SBO) and locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Methods:From January 2017 to October 2021, 27 patients of NP-SBO and 32 patients of LA-NPC were retrospectively analyzed at the Eye & ENT Hospital of Fudan University. The clinical characteristics and conventional MRI features were collected, and the apparent diffusion coefficient (ADC) values of polygonal (ADC polygonal) and small circle were measured from readout segmentation of long variable echo-trains (RESOLVE) DWI. MRI features included laterality, margin, signal intensity of T 1WI and T 2WI, enhancement degree, component, abscess, deep mucosal white line, bone invasion, lymph nodes involvement and other accompany symphtoms. The independent sample t test, χ 2 test or Fisher exact test were used to compare the features and ADC values of the NP-SBO and LA-NPC groups. The logistic regression was applied to select independent predictors in the distinguishing LA-NPC from NP-SBO. Then, the conventional MRI model, ADC model and conventional MRI in combination with ADC model were built. The area under the receiver operating characteristic curve (AUC) of models were compared using DeLong test. Results:The age, diabetic status, cranial nerve deficits, inner component, abscess, deep mucosal white line, lymph nodes involvement and ADC polygonal were significantly different between NP-SBO and LA-NPC groups ( P<0.05). The logistic regression analysis showed that ADC polygonal (OR=0.972, 95%CI 0.951-0.993, P=0.011) and abscess (OR=0.101, 95%CI 0.013-0.774, P=0.027) were the independent predictors in the discrimination of NP-SBO and LA-NPC. The AUC (95%CI) of conventional MRI model (abscess), ADC model (ADC polygonal) and combination model were 0.634 (0.499-0.756), 0.870 (0.757-0.943), and 0.925(0.829-0.979), respectively. The AUC of combination model was higher than that of conventional MRI model ( Z=4.77, P<0.001), while there was no difference between combination model and ADC model ( Z=1.87, P=0.062). The AUC of conventional MRI model was lower than that of ADC model ( Z=2.84, P=0.005). Conclusion:Conventional MRI in combination with RESOLVE DWI shows good performance in differentiating between NP-SBO and LA-NPC, especially for abscess in combination with ADC polygonal value.

[Detection of Fusion Gene and Prognosis Analysis in Children with Acute Lymphoblastic Leukemia of Different Immunophenotypes].

OBJECTIVE: To observe the detection of fusion gene in children with acute lymphoblastic leukemia (ALL) of different immunophenotypes, and analyze the relationship between fusion gene and prognosis. METHODS: The clinical data of 86 children with ALL treated in the hospital from May 2015 to May 2020 were retrospectively analyzed, the immunophenotypes and the prognosis of children were recorded, the detection of fusion gene in ALL children with different immunophenotypes was compared, the relationship between detection of fusion gene and prognosis was analyzed. RESULTS: The results of bone marrow immunophenotype showed that there were 13 cases of T cell type and 73 cases of B cell type in 86 children with ALL. The detection rate of fusion gene SIL-TAL1 in ALL children with T cell type was significantly higher than that in ALL children with B cell type (P<0.05). The detection rates of fusion genes BCR-ABL1, E2A-PBX1 and TEL-AML1 in ALL children with B cell type were higher than those in ALL children with T cell type, but the differences were not statistically significant (P>0.05). Followed up for 8-12 months, recurrence was taken as the end point, the average follow-up time was (10.14±1.75) months, in 86 children with ALL 15 cases recurred (17.44%). The recurrence curve drawn by Kaplan-Meier method showed that the median recurrence time of 15 children with recurrent ALL was 9 months. The proportions of positive minimal residual disease and extramedullary infiltration in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (P<0.05). The detection rates of fusion genes BCR-ABL and SIL-TAL1 in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that positive minimal residual lesions, extramedullary infiltration, and detection of fusion genes BCR-ABL and SIL-TAL1 were risk factors for poor prognosis in children with ALL (OR>1, P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of combined detection of fusion gene BCR-ABL and SIL-TAL1 for predicting the poor prognosis of ALL children was >0.707, which had a certain predictive value. CONCLUSION: There are differences in fusion genes among ALL children with different immunophenotypes, minimal residual disease, extramedullary infiltration, and fusion gene are associated with prognosis of ALL children. Fusion gene detection can be used as new method to predict the prognosis of children with ALL.

Identification of Four Biomarkers of Human Skin Aging by Comprehensive Single Cell Transcriptome, Transcriptome, and Proteomics.

Background: Aging is characterized by the gradual loss of physiological integrity, resulting in impaired function and easier death. This deterioration is a major risk factor for major human pathological diseases, including cancer, diabetes, cardiovascular disease and neurodegenerative diseases. It is very important to find biomarkers that can prevent aging. Methods: Q-Exactive-MS was used for proteomic detection of young and senescence fibroblast. The key senescence-related molecules (SRMs) were identified by integrating transcriptome and proteomics from aging tissue/cells, and the correlation between these differentially expressed genes and well-known aging-related pathways. Next, we validated the expression of these molecules using qPCR, and explored the correlation between them and immune infiltrating cells. Finally, the enriched pathways of the genes significantly related to the four differential genes were identified using the single cell transcriptome. Results: we first combined proteomics and transcriptome to identified four SRMs. Data sets including GSE63577, GSE64553, GSE18876, GSE85358, and qPCR confirmed that ETF1, PLBD2, ASAH1, and MOXD1 were identified as SRMs. Then the correlation between SRMs and aging-related pathways was excavated and verified. Next, we verified the expression of SRMs at the tissue level and qPCR, and explored the correlation between them and immune infiltrating cells. Finally, at the single-cell transcriptome level, we verified their expression and explored the possible pathway by which they lead to aging. Briefly, ETF1 may affect the changes of inflammatory factors such as IL-17, IL-6, and NFKB1 by indirectly regulating the enrichment and differentiation of immune cells. MOXD1 may regulate senescence by affecting the WNT pathway and changing the cell cycle. ASAH1 may affect development and regulate the phenotype of aging by affecting cell cycle-related genes. Conclusion: In general, based on the analysis of proteomics and transcriptome, we identified four SRMs that may affect aging and speculated their possible mechanisms, which provides a new target for preventing aging, especially skin aging.

Phylogenetic analysis of combined mitochondrial genome and 32 nuclear genes provides key insights into molecular systematics and historical biogeography of Asian warty newts of the genus Paramesotriton (Caudata: Salamandridae).

The Paramesotriton Chang, 1935 genus of Asian warty newts is the second most diverse genus in the family Salamandridae, currently containing 14 recognized species from northern Vietnam to southwest-central and southern China. Although species of this genus have been included in previous phylogenetic studies, the origin and interspecific relationships of the genus are still not fully resolved, especially at key nodes in the phylogeny. In this study, we sequenced mitochondrial genomes and 32 nuclear genes from 27 samples belonging to 14 species to reconstruct the interspecific phylogenetic relationships within Paramesotriton and explore its historical biogeography in southern China. Both Bayesian inference and maximum-likelihood analyses highly supported the monophyly of Paramesotriton and its two recognized species groups ( P. caudopunctatus and P. chinensis groups) and further identified five hypothetical phylogenetic cryptic species. Biogeographic analyses indicated that Paramesotriton originated in southwestern China (Yunnan-Guizhou Plateau/South China) during the late Oligocene. The time of origin of Paramesotriton corresponded to the second uplift of the Himalayan/Qinghai-Xizang (Tibetan) Plateau (QTP), rapid lateral extrusion of Indochina, and formation of karst landscapes in southwestern China. Principal component analysis (PCA), independent sample t-tests, and niche differentiation using bioclimatic variables based on locations of occurrence suggested that Paramesotriton habitat conditions in the three current regions (West, South, and East) differ significantly, with different levels of climatic niche differentiation. Species distribution model (SDM) predictions indicated that the most suitable distribution areas for the P. caudopunctatus and P. chinensis species groups are western and southern/eastern areas of southern China. This study increases our knowledge of the taxonomy, biodiversity, origin, and suitable distribution areas of the genus Paramesotriton based on phylogenetic, biogeographic, and species distribution models.

A Novel, Rapid Screening Technique for Sugar Syrup Adulteration in Honey Using Fluorescence Spectroscopy.

The adulteration of honey with different sugar syrups is common and difficult to detect. To ensure fair trade and protect the interests of apiarists, a rapid, simple and cost-effective detection method for adulterants in honey is needed. In this work, fluorescence emission spectra were obtained for honey and sugar syrups between 385 and 800 nm with excitation at 370 nm. We found substantial differences in the emission spectra between five types of honey and five sugar syrups and also found differences in their frequency doubled peak (FDP) intensity at 740 nm. The intensity of the FDP significantly declined (p < 0.01) when spiking honey with ≥10% sugar syrup. To validate this method, we tested 20 adulterant-positive honey samples and successfully identified 15 that were above the limit of detection. We propose that fluorescence spectroscopy could be broadly adopted as a cost-effective, rapid screening tool for sugar syrup adulteration of honey through characterization of emission spectra and the intensity of the FDP.

The complete mitochondrial genome of the Great evening bat Ia io (Chiroptera: Vespertiilionidae) from karst area, Southwestern China.

In this study, the complete mitochondrial genome of Ia io from Guizhou Province, China. The genome was a circular mitochondrial genome of 16689 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and a control region. The average base composition is 32.76% A, 24.59% C, 14.49% G, and 28.16% T. The first complete mitochondrial genome of I. io provides fundamental data for future systematic taxonomic studies of the genus Ia.

Multi-Transcriptomic Analysis and Experimental Validation Implicate a Central Role of STAT3 in Skin Barrier Dysfunction Induced Aggravation of Rosacea.

Objective: Rosacea is a chronic inflammatory skin disease with high morbidity. Previous studies have described the contribution of skin barrier dysfunction (SBD) in the progression of rosacea, but the specific mechanism remains unclear. In this study, we aim to investigate the key genes that may involve SBD-mediated rosacea aggravation. Methods: In this study, we evaluated the SBD patterns of rosacea based on the expression of 23 skin barrier-related genes (SBRGs) using a consensus clustering analysis, and revealed the SBD-mediated immune cells infiltration in rosacea using GSE65914 dataset. The key genes associated with SBD and rosacea progression were identified using WGCNA analysis and then verified in rosacea mice model. Results: Two distinct SBD patterns (moderate- and high-SBD patterns) were determined in rosacea. GO, KEGG and GSEA analysis revealed the differently immune-related signal pathways between two SBD patterns in rosacea. The XCell immune cell assays showed that the increased immune infiltration with SBD. Subsequently, the WGCNA analysis identified STAT3 as the hub gene related to rosacea and SBD, and correlation analysis revealed that STAT3 could contribute to the progression of rosacea partly by dysregulating immune infiltration via activating the cytokine/chemokines signal. Finally, the up-regulated STAT3 was verified in the epidermis of rosacea tissues and correlated with SBRGs expression using IHC and epidermal transcriptome data of rosacea. The vivo experiment showed that tape stripping-induced SBD evidently induced the expression of STAT3 and increased CD4+ T cell infiltration in LL37-induced rosacea-like skin lesion in mice. Conclusion: In conclusion, our results showed that the destruction of the skin barrier aggravates the inflammation levels and immune infiltration of rosacea partly by activating STAT3-mediated cytokine signal pathways in keratinocytes.