Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

The role of microbiome: a novel insight into urolithiasis.

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

Engineering Isopropanol Dehydrogenase for Efficient Regeneration of Nicotinamide Cofactors.

Isopropanol dehydrogenase (IPADH) is one of the most attractive options for nicotinamide cofactor regeneration due to its low cost and simple downstream processing. However, poor thermostability and strict cofactor dependency hinder its practical application for bioconversions. In this study, we simultaneously improved the thermostability (433-fold) and catalytic activity (3.3-fold) of IPADH from Brucella suis via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H) by 1.23 × 106-fold. When these variants were employed in three typical bioredox reactions to drive the synthesis of important chiral pharmaceutical building blocks, they outperformed the commonly used cofactor regeneration systems (glucose dehydrogenase [GDH], formate dehydrogenase [FDH], and lactate dehydrogenase [LDH]) with respect to efficiency of cofactor regeneration. Overall, our study provides two promising IPADH variants with complementary cofactor specificities that have great potential for wide applications. IMPORTANCE Oxidoreductases represent one group of the most important biocatalysts for synthesis of various chiral synthons. However, their practical application was hindered by the expensive nicotinamide cofactors used. Isopropanol dehydrogenase (IPADH) is one of the most attractive biocatalysts for nicotinamide cofactor regeneration. However, poor thermostability and strict cofactor dependency hinder its practical application. In this work, the thermostability and catalytic activity of an IPADH were simultaneously improved via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H). The resultant variants show great potential for regeneration of nicotinamide cofactors, and the engineering strategy might serve as a useful approach for future engineering of other oxidoreductases.

A High-Throughput Screening Method for the Directed Evolution of Hydroxynitrile Lyase towards Cyanohydrin Synthesis.

Chiral cyanohydrins are useful intermediates in the pharmaceutical and agricultural industries. In nature, hydroxynitrile lyases (HNLs) are a kind of elegant tool for enantioselective hydrocyanation of carbonyl compounds. However, currently available methods for demonstrating hydrocyanation are still stalled at precise, but low-throughput, GC or HPLC analyses. Herein, we report a chromogenic high-throughput screening (HTS) method that is feasible for the cyanohydrin synthesis reaction. This method was highly anti-interference and sensitive, and could be used to directly profile the substrate scope of HNLs either in cell-free extract or fermentation clear broth. This HTS method was also validated by generating new variants of PcHNL5 that presented higher catalytic efficiency and stronger acidic tolerance in variant libraries.

Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an incurable cancer resistant to traditional treatments, although a limited number of early-stage patients can undergo radical resection. Immunotherapies for the treatment of haematological malignancies as well as solid tumours have been substantially improved over the past decades, and impressive results have been obtained in recent preclinical and clinical trials. However, PDAC is likely the exception because of its unique tumour microenvironment (TME). In this review, we summarize the characteristics of the PDAC TME and focus on the network of various tumour-infiltrating immune cells, outlining the current advances in PDAC immunotherapy and addressing the effect of the PDAC TME on immunotherapy. This review further explores the combinations of different therapies used to enhance antitumour efficacy or reverse immunodeficiencies and describes optimizable immunotherapeutic strategies for PDAC. The concordant combination of various treatments, such as targeting cancer cells and the stroma, reversing suppressive immune reactions and enhancing antitumour reactivity, may be the most promising approach for the treatment of PDAC. Traditional treatments, especially chemotherapy, may also be optimized for individual patients to remodel the immunosuppressive microenvironment for enhanced therapy.

Analysis on the polymorphisms of site RS4977574, and RS1333045 in region 9p21 and the susceptibility of coronary heart disease in Chinese population.

BACKGROUND: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. METHODS: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. RESULTS: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. CONCLUSIONS: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Zygomatic Nonunion: A Misunderstood Complication of Reduction Malarplasty.

Reduction malarplasty is a popular facial skeletal contour surgery in East Asia. Zygomatic nonunion is a reported complication. However, it is often misunderstood and misdiagnosed. Here we present typical misdiagnosed zygomatic nonunion cases, propose and preliminarily clarify 4 major misunderstandings of zygomatic nonunion: diagnostic standard, the cause, the incidence, and the prognosis of zygomatic nonunion.

Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography.

BACKGROUND: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. METHODS: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31-84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. RESULTS: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p<0.05) than those in patients with lower scores. Multiple linear regression analysis indicated that the average coronary artery diameter was significantly associated with the Gensini score (ß=-0.444, p<0.00001). Moreover, the diameters of the coronary arteries were potential predictors of CAD, with areas under the receiver operating characteristic curves of 0.268 for average diameter (95% confidence interval [CI]: 0.183-0.353, p<0.00001), 0.356 for the LM diameter (95% CI: 0.266-0.445, p=0.005), 0.214 for the LAD diameter (95% CI: 0.136-0.291, p<0.00001), 0.366 for the LCX diameter (95% CI: 0.271-0.461, p=0.009), and 0.346 for the RCA diameter (95% CI: 0.245-0.447, p=0.003). CONCLUSION: The diameters of coronary arteries are inversely associated with the severity of CAD.

Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China.

BACKGROUND: Differences in microRNA (miRNA) profiles between patients with and without coronary heart disease (CHD)have not been fully determined. The purpose of the study was to evaluate in a multi-ethnic population in China the predictive value of miRNAs previously suggested to have a role in CHD. SUBJECT AND METHOD: 932 participants were included, and plasma samples obtained. A quantitative reverse-transcription PCR(RT-qPCR) assay was conducted to confirm the concentration of plasma miRNAs. Circulating levels of miRNAs were quantified using the 2-Δct method. The severity of coronary atherosclerosis was evaluated via Gensini Scores. RESULT: The circulating levels of the nine proposed miRNAs were not different among the five main ethnicities examined (all p > 0.05). The Spearman correlation analyses indicated that miR-221 and miR-130a were negatively associated with the severity of CHD as indicated by Gensini Scores (r = -0.106, p = 0.001;r = -0.073, p = 0.026). Results of the univariate analysis showed that lower circulating miR-221 (OR, 1.663; 95 % CI, 1.255-2.202, p = <0.001), miR-155 (OR, 1.520; 95 % CI, 1.132-2.042, p = 0.005), and miR-130a (OR, 1.943; 95% CI, 1.410-2.678, p = <0.001) were potential risk factors for CHD. Moreover, miR-130a (OR, 2.405; 95 % CI, 1.691-3.421, p = <0.001) remained independently associated with the risk of CHD after adjusting for potential confounding factors. The analysis of the possible positive/negative associations between miR-221, miR-155 and miR-130awere conducted. A positive association between miR-130a and miR-155 was found (SI = 1.60, SIM = 1.21 and AP = 0.22), and in these groups, the proportion of CHD attributable to the interaction between miR-130a and miR-155 was as high as 22 %. A negative interaction was found between miR-221 and miR-130a (SI = 0.68, SIM = 0.60 and AP = 0.27). CONCLUSION: Plasma levels of miR-221, miR-130a and miR-155 decreased in patients with CHD, and miR-130a may be an independent predictor for CHD.

Synergistic Effect of Lipoprotein-Associated Phospholipase A2 with Classical Risk Factors on Coronary Heart Disease: A Multi-Ethnic Study in China.

AIMS: We evaluated the synergistic effect of lipoprotein-associated phospholipase A2 (Lp-PLA2) in association with classical risk factors in predicting coronary heart disease (CHD) and demonstrated the diagnostic value of Lp-PLA2 for predicting coronary stenotic lesions in subjects with CHD. METHODS: Blood samples were acquired from 911 consecutive adult subjects (662 males and 249 females) from 11 ethnic groups. Lp-PLA2 plasma levels were detected using a commercially available turbidimetric immunoassay (TIA). CHD in patients was confirmed using coronary angiography, and the severity of coronary atherosclerosis was assessed using the Gensini scoring system. RESULTS: A binary logistic regression was performed to analyse the relationships between Lp-PLA2 and other risk factors. A multivariate logistic regression analysis revealed that Lp-PLA2 levels were significantly associated with CHD (OR, 1.882; 95% CI, 1.369-2.587, p=0.000).The area under the receiver operating characteristic curve for Lp-PLA2 was 0.589 (95%CI, 0.549-0.629, p=0.000).The synergism between Lp-PLA2 and other risk factors was also investigated. The proportion of CHD attributable to the interaction between Lp-PLA2 and age was as high as 64%. CONCLUSIONS: Lp-PLA2 levels in human plasma were positively associated with the severity of CHD, and there was a clear positive interaction between Lp-PLA2 and classical risk factors in predicting CHD.

Complex solution chemistry behind the simple "one-pot" synthesis of vanadium-substituted polyoxometalates unraveled by electrospray ionization mass spectrometry.

RATIONALE: The "one-pot" method is a deceptively simple and straightforward method for synthesis of polyoxometalates (POMs). However, the complex solution chemistry behind the simple method is neither clear nor elucidated thoroughly by a suitable method. In general, POM chemists are more focused on what final products are obtained by deliberately choosing the ingredients used in the "one-pot" process with a limited knowledge of what is actually happening in the reaction solution. METHODS: Time-resolved electrospray ionization mass spectrometry (ESI-MS) was developed to monitor the dynamic solution speciation changes occurred in the reaction mixtures ({SiW12-x } (x = 1-3) + NaVO3 ) against reaction time. The reactions were conducted as normal, with 2 µL aliquots removed at specific time intervals during the reaction. The aliquots were immediately diluted with 1 mL of HPLC grade water and then analyzed by ESI-MS. As a control, solutions of each {SiW12-x } were analyzed alongside the vanadium reactions to corroborate which fragments were due to the lacunary precursors and which were due to the reactions with sodium metavanadate. RESULTS: It was discovered that the reaction solution speciation was sensitively changed with the reaction conditions such as concentration, temperature, and reaction time. Spontaneous transformations from mono- into di- and eventually tri-substituted products ({SiW11 V} â†’ {SiW10 V2 } â†’ {SiW9 V3 }) were observed for the reactions of {SiW11 } + VO3 (-) and {SiW10 } + VO3 (-) , respectively. Higher concentration and temperature definitely accelerate the transformation reaction rates whereas different molar ratios of reactants have minimal effects on changing the solution speciation in the cases studied. CONCLUSIONS: Time-resolved ESI-MS is effectively and successfully used in the monitoring of the dynamic speciation changes in the reaction mixtures consisting of lacunary POMs with transition salts. This study will provide guidance for the oriented design and controlled synthesis of POMs with novel structures. Copyright © 2016 John Wiley & Sons, Ltd.

Characterization and expression analysis of Toll-like receptor 2 gene in large yellow croaker, Larimichthys crocea.

Toll-like receptor 2 (TLR2) plays an important role in innate immune responses. Here we describe the isolation and characterization of the full-length cDNA sequence of toll-like receptor 2 in large yellow croaker Larimichthys crocea (LcTLR2). The LcTLR2 cDNA contains a 5'-terminal untranslated region (5'-UTR) of 135 bp, an open reading frame (ORF) of 2478 bp encoding a polypeptide of 825 amino acid residues and a 3'-UTR of 50 bp. Subcellular localization analysis suggested that the LcTLR2-pEGFP was mainly expressed in cytoplasm. Quantitative real-time reverse transcription PCR (qRT-PCR) analysis revealed a broad expression of LcTLR2 in most examined tissues, with the most predominant expression in blood, followed by spleen, and the weakest expression in stomach. The expression levels of LcTLR2 after injection with Vibrio parahaemolyticus, Lipopolysaccharides (LPS) and poly inosinic:cytidylic (polyI:C) were investigated in spleen, head-kidney and liver. Our results showed that LcTLR2 transcripts increased significantly after all the three immune challenges (p < 0.05). However, compared with polyI:C and LPS, higher expression levels of LcTLR2 were induced in all examined tissues after V. parahaemolyticus stimulation. In addition, the expression levels of LcTLR2 after flagellin, polyI:C, peptidoglycan (PGN) and LPS challenge in LCK were investigated, our findings showed that high LcTLR2 transcripts were induced after flagellin and PGN stimulation, suggesting that LcTLR2 might play a vital role in fish defense against bacterial infection. Furthermore, compared with LPS, flagellin and peptidoglycan might play an important role in LcTLR2 induction in large yellow croaker.

Identification and expression profiles of ERK2 and ERK5 in large yellow croaker (Larimichthys crocea) after temperature stress and immune challenge.

Fish is highly affected by many environmental stresses such as temperature and invasive infection. The extracellular signal-regulated kinase (ERK) pathway, part of the mitogen-activated protein kinase (MAPK) family, is found to act as crucial mediators for cell differentiation, proliferation and cell response to various stresses. In the present study, ERK2 (LcERK2) and ERK5 (LcERK2) were cloned and characterized from large yellow croaker, Larimichthys crocea. The full length cDNA sequence of LcERK2 was of 1910 bp, including an ORF of 1110bp encoding a polypeptide of 369 amino acids. The full length cDNA sequence of LcERK5 was of 3720bp, including an ORF of 3375bp encoding a polypeptide of 1124 amino acids. Multiple alignments showed that both LcERK2 and LcERK5 contained highly conserved TEY motif and S_TKc domain in MAPK family and the unique catalytic and active structures of ERK2 and ERK5. Subcellular localization revealed that both LcERK2 and LcERK5 expressed in the cytoplasm and cell nucleus. The expression of LcERK2 and LcERK5 were detected in most tissues of large yellow croaker, with the most predominant expression of LcERK2 in brain and LcERK5 in gill, and the weakest expression of LcERK2 in liver and LcERK5 in intestine, respectively. The expression levels of LcERK2 and LcERK5 after temperature stress and poly I:C and flagellin challenge were investigated in LCK (L. crocea kidney) cells. After temperature stress, significant down-regulations of LcERK2 transcripts were detected after 10 °C stress (p < 0.05) whereas LcERK2 transcripts increased significantly after 35 °C stress (p < 0.05). However, significant down-regulations of LcERK5 expression were detected at most time points after both cold and heat stress (p < 0.05). However, significant up-regulations of LcERK2 and LcERK5 transcripts were found after immune challenge (p < 0.05). Our results showed that LcERK2 transcripts enhanced after heat stress and both LcERK2 and LcERK5 transcripts could be induced by immune challenge. These findings indicated that LcERK2 might be more important in fish response to high temperature stress and both LcERK2 and LcERK5 might play an important role in fish immune response.

Sodium fluoride disrupts DNA methylation of H19 and Peg3 imprinted genes during the early development of mouse embryo.

Sodium fluoride (NaF) is associated with embryonic and fetal development abnormalities, but the mechanism by which this occurs is unclear. DNA methylation, an important epigenetic reprogramming mechanism, is essential for normal embryonic development. Thus, we investigated the effect of NaF on DNA methylation in early mouse embryos, as well as mouse sperm and liver using bisulfite sequencing and ELISA. Data indicate that H19, a paternally imprinted gene, compared to control embryos, was less methylated in 8-cell embryos from pregnant mice treated with NaF (100 mg/l) in drinking water for 48 h. Peg3, a maternally imprinted gene, and the Line1 repeated sequence were similarly methylated in NaF-treated and control embryos. Oral ingestion of NaF for 35 days did not significantly change Line1 and genomic global DNA methylation in the liver. H19, Rasgrf1, Line1, and genomic global DNA methylation were also similar in NaF-treated and control sperm. Female mice mated with NaF-treated male mice (35 days) had less methylated H19, but Peg3 was significantly more methylated. Line1 was similarly methylated in treated 8-cell embryos, compared to control embryos. NaF treatment of male mice before copulation significantly increased the expression of H19 in blastocysts, whereas H19 expression was not detected in 8-cell embryos. Data suggest that NaF may interact directly with the embryo to disrupt the maintenance of normal gene imprinting during pregnancy. Long-term NaF exposure of males may not directly affect DNA methylation of the sperm and liver, but the sperm may signal to early embryos with abnormal gene imprinting.

p38 MAPK involvement in the thermal stress response occurs via HSP27 and caspase3 in the large yellow croaker (Larimichthys crocea).

The p38 mitogen-activated protein kinase (p38 MAPK) is a multifunctional molecule that is involved in cellular response to various stressful stimuli. In the present study, the full-length cDNA sequence of p38 MAPK (Lcp38 MAPK) was identified from the large yellow croaker Larimichthys crocea, which encoded a polypeptide of 361 amino acid residues. The predicted Lcp38 MAPK protein contained a highly conserved Thr-Gly-Tyr (TGY) motif, a glutamate and aspartate (ED) site, a substrate binding site (Ala-Thr-Arg-Trp < ATRW>), and a serine/threonine kinase catalytic (S_TKc) domain characteristic of the MAPK family. The constitutive expression of Lcp38 MAPK was detected in most of the tissues examined with the strongest expression in intestine. Subcellular localization in LCK cells (kidney cell line from a L. crocea) revealed that Lcp38 MAPK existed in both the cytoplasm and cell nucleus. The expression of Lcp38 MAPK after temperature stress was tested in LCK cells. The results indicated that Lcp38 MAPK transcripts were significantly upregulated under both cold (10 °C) and heat stress (35 °C) (P < 0.05). Furthermore, the phosphorylation levels of p38 MAPK as well the transcriptional levels of heat shock protein 27 (HSP27) and caspase3 in LCK cells were significantly induced under thermal exposure (P < 0.05). However, the cold- and heat induced HSP27 and caspase3 expression was significantly suppressed by SB203580, a specific inhibitor of p38-MAPK (P < 0.05). These findings indicated that Lcp38 MAPK might be involved in the cellular stress response via HSP27 and caspase3 in large yellow croaker.

Circular economy strategies in supply chains, enhancing resource efficiency and sustainable development goals.

Eco-industrial parks are the real-world implementation of green supply chain management. There is a growing need to include the circular economy concept into supply chain management as a means of striking a better economic, social, and environmental balance, as the importance of the external sustainability of the supply chain is challenging. Using 357 questionnaires filled out by enterprises in China's eco-industrial parks, we examine the connections and causal relationships between resource efficiency, environmental impact, green supply chain management, and circular economy. To learn how a green supply chain's circular economy affects resource efficiency and environmental performance in the China region, this study makes use of the instrumental variable approach (structure equation model (SEM)). The results of this study indicate that environmentally responsible supply chain management and circular economy have beneficial effects on environmental performance and resource efficiency. The management of the GSC has a negative and small impact on economic performance, although each of the components is a substantial contributor to better performance in the environment. Conclusions from this study will assist those responsible for making decisions within supply chains in developing a plan that is useful for increasing a company's performance along economic and environmental dimensions. This study not only broadens our understanding of the factors that influence green supply chain management but also offers theoretical direction for the implementation of successful green production practices by businesses located in eco-industrial parks.

Laryngeal paraganglioma: The analysis of misdiagnosed cases and literature review.

Laryngeal paraganglioma (LP) is an exceptionally rare neuroendocrine tumor, underscoring importance of accurate identification to preclude misdiagnoses. In this review, we presented two typical misdiagnosed LPs, and offered reviews of LP cases reported over the preceding decade and all documented misdiagnosed LP cases. Furthermore, we systematically investigated the underlying causes of misdiagnosis and elucidated key points for effective differentiation. A retrospective analysis of 28 LP cases revealed a predominant occurrence in middle-aged women, with an average history of 25.1 months. Through an analysis of all misdiagnosed cases (n = 37), supraglottic LPs were frequently misidentified as laryngeal carcinomas and vascular tumors, while subglottic LPs were often misdiagnosed as thyroid cancers. And the occurrence of misdiagnosis resulted in delayed and inappropriate treatments, contributing to the deterioration of LP patients (14 cases, 37.8%). In conclusion, this review endeavored to heighten awareness of LPs, with the ultimate goal of advancing diagnostic precision and enhancing patient outcomes.

Case report: Novel mutations in the SPG11 gene in a case of autosomal recessive hereditary spastic paraplegia with a thin corpus callosum.

A 24-year-old man presented with insidious onset progressive gait disturbance and was finally diagnosed with autosomal recessive hereditary spastic paraplegia. Two novel mutations, including a frameshift mutation (c.5687_5691del) and a non-sense mutation (c.751C>T), were identified in the SPG11 gene of the patient through whole genome sequencing. The frameshift mutation of c.5687_5691del leads to a change in amino acid synthesis beginning with amino acid No. 1896 arginine and terminating at the 8th amino acid after the change (p. Arg1896MetfsTer8). The non-sense mutation (c.751C>T) causes the conversion of codon 251st encoding the amino acid Gln into a stop codon (p. Gln251Ter), resulting in premature termination of peptide synthesis. Although confirmation of compound-heterozygosity could not be performed, our findings enriched the phenotypic spectrum of SPG11 mutations related to hereditary spastic paraplegia.

Identification of Two Clusters in Renal Pelvis Urobiome of Unilateral Stone Formers Using 2bRAD-M.

Urolithiasis is a common urological disease with increasing incidence and a high recurrence rate, whose etiology is not fully understood. The application of sequencing and culturomics has revealed that urolithiasis is closely related to the urinary microbiome (urobiome), shedding new light on the pathogenesis of stone formation. In this study, we recruited 30 patients with unilateral stones and collected their renal pelvis urine from both sides. Then, we performed 2bRAD-M, a novel sequencing technique that provides precise microbial identification at the species level, to characterize the renal pelvis urobiome of unilateral stone formers in the both sides. We first found that the urobiome in the stone side could be divided into two clusters (Stone1 and Stone2) based on distance algorithms. Stone2 harbored higher microbial richness and diversity compared to Stone1. The genera Cupriavidus and Sphingomonas were overrepresented in Stone1, whereas Acinetobacter and Pseudomonas were overrepresented in Stone2. Meanwhile, differential species were identified between Stone1 and Stone2. We further constructed a random forest model to discriminate two clusters which achieved a powerful diagnostic potential. Moreover, the urobiome of the non-stone side (Control1/2) was compared with that of the stone side (Stone1/2). Stone1 and Control1 showed different microbial community distributions, while Stone2 was similar to Control2 based on diversity analysis. We also identified differentially abundant species among all groups. We assumed that there might be different mechanisms of how microbiota contribute to stone formation in two clusters. Our findings might assist in the selection of suitable medical treatments for urolithiasis.