[CT-Like MRI and Calcium-Suppressed Spectral CT Imaging of Multifocal Bone Infarcts in Both Lower Extremities:Report of One Case].

Bone infarction has a low incidence in clinical practice and mostly occurs in the metaphysis and diaphysis.Few studies report the advanced imaging technique for bone infarction.Here we reported the fast field echo resembling a CT using restricted echo-spacing and calcium-suppressed spectral CT imaging for a case of multifocal bone infarcts in both lower extremities,aiming to provide diagnostic experience for clinical practice.

CsiLAC4 modulates boron flow in Arabidopsis and Citrus via high-boron-dependent lignification of cell walls.

The mechanisms underlying plant tolerance to boron (B) excess are far from fully understood. Here we characterized the role of the miR397-CsiLAC4/CsiLAC17 (from Citrus sinensis) module in regulation of B flow. Live-cell imaging techniques were used in localization studies. A tobacco transient expression system tested modulations of CsiLAC4 and CsiLAC17 by miR397. Transgenic Arabidopsis were generated to analyze the biological functions of CsiLAC4 and CsiLAC17. CsiLAC4's role in xylem lignification was determined by mRNA hybridization and cytochemistry. In situ B distribution was analyzed by laser ablation inductively coupled plasma mass spectrometry. CsiLAC4 and CsiLAC17 are predominantly localized in the apoplast of tobacco epidermal cells. Overexpression of CsiLAC4 in Arabidopsis improves the plants' tolerance to boric acid excess by triggering high-B-dependent lignification of the vascular system's cell wall and reducing free B content in roots and shoots. In Citrus, CsiLAC4 is expressed explicitly in the xylem parenchyma and is modulated by B-responsive miR397. Upregulation of CsiLAC4 in Citrus results in lignification of the xylem cell walls, restricting B flow from xylem vessels to the phloem. CsiLAC4 contributes to plant tolerance to boric acid excess via high-B-dependent lignification of cell walls, which set up a 'physical barrier' preventing B flow.

First Report of Sanqi (Panax notoginseng) Root Rot Caused by Pythium vexans in China.

Sanqi (Panax notoginseng (Burk.) F. H. Chen) is a precious traditional Chinese herbal medicine. During April of 2021, a root rot disease with approximate 15% incidence was observed on 2-year-old Sanqi plants in a field of Zhouning (27º12' N, 119°33' E), Fujian Province of China. The disease symptoms included severe stunting, leaf chlorosis, root rotting and necrosis, as the disease progressed, the whole plant gradually wilted and died. To recover the causal agent, symptomatic roots were excised, surface sterilized in 75% alcohol for 1.5 min, rinsed in sterilized water three times, dried, and placed on PARP selective medium (Jeffers and Martin 1986), and incubated at 20°C in dark. After 5 days, total of 26 Pythium-like isolates were obtained, and one representative isolate Py21-6 (available from the Institute of Plant Protection, Fujian Academy of Agricultural Sciences) was selected for further identification. Colonies of Py21-6 on PARP plate were white with dense, cottony, aerial, and transparent mycelia. Sporangia were terminal or intercalary, non-papillate, spherical, pyriform or ovoid, measuring 21.7 ± 2.8 × 19.3 ± 2.3 µm (n = 30). Zoospores were saucer-like, released out of sporangium after maturation, and dispersed quickly by swimming. Oogonia were spherical, terminal or occasionally intercalary. Oospores were globose, smooth and aplerotic. The dimensions of zoospores, oogonia, and oospores were 6.8 ± 0.7 µm, 21.6 ± 2.2 µm and 18.2 ± 2.7 µm (n = 30), respectively. Antheridia were bell-shaped or irregular, terminal, monoclinous, and usually one per oogonium. According to the morphological characteristics the isolate was initially identified as Pythium spp. (Van der Plaats-Niterink 1981, Yong et al. 2016). For further identification, DNA extracted from Py21-6, the cytochrome c oxidase subunit I (COI) gene and internal transcribed spacer (ITS) region were amplified and sequenced with primers FM55/FM52R (Long et al. 2012) and ITS1 /ITS4 (White et al. 1990), respectively. BLAST analysis of 680-bp COI (OM688194) and 728-bp ITS (OM663703) sequences revealed 99.86% and 99.99% similarity to Pythium vexans in GenBank (HQ708995 [COI], GU133572 [ITS]). Therefore, the pathogen was identified as P. vexans. In order to fulfill Koch's postulates, isolate Py21-6 was grown on Martin's liquid medium (Martin 1992) for 72 h to produce a spore suspensions of 106 oospores/ml, and the pathogenicity test was conducted by root-dip method. Three groups of 2-year-old Sanqi (15 plants per group) with root soaked for 20 min in oospore suspension were used for pathogenicity, and the other three groups (15 plants per group) with root dipped in sterilized water as control. All treated plants were replanted in (15-cm-diameter) pots (2 plants/pot) filled with mixture of sterilized soil: vermiculite: pearlite (2:1:1, v/v), maintained in greenhouse under 60% black shade cloth at 20 to 26°C with 80% relative humidity, and watered once every three days. After 21days, all inoculated plants showed the same symptoms observed on the original diseased plants in the field, whereas, the control plants remained symptomless. The same pathogen was successfully re-isolated from the inoculated plants, and identical to those of the originals based on morphological and sequence data. To our knowledge, this is the first report of P. vexans causing root rot on Sanqi in China (Farr and Rossman 2022). Root rot is one of the destructive diseases in Sanqi production, identification of the pathogen will be useful to develop effective field management strategies to control this disease.

[Reproducibility Analysis of Iodine Concentrations of Abdominal Parenchymal Organs Based on Spectral CT].

Objective To investigate the intra-and inter-observer reproducibility of iodine concentrations of abdominal parenchymal organs based on spectral CT.Methods The water-free iodine images of the venous phase were retrospectively obtained from 50 patients with abdominal dynamic spectral CT scans.The iodine concentrations were measured in the left,right and caudate lobes of liver,spleen,pancreas and bilateral kidneys.Intraclass correlation coefficient(ICC)and Bland-Altman plot were employed to analyze the intra-and inter-observer reproducibility.Results The intra-observer ICCs of the left,right and caudate lobes of liver,spleen,pancreas,and left and right kidneys were 0.938(0.894,0.965),0.932(0.884,0.961),0.939(0.895,0.965),0.947(0.909,0.970),0.912(0.851,0.949),0.946(0.906,0.969)and 0.907(0.842,0.946),which indicated good intra-observer reproducibility.The inter-observer ICCs of the left,right and caudate lobes of liver,spleen,pancreas,and left and right kidneys were 0.947(0.909,0.970),0.927(0.875,0.958),0.943(0.902,0.968),0.956(0.924,0.975),0.934(0.887,0.962),0.927(0.875,0.958)and 0.892(0.818,0.937),which indicated good inter-observer reproducibility.Bland-Altman plots presented that more than 95% points of the intra-observer differences located within 95% CI of limits of agreement for the caudate lobe of liver,spleen,pancreas and bilateral kidneys,which was same as inter-observer differences of the caudate lobe of liver,spleen and right kidney.Conclusion The iodine concentration measurement based on the spectral CT presented good intra-and inter-observer reproducibility for the caudate lobe of liver and spleen.

[Optimal Mono-energy in Mono-energetic Spectral Computed Tomography of Enhanced Renal Cortex in Cortical Phase Based on Iodine Concentration].

Objective To identify the optimal mono-energetic enhanced spectral CT for renal cortex in cortical phase based on the iodine concentration. Methods Fifty patients with normal renal function received the abdominal enhanced spectral CT examination.The iodine concentration and CT values of the multiple mono-energetic spectral images were measured on renal cortex in cortical phase,and the correlation between the iodine concentration and the CT values and the coefficient of variation(CV)were analyzed. Results The correlation analysis demonstrated that the correlation coefficient was 0.994,0.994,0.993,0.987,0.976,0.960,and 0.938 between mono-energetic spectral CT images(40-100 keV with interval 10 keV,respectively)and iodine concentration(all P <0.001).The correlation coefficients of 40 keV,50 keV(P=0.007)and 60 keV(P=0.030)were significantly higher compared with that of 70 keV,and the correlation coefficients were not significantly among 40 keV,50 keV and 60 keV(P =0.590).The CV of renal cortex in cortical phase was 0.21,0.20,and 0.19 for 40 keV,50 keV,and 60 keV,respectively. Conclusion 60 keV is the optimal mono-energy for the enhanced spectral CT of the renal cortex in cortical phase.

Long non-coding RNA miR143HG predicts good prognosis and inhibits tumor multiplication and metastasis by suppressing mitogen-activated protein kinase and Wnt signaling pathways in hepatocellular carcinoma.

AIM: The expression of microRNA143HG (miR143HG) was significantly downregulated in hepatocellular carcinoma (HCC) tissues by bioinformatics analysis. This study aimed to determine the role of miR143HG in HCC cell proliferation and metastasis. METHODS: Fifty patients with HCC were divided into two groups based on median miR143HG expression levels. The correlation between miR143HG expression and prognosis, and the correlations between miR143HG expression and the patients' clinicopathological characteristics were evaluated based on the two groups. Gain-of-function and loss-of-function measurements of miR143HG were carried out to verify the biological function of miR143HG by Cell Counting Kit-8, EdU, Transwell, and western blotting assays and flow cytometric analysis. The underlying mechanism was explored by quantitative real-time polymerase chain reaction of miRNA (miR-155-5p and miR-26b-5p), luciferase reporter assay, western blotting of Wnt signaling pathway-related proteins (ß-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3ß (GSK3ß), ZEB1, and E-cadherin), mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (extracellular signal-regulated kinase [ERK]1/2, p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, P38, and p-P38), and immunofluorescence staining of ß-catenin. RESULTS: miR143HG expression was markedly downregulated in HCC tissues and cells. Its expression was associated with the presence or absence of portal vein tumor thrombus, hepatitis B virus infection, relapse and metastasis, and Barcelona Clinic Liver Cancer stage. Additionally, miR143HG expression predicted a good prognosis and acted as an independent prognostic factor in HCC for overall survival. Overexpression of miR143HG suppressed HCC cell proliferation and metastasis, and induced cell cycle arrest and apoptosis. Consistently, the depletion of miR143HG resulted in the opposite phenomenon of the aforementioned results. miR143HG inhibits miR-155 expression; miR-155 directly targets APC, which is a negative regulator of the Wnt/ß-catenin pathway, so miR143HG can act on the Wnt pathway. miR143HG was further found to reduce the expression of ß-catenin and block the nuclear accumulation of ß-catenin, ultimately inhibiting the activation of the Wnt pathway. It inhibits the expression of Wnt downstream target gene ZEB1, and then E-cadherin expression is increased and cell motility is inhibited. Furthermore, miR143HG exerts its antiproliferative function by influencing the MAPK signaling pathway and then inducing G2 /M arrest in cells. CONCLUSION: This study showed that miR143HG plays critical roles in the development and progression of HCC by suppressing the MAPK and Wnt signaling pathways.

Deep-Fried Atractylodis Rhizoma Protects against Spleen Deficiency-Induced Diarrhea through Regulating Intestinal Inflammatory Response and Gut Microbiota.

According to the theories of traditional Chinese medicine, spleen deficiency often leads to diarrhea, and deep-fried Atractylodis Rhizoma (DAR) is commonly used for the treatment. However, the association between spleen deficiency and diarrhea remains unclear. The present study aimed to investigate the therapeutic effect of DAR for the treatment of diarrhea caused by spleen deficiency and analyze the related mechanisms. It was found that a high dose group of an ethanolic extract of deep-fried Atractylodis Rhizoma (EEDAR-H) significantly inhibited weight loss, diarrhea, and pathological changes in colon tissue induced by rhubarb. EEDAR-H was found to significantly reduce the level of intestinal inflammatory cytokines and increase the expression of gastrointestinal motility hormones. In addition, EEDAR-H significantly increased the expression of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) and restored abnormal water metabolism; Shen-Ling-Bai-Zhu-San (SLBZS) induced the same effect as EEDAR-H. Additional tests on the mechanism found that EEDAR-H and SLBZS promoted the integrity of the intestinal barrier. Both significantly increased the expression of the tight junction protein ZO-1 and Occludin, inhibited the phosphorylation of p38MAPK and MLC, and significantly reduced the expression levels of PAR-2. Analysis of the gut microbiota indicated that overall changes in its structure were reversed after treatment with EEDAR-H or SLBZS, in addition to significant modulation of the abundance of different phyla. At the genus level, EEDAR-H or SLBZS significantly reduced the levels of potential pathogens and increased those of beneficial bacteria.

MicroRNA Sequencing Revealed Citrus Adaptation to Long-Term Boron Toxicity through Modulation of Root Development by miR319 and miR171.

Boron (B) toxicity in Citrus is a common physiological disorder leading to reductions in both productivity and quality. Studies on how Citrus roots evade B toxicity may provide new insight into plant tolerance to B toxicity. Here, using Illumina sequencing, differentially expressed microRNAs (miRNAs) were identified in B toxicity-treated Citrus sinensis (tolerant) and C. grandis (intolerant) roots. The results showed that 37 miRNAs in C. grandis and 11 miRNAs in C. sinensis were differentially expressed when exposed to B toxicity. Among them, miR319, miR171, and miR396g-5p were confirmed via 5'-RACE and qRT-PCR to target a myeloblastosis (MYB) transcription factor gene, a SCARECROW-like protein gene, and a cation transporting ATPase gene, respectively. Maintenance of SCARECROW expression in B treated Citrus roots might fulfill stem cell maintenance, quiescent center, and endodermis specification, thus allowing regular root elongation under B-toxic stress. Down-regulation of MYB due to up-regulation of miR319 in B toxicity-treated C. grandis roots might decrease the number of root tips, thereby dramatically changing root system architecture. Our findings suggested that miR319 and miR171 play a pivotal role in Citrus adaptation to long-term B toxicity by targeting MYB and SCARECROW, respectively, both of which are responsible for root growth and development.

MRI Histogram Texture Feature Analysis of the Optic Nerve in the Patients with Optic Neuritis.

Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging (T2WI) with fat saturation and enhanced T1 weighted imaging (T1WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2WI images. The normal optic nerve (NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic (ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement (ONwEN), affected optic nerve without enhancement (ONwoEN), contralateral normal appearing optic nerve (NAON) and NON.Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN (both P=0.000), ONwEN vs. NON (both P=0.000) and NAON vs. NON (both P<0.05). ROC analysis demonstrated that the area under the curve (AUC) of histogram texture Energy were 0.758, 0.795 and 0.701 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON, AUC of Entropy were 0.758, 0.795 and 0.707 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON.Conclusions The altered MRI histogram texture Energy and Entropy could be considered as a surrogate for MRI enhancement to evaluate the involved optic nerve and normal-appearing optic nerve in optic neuritis.

Molluscicidal activity and physiological toxicity of Macleaya cordata alkaloids components on snail Oncomelania hupensis.

In order to search new local plant molluscicides for the control of the vectors of schistosomiasis, leaves of Macleaya cordata (Willd) R. Br. were used to extract and separate alkaloid components by thinner acid method and column chromatography, and the molluscicidal effect of alkaloid components against snail Oncomelania hupensis was determined by bioassay. The results showed that 7 alkaloid components (AN1-7) were obtained after extracting and separating alkaloids from the leaves of M. cordata, where AN2 was found being the most toxic against snail O. hupensis with 48h LC50 and LC90 values of AN2 of 6.35mg/L and 121.23mg/L, respectively. Responses of some critical enzymes to AN2, including activities of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate transaminase (AST), Malic dehydrogenase (MDH) and Succinate dehydrogenase (SDH) in both cephalopodium and liver, were also detected through experiments, which also explored esterase isozyme (EST) exposed to AN2 in liver tissue. The results showed that AN2 significantly inhibited the activities of SDH, MDH and esterase isozyme, as AN2 significantly stimulated the activities of ALP, ALT and AST to increase at a low concentration (e.g. 25mg/L), while significantly inhibited the activities of these enzymes at a high concentration (100mg/L). These results indicated that AN2 not only inhibited protein synthesis, and respiratory chain oxidative phosphorylation, but also caused hepatocellular injury and reduced the detoxification ability of liver.

Global Profiling and Novel Structure Discovery Using Multiple Neutral Loss/Precursor Ion Scanning Combined with Substructure Recognition and Statistical Analysis (MNPSS): Characterization of Terpene-Conjugated Curcuminoids in Curcuma longa as a Case Study.

To fully understand the chemical diversity of an herbal medicine is challenging. In this work, we describe a new approach to globally profile and discover novel compounds from an herbal extract using multiple neutral loss/precursor ion scanning combined with substructure recognition and statistical analysis. Turmeric (the rhizomes of Curcuma longa L.) was used as an example. This approach consists of three steps: (i) multiple neutral loss/precursor ion scanning to obtain substructure information; (ii) targeted identification of new compounds by extracted ion current and substructure recognition; and (iii) untargeted identification using total ion current and multivariate statistical analysis to discover novel structures. Using this approach, 846 terpecurcumins (terpene-conjugated curcuminoids) were discovered from turmeric, including a number of potentially novel compounds. Furthermore, two unprecedented compounds (terpecurcumins X and Y) were purified, and their structures were identified by NMR spectroscopy. This study extended the application of mass spectrometry to global profiling of natural products in herbal medicines and could help chemists to rapidly discover novel compounds from a complex matrix.

Comprehensive chemical analysis of the rhizomes of Drynaria fortunei by orthogonal pre-separation and liquid chromatography mass spectrometry.

The chemical composition of Drynaria fortunei, a traditional Chinese herbal medicine, is very complicated. In order to separate these chemicals to obtain their structural information, an orthogonal sample enrichment procedure was established. The ethyl acetate extract of D. fortunei was pre-separated by Sephadex LH-20 × polyamide columns to yield 15 fractions. These fractions were analyzed successively using a reversed-phase Agilent Zorbax SB-C18 column, coupled with diode array detection and electrospray ionization tandem mass spectrometry. The method reduced co-elution and enriched minor compounds on the basis of their chemical features. A total of 369 compounds were detected by LC/MSn, compared to less than 50 compounds without pre-separation. The pretreatment facilitated the analytical separation of flavonoids, proanthocyanidins, triterpenoids, phenolic acids, and lignans in D. fortunei, and allowed a comprehensive chemical profiling of these constituents. This method could be applied to other multicomponent herbal extracts.

Simultaneous determination of five minor coumarins and flavonoids in Glycyrrhiza uralensis by solid-phase extraction and high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

Minor phenolic compounds in licorice (Glycyrrhiza uralensis) have recently been proved for diverse bioactivities and favorable bioavailability, indicating that they may play an important role in the therapeutic effects or herb-drug interactions of licorice. However, so far, their abundance in licorice remains unknown. In this study, a reliable solid-phase extraction coupled with a high-performance liquid chromatography and diode array detection method was established to determine the minor phenolic compounds in licorice. The analytes were enriched by a three-step solid-phase extraction method, and then separated on a YMC ODS-A column by gradient elution. Five coumarins and flavonoids were identified by electrospray ionization tandem mass spectrometry, and then quantified using high-performance liquid chromatography and diode array detection. The amounts of glycycoumarin, dehydroglyasperin C, glycyrol, licoflavonol, and glycyrin in G. uralensis were 0.81 ± 0.28, 1.25 ± 0.59, 0.20 ± 0.08, 0.12 ± 0.04, and 0.17 ± 0.08 mg/g, respectively. Abundances of these compounds in other Glycyrrhiza species (G. glabra, G. inflata, and G. yunnanesis) were remarkably lower than G. uralensis.

Gene signatures of endoplasmic reticulum stress and mitophagy for prognostic risk prediction in lung adenocarcinoma.

Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up-regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5-, 3-, and 1-year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p < 0.001), suggesting it might be a critical gene for LUAD prognosis prediction. Overall, the prognosis model based on ERS and mitophagy genes in LUAD can be useful for evaluating the prognosis of patients with LUAD, and VDAC1 may serve as a promising biomarker for LUAD prognosis.

The multi-slit very small angle neutron scattering instrument at the China Spallation Neutron Source.

A multi-slit very small angle neutron scattering (MS-VSANS) instrument has been finally accepted at the China Spallation Neutron Source (CSNS). It is the first spallation neutron source based VSANS instrument. MS-VSANS has a good signal-to-noise ratio and can cover a wide scattering vector magnitude range from 0.00028 to 1.4 Å-1. In its primary flight path, a combined curved multichannel beam bender and sections of rotary exchange drums are installed to minimize the background downstream of the instrument. An exchangeable multi-slit beam focusing system is integrated into the primary flight path, enabling access to a minimum scattering vector magnitude of 0.00028 Å-1. MS-VSANS has three modes, namely conventional SANS, polarizing SANS and VSANS modes. In the SANS mode, three motorized high-efficiency 3He tube detectors inside the detector tank cover scattering angles from 0.12 to 35° simultaneously. In the polarizing SANS mode, a double-V cavity provides highly polarized neutrons and a high-efficiency 3He polarization analyser allows full polarization analysis. In the VSANS mode, an innovative high-resolution gas electron multiplier detector covers scattering angles from 0.016 to 0.447°. The absolute scattering intensities of a selection of standard samples are obtained using the direct-beam technique; the effectiveness of this method is verified by testing the standard samples and comparing the results with those from a benchmark instrument. The MS-VSANS instrument is designed to be flexible and versatile and all the design goals have been achieved.

Cage-rearranged and cage-intact syntheses of azido-functionalized larger T10 and T12 POSSs.

Herein, we investigate the product type and distribution during the synthesis of azido-functionalized larger polyhedral oligomeric silsesquioxanes (POSSs) using 3-chloropropyl- and chloromethyldimethylsilylethyl-functionalized T8, T10, and T12 POSSs as precursors. Our findings indicate that cage rearrangement occurs for the 3-chloropropyl-functionalized POSS cages with a stability order of T12 > T10 > T8, while the chloromethyldimethylsilylethyl-functionalized POSS cages remain structurally intact after the nucleophilic substitution.

Association between per- and polyfluoroalkyl substances exposure and prevalence of chronic obstructive pulmonary disease: The mediating role of serum albumin.

BACKGROUND: No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship. METHODS: This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin. RESULTS: Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR males: 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR females: 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR males: 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR females: 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P interaction: <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P nonlinear:0.001), ln-PFNA (P nonlinear:0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %). CONCLUSION: This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms.

The feasibility of using pathobiome strains as live biotherapeutic products for human use.

The evaluation of pathobiome strains should be conducted at the strain level, involving the identification of the functional genes, while considering the impact of ecological niche and drug interactions. The safety, efficacy, and quality management of live biotherapeutic products (LBPs), especially pathobiome strains, have certain peculiarities. Promising development methods include the recombinant LBP and active metabolites.

The value of urinary exosomal microRNA-21 in the early diagnosis and prognosis of bladder cancer.

Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

The fine temporal structure of the rat licking pattern: what causes the variabiliy in the interlick intervals and how is it affected by the drinking solution?

Licking is a repetitive behavior controlled by a central pattern generator. Even though interlick intervals (ILIs) within bursts of licks are considered fairly regular, the conditions that affect their variability are unknown. We analyzed the licking pattern in rats that licked water, 10% sucrose solution, or 10% ethanol solution, in 90-min recording sessions after 4h of water deprivation. The histograms of ILIs indicate that licking typically occurred at a preferred ILI of about 130-140ms with evidence of bimodal or multimodal distributions due to occasional licking failures. We found that the longer the pause between bursts of licks, the shorter was the first ILI of the burst. When bursts of licks were preceded by a pause >4 s, the ILI was the shortest (~110ms) at the beginning of the burst, and then it increased rapidly in the first few licks and slowly in subsequent licks. Interestingly, the first ILI of a burst of licks was not significantly different when licking any of the 3 solutions, but subsequent licks exhibited a temporal pattern characteristic of each solution. The rapid deceleration in intraburst licking rate was due to an increase from ~27ms to ~56ms in the tongue-spout contact duration while the intercontact interval was only slightly changed (80-90ms). Therefore, the contact duration seems to be the major factor that increases the variability in the ILIs and could be another means for the rat to adjust the amount of fluid ingested in each individual lick.