Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease. Although HCM has been reported to be associated with many variants of genes involved in sarcomeric protein biomechanics, pathogenic genes have not been identified in patients with partial HCM. FARS2 (the mitochondrial phenylalanyl-tRNA synthetase), a type of mitochondrial aminoacyl-tRNA synthetase, plays a role in the mitochondrial translation machinery. Several variants of FARS2 have been suggested to cause neurological disorders; however, FARS2-associated diseases involving other organs have not been reported. We identified FARS2 as a potential novel pathogenic gene in cardiomyopathy and investigated its effects on mitochondrial homeostasis and the cardiomyopathy phenotype. METHODS: FARS2 variants in patients with HCM were identified using whole-exome sequencing, Sanger sequencing, molecular docking analyses, and cell model investigation. Fars2 conditional mutant (p.R415L) or knockout mice, fars2-knockdown zebrafish, and Fars2-knockdown neonatal rat ventricular myocytes were engineered to construct FARS2 deficiency models both in vivo and in vitro. The effects of FARS2 and its role in mitochondrial homeostasis were subsequently evaluated using RNA sequencing and mitochondrial functional analyses. Myocardial tissues from patients were used for further verification. RESULTS: We identified 7 unreported FARS2 variants in patients with HCM. Heart-specific Fars2-deficient mice presented cardiac hypertrophy, left ventricular dilation, progressive heart failure accompanied by myocardial and mitochondrial dysfunction, and a short life span. Heterozygous cardiac-specific Fars2R415L mice displayed a tendency to cardiac hypertrophy at age 4 weeks, accompanied by myocardial dysfunction. In addition, fars2-knockdown zebrafish presented pericardial edema and heart failure. FARS2 deficiency impaired mitochondrial homeostasis by directly blocking the aminoacylation of mt-tRNAPhe and inhibiting the synthesis of mitochondrial proteins, ultimately contributing to an imbalanced mitochondrial quality control system by accelerating mitochondrial hyperfragmentation and disrupting mitochondrion-related autophagy. Interfering with the mitochondrial quality control system using adeno-associated virus 9 or specific inhibitors mitigated the cardiac and mitochondrial dysfunction triggered by FARS2 deficiency by restoring mitochondrial homeostasis. CONCLUSIONS: Our findings unveil the previously unrecognized role of FARS2 in heart and mitochondrial homeostasis. This study may provide new insights into the molecular diagnosis and prevention of heritable cardiomyopathy as well as therapeutic options for FARS2-associated cardiomyopathy.

KbhbXG: A Machine learning architecture based on XGBoost for prediction of lysine ß-Hydroxybutyrylation (Kbhb) modification sites.

Lysine ß-hydroxybutyrylation is an important post-translational modification (PTM) involved in various physiological and biological processes. In this research, we introduce a novel predictor KbhbXG, which utilizes XGBoost to identify ß-hydroxybutyrylation modification sites based on protein sequence information. The traditional experimental methods employed for the identification of ß-hydroxybutyrylated sites using proteomic techniques are both costly and time-consuming. Thus, the development of computational methods and predictors can play a crucial role in facilitating the rapid identification of ß-hydroxybutyrylation sites. Our proposed KbhbXG model first utilizes machine learning algorithm XGBoost to predict ß-hydroxybutyrylation modification sites. On the independent test set, KbhbXG achieves an accuracy of 0.7457, specificity of 0.7771, and an impressive area under the curve (AUC) score of 0.8172. The high AUC score achieved by our method demonstrates its potential for effectively identifying novel ß-hydroxybutyrylation sites, thereby facilitating further research and exploration of the ß-hydroxybutyrylation process. Also, functional analyses have revealed that different organisms preferentially engage in distinct biological processes and pathways, which can provide valuable insights for understanding the mechanism of ß-hydroxybutyrylation and guide experimental verification. To promote transparency and reproducibility, we have made both the codes and dataset of KbhbXG publicly available. Researchers interested in utilizing our proposed model can access these resources at https://github.com/Lab-Xu/KbhbXG.

Synthesis of Multisubstituted 1,2,3-Triazoles: Regioselective Formation and Reaction Mechanism.

A synthetically useful approach to functionalized triazoles is described via the reaction of ß-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

Differential pressure sensors based on transfer-free piezoresistive layered PdSe2thin films.

Piezoresistive layered two-dimensional (2D) crystals offer intriguing promise as pressure sensors for microelectromechanical systems (MEMS) due to their remarkable strain-induced conductivity modulation. However, integration of the conventional chemical vapor deposition grown 2D thin films onto a micromachined silicon platform requires a complex transfer process, which degrades their strain-sensing performance. In this study, we present a differential pressure sensor built on a transfer-free piezoresistive PdSe2polycrystalline film deposited on a SiNxmembrane by plasma-enhanced selenization of a metal film at a temperature as low as 200 °C. Based on the resistance change and finite element strain analysis of the film under membrane deflection, we show that a 7.9 nm thick PdSe2film has a gauge factor (GF) of -43.3, which is ten times larger than that of polycrystalline silicon. The large GF enables the development of a diaphragm pressure sensor with a high sensitivity of 3.9 × 10-4kPa-1within the differential pressure range of 0-60 kPa. In addition, the sensor with a Wheatstone bridge circuit achieves a high voltage sensitivity of 1.04 mV·kPa-1, a rapid response time of less than 97 ms, and small output voltage variation of 8.1 mV in the temperature range of 25 °C to 55 °C. This transfer-free and low-temperature grown PdSe2piezoresistive thin film is promising for MEMS transducer devices.

Association between Hypertrophic Cardiomyopathy and Variations in Sarcomere Gene and Calcium Channel Gene in Adults.

INTRODUCTION: Calcium channel gene variations have been reported to be associated with hypertrophic cardiomyopathy (HCM) in family, but the relationship between calcium channel gene variations and HCM remains undefined in the population. METHODS: A total of 719 HCM unrelated patients were initially enrolled. Finally, 371 patients were identified based on inclusion and exclusion criteria, including 145 patients with gene negative, 28 patients with a single rare calcium channel gene variation (calcium gene variation), 162 patients with a single pathogenic/likely pathogenic sarcomere gene variation (sarcomere gene variation) and 36 patients with a single pathogenic/likely pathogenic sarcomere gene variation and a single rare calcium channel gene variation (double gene variations). Then the demographic, electrocardiographic, echocardiographic, and follow-up data were collected. RESULTS: Patients with double gene variations were at an earlier age and had more percent of family history of HCM, and had thicker walls, higher left ventricular outflow tract pressure gradient, more pathological Q waves, and more bundle branch blocks as compared with those with single sarcomere gene variation. During the follow-up period, patients with double gene variations had more primary endpoints than the other three groups (p = 0.0013). Multivariate analysis showed that double gene variations were the independent predictor of primary endpoint events in patients (HR: 4.82, 95% CI: 1.77-13.2; p = 0.002). CONCLUSION: We found that patients with double gene variations had more severe HCM phenotype and prognosis. The pathogenesis effects of sarcomere gene variation and calcium channel gene variation may be cumulative in HCM populations.

Predictive value of estimated plasma volume for postoperative hypotension in percutaneous intramyocardial septal radiofrequency ablation treating for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Estimated plasma volume status (ePVS) estimated by the Duarte formula is associated with clinical outcomes in patients with heart failure. It remains unclear the predictive value of the ePVS to the postoperative hypotension (POH) in percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) treating hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Data of HOCM patients who underwent PIMSRA were retrospectively collected. Preoperative ePVS was calculated using the Duarte formulas which derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. Patients were labeled with or without POH according to the medical record in the hospital. Univariable and multivariable logistic regression were performed to evaluate the association between ePVS and POH. Using different thresholds derived from quartiles and the best cutoff value of the receiver operating characteristic curve, the diagnostic performance of ePVS was quantified. RESULTS: Among the 405 patients included in this study, 53 (13.1%) patients were observed with symptomatic POH. Median (IQR) of ePVS in overall patients was 3.77 (3.27~4.40) mL/g and in patients with POH were higher than those without POH. The ePVS was associated with POH, with the odds ratio of 1.669 (95% CI 1.299 ~ 2.144) per mL/g. After adjusted by potential confounders, ePVS remained independently associated with POH, with the approximate odds ratio in different models. CONCLUSION: The preoperative ePVS derived from the Duarte formulas was independently associated with postoperative hypotension in HOCM patients who underwent PIMSRA and showed prognostic value to the risk stratification of postoperative management. TRIAL REGISTRATION: NCT06003478 (22/08/2023).

Myocardial contractility characteristics of hypertrophic cardiomyopathy patients with and without sarcomere mutation.

Hypertrophic cardiomyopathy (HCM) patients with sarcomere mutations have an increased risk of heart failure and left ventricular (LV) systolic dysfunction. We hypothesize that sarcomere mutation carriers have abnormal myocardial contractility before LV dysfunction. Therefore, we aimed to associate myocardial contractility with identified sarcomere mutations and predict genotyped HCM patients with sarcomere mutation by three-dimensional speckle tracking imaging (3D-STI). A retrospective analysis of 117 HCM patients identified 32 genotype-positive (G +) and 85 genotype-negative (G-) patients. Genotype-positive patients had higher globe circumferential strain (GCS), globe longitudinal strain (GLS), and globe radial strain (GRS) (p < 0.05), and multivariate logistic regression revealed that these variables were associated with a positive genetic status (p < 0.05). After the propensity matches other possible influencing factors, we developed three models, named Model GCS, Model GLS, and Model GRS, which could identified genotype-positive HCM patients with excellent performance (AUC of 0.855, 0.833, and 0.870 respectively, all p < 0.001). Genotype-positive HCM patients show a higher myocardial hyper-contractility status than patients without sarcomere mutations. When combined with clinical and echocardiographic markers, the 3D-STI parameters can effectively identify the likelihood of genotype-positive HCM.

Feasibility and safety of percutaneous intramyocardial septal cryoablation: A canine model with 6-month follow-up.

Echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is a novel treatment option for hypertrophic obstructive cardiomyopathy (HOCM). The safety and feasibility of using this procedure for cryoablation are unknown. We aimed to investigate the feasibility and safety of echocardiography-guided percutaneous intramyocardial septal cryoablation (PIMSCA) for septal thickness reduction in a canine model. Eight canines underwent PIMSCA, and had electrocardiography, echocardiography(ECG), myocardial contrast echocardiography (MCE), serological and pathological examinations during the preoperative, immediate postoperative, and 6-month follow-up. All eight canines underwent successful cryoablation and continued to be in sinus rhythm during ablation and without malignant arrhythmias. MCE showed that the ablation area had decreased myocardial perfusion after the procedure. Troponin I levels were significantly elevated [0.010 (0.005, 0.297) ng/mL vs. 3.122 (1.152, 7.990) ng/mL, p < 0.05)]. At 6-month follow-up after the procedure, all animals were alive, with thinning of the interventricular septum (7.26 ± 0.52 mm vs. 3.86 ± 0.29 mm, p < 0.05). Echocardiography showed no significant decrease in the left ventricular ejection fractions (LVEF) (54.32 ± 2.93 % vs. 54.70 ± 2.47 %, p > 0.05) or changes by pulse-wave Doppler E/A (1.17 ± 0.43 vs. 1.07 ± 0.43, p > 0.05), E/e' (8.09 ± 1.49 vs. 10.05 ± 2.68, p > 0.05). Pathological findings proved the effectiveness of cryoablation in myocardial tissues. We observed pericardial effusions and premature ventricular complexes (PVCs) associated with the procedure. Our findings provided preliminary evidence of the safety and feasibility of PIMSCA in reducing interventricular septum, which provides a potentially new treatment option for HOCM.

Genetic algorithm-based optical proximity correction for DMD maskless lithography.

We present an optical proximity correction (OPC) method based on a genetic algorithm for reducing the optical proximity effect-induced pattern distortion in digital micromirror device (DMD) maskless lithography. Via this algorithm-assisted grayscale modulation of the initial mask at the pixel level, the exposure pattern can be enhanced significantly. Actual exposure experiments revealed that the rate of matching between the final exposure pattern and the mask pattern can be increased by up to 20%. This method's applicability to complex masks further demonstrates its universality for mask pattern optimization. We believe that our algorithm-assisted OPC could be highly helpful for high-fidelity and efficient DMD maskless lithography for microfabrication.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

Association between triglyceride glucose index and subclinical left ventricular systolic dysfunction in patients with type 2 diabetes.

BACKGROUND: The triglyceride glucose (TyG) index has been considered a new biomarker for the diagnosis of angiocardiopathy and insulin resistance. However, the association of the TyG index with subclinical left ventricular (LV) systolic dysfunction still lacks comprehensive exploration. This study was carried out to examine this relationship in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 150 T2DM patients with preserved LV ejection fraction (LVEF ≥ 50%) from June 2021 to December 2021 were included in this study. The subclinical LV function was evaluated through global longitudinal strain (GLS), with the predefined GLS < 18% as the cutoff for subclinical LV systolic dysfunction. The TyG index calculation was obtained according to ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2), which was then stratified into quartiles (TyG index-Q). RESULTS: Analyses of clinical characteristics in the four TyG indexes-Q (Q1 (TyG index ≤ 8.89) n = 38, Q2 (8.89 < TyG index ≤ 9.44) n = 37, Q3 (9.44 < TyG index ≤ 9.83) n = 38, and Q4 (TyG index > 9.83) n = 37) were conducted. A negative correlation of the TyG index with GLS (r = -0.307, P < 0.001) was revealed according to correlation analysis. After gender and age were adjusted in multimodel logistic regression analysis, the higher TyG index (OR 6.86; 95% CI 2.44 to 19.30; P < 0.001, Q4 vs Q1) showed a significant association with GLS < 18%, which was still maintained after further adjustment for related clinical confounding factors (OR 5.23, 95% CI 1.12 to 24.51, p = 0.036, Q4 vs Q1). Receiver operator characteristic analysis indicated a diagnostic capacity of the TyG index for GLS < 18% (area under curve: 0.678; P < 0.001). CONCLUSIONS: A higher TyG index had a significant association with subclinical LV systolic dysfunction in T2DM patients with preserved ejection fraction, and the TyG index may have the potential to exert predictive value for myocardial damage.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

KOtBu-Mediated Reductive Cyanation of Tertiary Amides for Synthesis of α-Aminonitriles.

A simple, mild, catalyst-free, and efficacious KOtBu-mediated reductive cyanation reaction of tertiary amides under hydrosilylation conditions has been described. A series of α-aminonitriles is obtained in moderate to high yield with good functional group tolerance. The reaction works well with a readily available amide substrate, a cheap and versatile base KOtBu, and a commercially available hydrosilane (EtO)3SiH and is convenient for workup and purification.

Genetic characteristics of human papillomavirus type 16, 18, 52 and 58 in southern China.

Persistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 338 viral genomes of four major HPV types, including HPV 16 (n = 82), 18 (n = 35), 52 (n = 121) and 58 (n = 100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 sublineages associated with potentially high oncogenicity. These findings expanded our knowledge of the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.

Does the environmental inequality matter? A literature review.

The environmental inequality theory reveals that the risk of environmental pollution exposure varies among regions and groups and that particular groups face a higher threat of environmental pollution. In recent years, studies on the environmental inequality issue in developed countries have been increasing, while related literature on developing countries is very scarce. It has been found that some factors, such as race and economic status, have a close relationship with the risk of environmental pollution exposure faced by individuals. For the first time, this paper provides an extensive review of existing theoretical and empirical studies on environmental inequality. We review, in detail, the evolution of the environmental inequality theory, including the definition and measurement of environmental inequality. Further, we provide a systematic refresher on the main performance of environmental inequality, including health, education, labor productivity, and real estate prices. We also identify several causes of environmental inequality, such as ethnic differences, economic status, human capital, and household registration systems. Finally, we discuss prospects for the future research on this issue.

Biosynthesis of vanillin by different microorganisms: a review.

Vanillin is a popular flavoring agent widely used around the world. Vanillin is generated by natural extraction, chemical synthesis, or tissue culture technology, but these production methods no longer meet the increasing worldwide demand for vanillin. Accordingly, a biotechnological approach may provide an effective replacement route to obtaining vanillin. Processes for environmentally friendly production of vanillin in microorganisms from different carbon sources, such as eugenol, isoeugenol, lignin, ferulic acid, sugars, and waste residues, with high productivity and yield have been developed. However, challenges remain for optimizing the vanillin biosynthesis process and further improving production titer and yield. In this review, successful and applicable strategies for increasing vanillin titer and yield in different microorganisms are summarized. Additionally, perspectives for further optimizing the production of vanillin are discussed.

Microbial production of valuable chemicals by modular co-culture strategy.

Nowadays, microbial synthesis has become a common way for producing valuable chemicals. Traditionally, microbial production of valuable chemicals is accomplished by a single strain. For the purpose of increasing the production titer and yield of a recombinant strain, complicated pathways and regulation layers should be fine-tuned, which also brings a heavy metabolic burden to the host. In addition, utilization of various complex and mixed substrates further interferes with the normal growth of the host strain and increases the complexity of strain engineering. As a result, modular co-culture technology, which aims to divide a target complex pathway into separate modules located at different single strains, poses an alternative solution for microbial production. Recently, modular co-culture strategy has been employed for the synthesis of different natural products. Therefore, in this review, various chemicals produced with application of co-cultivation technology are summarized, including co-culture with same species or different species, and regulation of population composition between the co-culture members. In addition, development prospects and challenges of this promising field are also addressed, and possible solution for these issues were also provided.

[Analysis of phenotype and MYH7 gene variant in a family of patients with hypertrophic cardiomyopathy].

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION: The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.