Detection of organic arsenic based on acid-base stable coordination polymer.

Organic arsenic, usually found in animal feed and livestock farm wastewater, is a carcinogenic and life-threatening substance. Hence, for the rapid and sensitive detection of organic arsenic, the development of new fluorescent sensors is quite essential. Here, an acid-base stable coordination polymer (HNU-62) was constructed by the introduction of hydrophobic fluorescence ligand, which can be used as a highly selective sensor for the detection of roxarsone (ROX) in water. The limit of detection (LOD) of HNU-62 for ROX was 4.5 × 10-6 M. Furthermore, HNU-62 also exhibits good anti-interference and recyclability, which can be used in detecting ROX in real samples of pig feed. This work provides an alternative approach for the construction of water-stable coordination polymer-based fluorescence sensors.

Xylenol orange-modified CdTe quantum dots as a fluorescent/colorimetric dual-modal probe for anthrax biomarker based on competitive coordination.

Bacillus anthracis spores can make humans infected with vicious anthrax, so it is significant to detect their biomarker 2,6-pyridinedicarboxylic acid (DPA). The development of dual-modal methods for DPA detection that are more flexible in practical applications remains a challenge. Herein, colorimetric xylenol orange (XO) was modified on fluorescent CdTe quantum dots (QDs) for dual-modal detection of DPA through competitive coordination. After the binding of XO on CdTe QDs via coordination with Cd2+, CdTe QDs displayed quenched red fluorescence and the bound XO was presented as red color. The competitive coordination of DPA with Cd2+ made XO released from CdTe QDs, causing the enhanced red fluorescence of CdTe QDs and the yellow color of free XO. On this basis, DPA was rapidly (1 min) quantified through fluorescent and colorimetric modes within the ranges of 0.1-5 µM and 0.5-40 µM, respectively. The detection limits for DPA were calculated as low as 42 nM and 240 nM, respectively assigned to fluorescent and colorimetric modes. The level of urinary DPA was further measured. Satisfactory relative standard deviations (fluorescent mode: 0.1%-10.2%, colorimetric mode: 0.8%-1.8%) and spiked recoveries (fluorescent mode: 100.0%-115.0%, colorimetric mode: 86.0%-96.6%) were obtained.

Bifunctional ratiometric fluorescent probe for sensing anthrax spore biomarker and tetracycline at different excitation channels.

Multifunctional fluorescent probes have received increasing attention for the sake of atom economy and high-density integration. Herein, CdTe quantum dots (QDs) modified with Eu3+ were synthesized as the bifunctional ratiometric fluorescent probe for sensing two hazardous substances tetracycline (TC) and anthrax spore biomarker 2,6-dipicolinic acid (DPA) at different excitation channels, based on the discrepant excitation wavelengths of Eu3+ and the fluorescence quenching of CdTe QDs after interaction with them. Both DPA and TC enhanced the red emission of Eu3+ via antenna effect but caused the green emission of CdTe QDs to quench. Interestingly, the excitation wavelengths of Eu3+ after coordinating with DPA and TC were 275 and 386 nm, respectively. On this basis, CdTe QDs-Eu3+ achieved the bifunctional ratiometric detection of DPA (λex = 275 nm) and TC (λex = 386 nm) with different excitation channels. Both DPA and TC were selectively detected by CdTe QDs-Eu3+ with rapid response (DPA-1 min, TC-1 min) and high sensitivity (DPA-LOD 0.3 µM, TC-LOD 2.2 nM). CdTe QDs-Eu3+ were applied to analyzing DPA and TC in food, biological and environmental samples. Satisfactory spiked recoveries (80.0-119.0 %) and relative standard deviations (0.5-8.4 %) were obtained for measuring DPA and TC in these samples.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

Enzyme-free fluorescence determination of uric acid by combining CdTe quantum dots with metal-organic framework for signal amplification.

The composite of CdTe quantum dots (QDs) with ZIF-8 was elaborately designed and synthesized as an enzyme-free fluorescent probe for the sensitive determination of uric acid (UA), based on the fluorescence detection property of CdTe QDs and the signal amplification function of ZIF-8. The structure and feature of the composite were characterized with transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, and fluorescence spectrometry. With adding UA to the composite, the emission of CdTe QDs reduced due to the inner filter and dynamic quenching effects of UA, and the adsorption ability of ZIF-8 toward UA promoted the response signal of CdTe QDs. On this basis, UA was quantified by the composite in the concentration range 0.05 to 10 µM with excitation/emission wavelength at 287/615 nm, and the detection limit of the composite toward UA was 32 nM. The reproducibility of the composite for determining UA was further evaluated, and the relative standard deviations were below 10.2%. The composite also exhibited the merits of enzyme-free analysis such as low testing cost, short analysis time (1 min), and loose pH condition (application in whole physiological pH range, 5.0 - 8.0). The composite was applied to the determination of UA in human urine with recoveries of spiked samples in the range 99 to 113%.

Virtual reality training improves accommodative facility and accommodative range.

AIM: To evaluate the effects of virtual reality (VR) training on different parameters of vision. METHODS: Sixty individuals ranged 18-60 years old with asthenopia were randomly divided into short-term (n=40) and long-term (n=20) treatment groups. They were given a specially designed VR training device only once for 15min or 3-4 times a day for 15min each time for 1mo. The visual acuity, spherical equivalent, accommodative range, accommodative facility, pupil size, and visual fatigue were evaluated before (control) and after VR training. RESULTS: The visual acuity, accommodative range, and accommodative facility increased in subjects of the short-term treatment group, whereas their pupil size contracted significantly. No significant changes in spherical equivalent and visual fatigue were observed. The changes in distant vision and corrected visual acuity were positively correlated with those in pupil size, but not with spherical equivalent. The accommodative range and accommodative facility improved significantly in subjects of the long-term treatment group. No significant changes in visual acuity, spherical equivalent, pupil size, and visual fatigue were noted. CONCLUSION: VR training can improve the accommodative range and accommodative facility of human eyes. Although short-term VR training can transiently improve vision, which probably due to bright light adaptation, there is no evidence that it can improve myopia.

Recent advances in yeast genome evolution with stress tolerance for green biological manufacturing.

Green biological manufacturing is a revolutionary industrial model utilizing yeast as a significant microbial cell factory to produce biofuels and other biochemicals. However, biotransformation efficiency is often limited owing to several stress factors resulting from environmental changes or metabolic imbalance, leading to the slow growth of cells, compromised yield, and enhanced energy consumption. These factors make biological manufacturing competitively less economical. In this regard, minimizing the stress impact on microbial cell factories and strong robust performance have been an interesting area of interest in the last few decades. In this review, we focused on revealing the stress factors and their associated mechanisms for yeast in biological manufacturing. To improve yeast tolerance, rational and irrational strategies were introduced, and the molecular basis of genome evolution in yeast was also summarized. Furthermore, strategies of genome-directed evolution such as homology directed repair and nonhomologous end-joining, and the synthetic chromosome recombination and modification by LoxP-mediated evolution and their association with stress tolerance was highlighted. We hope that genome evolution provides new insights for solving the limitations of the natural phenotypes of microorganisms in industrial fermentation for the production of valuable compounds.

CdTe QDs@ZIF-8 composite-based recyclable ratiometric fluorescent sensor for rapid and sensitive detection of chlortetracycline.

The residue problem in animal food products caused by the abuse of chlortetracycline (CTC) is one of the food safety issues that have attracted much attention. Herein, a composite was generated by embedding CdTe quantum dots (QDs) into ZIF-8 for ratiometric fluorescent analysis of CTC. With adding CTC, the green luminescence of CTC appeared under the sensitization effect of Zn2+ in ZIF-8, but the red luminescence of CdTe QDs was reduced by the inner filtration effect of CTC. On this basis, CTC was detected by the composite with a short response time of 1 min, and the limit of detection was calculated to be 37 nM that was 17 times lower than the maximum residue limit of CTC in animal food products (626 nM). Excellent recyclability of the composite was also observed, and CTC was consecutively measured at least six times. The composite was used to determine CTC in basa fish and pure milk with satisfactory recoveries (91.0-110.0%). Portable test strips were further manufactured and the visual determination of CTC was obtained. These results convictively demonstrate that CdTe QDs@ZIF-8 composite as a recyclable ratiometric fluorescent sensor achieves the rapid and sensitive measurement of CTC residue in animal food products.

A ratiometric fluorescence-scattering sensor for rapid, sensitive and selective detection of doxycycline in animal foodstuffs.

The residue problem of tetracycline antibiotics, especially doxycycline (DC), in animal foodstuffs has attracted much attention. This paper reported ZIF-8 and bovine serum albumin (BSA) as a ratiometric fluorescence-scattering sensor for DC. The mechanism relied on the disassembly of ZIF-8 caused by DC, bringing weakened second-order scattering, and the double fluorescence amplification of DC under ZIF-8 with BSA, inducing enhanced fluorescence. The response of the sensor was completed within 1 min, and the detection limit for DC (3.4 nM) was 1-2 orders of magnitude lower than the reported ones. The distinguishment of DC from other tetracycline antibiotics was also achieved by the sensor. The sensor was applied to detecting DC in animal foodstuffs with satisfactory recoveries (80.0-104.0%). Hence, this work develops a rapid, sensitive and selective ratiometric sensor to monitor the DC residue in animal foodstuffs, also opens the window to construct ratiometric DC sensors with the fluorescence-scattering strategy.

Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.

Identification and characterization of two novel melanocortin-3 receptor mutations in Chinese obese individuals.

The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), known as neural melanocortin receptors, have been implicated to be critical components of the hypothalamic leptin-melanocortin pathway and related to obesity pathogenesis. In contrast to extensive evidence from physiologic, biological, genetic studies demonstrating that MC4R is a critical regulator in obesity, whether MC3R mutation causes obesity is still controversial. In the present study, we screened for coding variants in the MC3R gene of 176 obese individuals (mean BMI 34.84 ± 0.19 kg/m2) and 170 lean controls (mean BMI 20.70 ± 0.08 kg/m2) to assess the prevalence of MC3R mutations in a Chinese cohort. Two novel mutations, A33D (c.C98 > A) and A259T (c.G775 > A), were identified in two subjects with morbid obesity, respectively. A259T was also identified in the carrier's sibling. In vitro functional studies showed that A33D was defective in the cAMP signaling pathway, whereas A259T MC3R had defective maximal binding and cAMP generation in response to NDP- and α-MSH, likely due to decreased cell surface expression. In addition, we showed that A33D and A259T were biased receptors and defect in constitutive activation of ERK1/2 signaling through MC3R might be a cause for morbid obesity. Our sequencing and co-segregation studies combined with comprehensive functional analysis demonstrated that A259T might be predisposing to obesity. Further investigations in larger cohorts will be needed in order to define this association and the specific phenotypic characteristics resulting from these mutations.

Predictive diagnostic value of serum 25-hydroxyvitamin D3 in eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.

Outcomes of 4 surgical adjuvants used for internal limiting membrane peeling in macular hole surgery: a systematic review and network Meta-analysis.

AIM: To compare the outcomes of four adjuvants used for internal limiting membrane (ILM) peeling in macular hole surgery, including indocyanine green (ICG), brilliant blue G (BBG), triamcinolone (TA) and trypan blue (TB), through systematic review and random-effects Bayesian network Meta-analysis. METHODS: PubMed, Cochrane library databases and Web of Science were searched until August 2018 for clinical trials comparing the above four adjuvants. ORs for postoperative best corrected visual acuity (BCVA) improvement and primary macular hole closure rates were compared between the different adjuvants. RESULTS: Twenty-seven eligible articles were included. For postoperative BCVA improvement, results of BBG-assisted peeling were significantly more favorable than those of ICG (WMD 0.08, 95% credible interval 0.01-0.16) and TA ranked highest. No significant differences were found between any other two groups in postoperative BCVA improvement. For postoperative primary macular hole closure rates, BBG ranked highest. However, no significant differences were shown between any two groups. CONCLUSION: TA and BBG are the optimum adjuvants for achieving postoperative BCVA improvement macular hole surgery with adjuvant-assisted ILM peeling. Among all adjuvants, the use of BBG is associated with the highest postoperative macular hole closure rate.

Gastrin, Cholecystokinin, Signaling, and Biological Activities in Cellular Processes.

The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive in vitro and in vivo studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.

Comparison of epidemiological and clinical characteristics of COVID-19 patients with and without Wuhan exposure history in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

BACKGROUND@#A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure.@*METHODS@#We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan.@*RESULTS@#Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups.@*CONCLUSIONS@#From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.

Melanocortin Regulation of Inflammation.

Adrenocorticotropic hormone (ACTH), and α-, ß-, and γ-melanocyte-stimulating hormones (α-, ß-, γ-MSH), collectively known as melanocortins, together with their receptors (melanocortin receptors), are components of an ancient modulatory system. The clinical use of ACTH in the treatment of rheumatoid arthritis started in 1949, originally thought that the anti-inflammatory action was through hypothalamus-pituitary-adrenal axis and glucocorticoid-dependent. Subsequent decades have witnessed extensive attempts in unraveling the physiology and pharmacology of the melanocortin system. It is now known that ACTH, together with α-, ß-, and γ-MSHs, also possess glucocorticoid-independent anti-inflammatory and immunomodulatory effects by activating the melanocortin receptors expressed in the brain or peripheral immune cells. This review will briefly introduce the melanocortin system and highlight the action of melanocortins in the regulation of immune functions from in vitro, in vivo, preclinical, and clinical studies. The potential therapeutic use of melanocortins are also summarized.

Effects of glyphosate on soybean metabolism in strains bred for glyphosate-resistance.

To produce high quality, glyphosate-resistant soybeans, we crossed Jinda 73 and glyphosate-resistant RR1 (Roundup Ready First Generation) (RR1) resulting in 34 hybrid strains. To determine the effects of glyphosate on soybean metabolism, we grew the two parents upto the seedling stage, and measured chlorophyll, soluble sugar, malondialdehyde (MDA), relative conductivity and proline. Then, we treated the plants with glyphosate and measured the same factors again. Results showed that the chlorophyll content of Jinda 73 and RR1 decreased after spraying glyphosate. Glyphosate increased the level of soluble sugar, MDA, relative conductivity and proline in Jinda 73, but had no significant effect on RR1. We determined glyphosate resistance of the parents and the 34 hybrid, offspring strains by documenting the growth response in the field after treatment with glyphosate. Results showed that 29 hybrid, offspring strains have complete glyphosate resistance. Polymerase chain reaction (PCR) shows that the strains which have complete resistance to glyphosate have imported the CP4 5-enolpyhruvylshikimate-3- phosphate synthase (CP4 EPSPS) gene successfully. We selected three high quality, glyphosate-resistant strains (F7-3, F7-16 and F7-21), which had higher protein and oil levels as compared with Jinda 73.

Therapeutic strategies for diseases caused by loss-of-function mutations in G protein-coupled receptors.

As one of the largest families of cell membrane proteins, G protein-coupled receptors (GPCRs) are involved in regulating almost all physiological processes by transducing extracellular signals into the cytoplasm. Since the first discovery of naturally occurring mutations in Rhodopsin gene in 1990, hundreds of loss-of-function mutations in multiple GPCRs have been identified to be pathogenic for more than 30 diverse human diseases, making these defective receptors important drug targets for personalized medicine. In this review, we aim to elucidate the etiologies of five common inherited diseases caused by six of the most extensively studied GPCRs. The molecular basis and classification of inactivating mutations in GPCRs are also reviewed. The available therapeutic approaches directed against different classes of mutants, especially pharmacological chaperones targeting intracellularly retained mutants, reported during the past two decades, are systematically summarized.

Regulation of prostate cancer by hormone-responsive G protein-coupled receptors.

Regulation of prostate cancer by androgen and androgen receptor (AR), and blockade of AR signaling by AR antagonists and steroidogenic enzyme inhibitors have been extensively studied. G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate almost all physiological processes. Nearly 40% of FDA-approved drugs in the market target GPCRs. A variety of GPCRs that mediate reproductive function have been demonstrated to be involved in the regulation of prostate cancer. These GPCRs include gonadotropin-releasing hormone receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, relaxin receptor, ghrelin receptor, and kisspeptin receptor. We highlight here GPCR regulation of prostate cancer by these GPCRs. Further therapeutic approaches targeting these GPCRs for the treatment of prostate cancer are summarized.

A Meta-analysis of the association between different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy and visual prognosis.

AIM: To analyze the influences of different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy (LHON) on visual prognosis. METHODS: After a systematic literature search, all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included. All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS: Ten independent studies were included finally. A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778A versus T14484C [odds ratio (OR)=0.10, 95% confidence interval (CI)=0.05-0.17, P<0.001], G11778A versus G3460A (OR=0.18, 95%CI=0.09-0.37, P<0.001) and T14484C versus G3460A (OR=2.45, 95%CI=1.10-5.48, P<0.05). In addition, obtained by pairwise comparison, the vision during onset, age of onset and sex ratio of these three kinds of patients, have no statistical significance (P>0.05). CONCLUSION: From pairwise comparison, we conclude that these three different genotypes of LHON are related to patients' visual prognosis. The T14484C patients might have a best prognostic vision, G3460A second, and G11778A worst. And there is little relation between the three different genotypes and patients' vision, age of onset and sex ratio.