Carrier frequencies, trends, and geographical distribution of hearing loss variants in China: The pooled analysis of 2,161,984 newborns.

The aim of this study is to comprehensively investigate the prevalence and distribution patterns of three common genetic variants associated with hearing loss (HL) in Chinese neonatal population. Methods: Prior to June 30, 2023, an extensive search and screening process was conducted across multiple literature databases. R software was utilized for conducting meta-analyses, cartography, and correlation analyses. Results: Firstly, our study identified a total of 99 studies meeting the inclusion criteria. Notably, provinces such as Qinghai, Tibet, Jilin, and Heilongjiang lack large-scale genetic screening data for neonatal deafness. Secondly, in Chinese newborns, the carrier frequencies of GJB2 variants (c.235delC, c.299_300delAT) were 1.63 % (95 %CI 1.52 %-1.76 %) and 0.33 % (95 %CI 0.30 %-0.37 %); While SLC26A4 variants (c.919-2A > G, c.2168A > G) exhibited carrier rates of 0.95 % (95 %CI 0.86 %-1.04 %) and 0.17 % (95 %CI 0.15 %-0.19 %); Additionally, Mt 12S rRNA m.1555 A > G variant was found at a rate of 0.24 % (95 % CI 0.22 %-0.26 %). Thirdly, the mutation rate of GJB2 c.235delC was higher in the east of the Heihe-Tengchong line, whereas the mutation rate of Mt 12S rRNA m.1555 A > G variant exhibited the opposite pattern. Forthly, no significant correlation exhibited the opposite pattern of GJB2 variants, but there was a notable correlation among SLC26A4 variants. Lastly, strong regional distribution correlations were evident between mutation sites from different genes, particularly between SLC26A4 (c.919-2A > G and c.2168A > G) and GJB c.299_300delAT. Conclusions: The most prevalent deafness genes among Chinese neonates were GJB2 c.235delC variant, followed by SLC26A4 c.919-2A > G variant. These gene mutation rates exhibit significant regional distribution characteristics. Consequently, it is imperative to enhance genetic screening efforts to reduce the incidence of deafness in high-risk areas.

SARS-CoV-2 transmission via maritime cold chains: A statistical analysis of nucleic acid detection results of cold chain food imported from Fuzhou ports.

Numerous epidemic outbreaks related to cold chains have occurred since the coronavirus disease 2019 (COVID-19) outbreak, suggesting the potential danger of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission through cold chain foods (CCFs). By analyzing SARS-CoV-2 RNA contamination of CCFs imported from Fuzhou ports, this study evaluated the contamination and transmission of SARS-CoV-2 RNA via maritime cold chains, with the aim of provide suggestions for CCFs supervision and public health management. The statistical analysis included 131,385 samples. The majority of the CCFs imported into Fuzhou ports was aquatic raw food that originated in Southeast Asia (57.08 %), South America (19.87 %), and South Asia (11.22 %). South Asia had the highest positivity rate of 0.37 %, followed by Southeast Asia (0.21 %) and South America (0.08 %). The positivity rate showed that the outer packaging of CCFs was the most easily contaminated, accounting for 81.33 % of all positive samples. This suggested that CCFs storage and loading processes were the weak links vulnerable to SARS-CoV-2 contamination. The positivity rates in outer packaging, inner packaging, and content of raw food were 0.48 %, 0.08 %, and 0.05 %, respectively, which were obviously higher than those of processed and refined food. This indicated that increasing the mechanization of factories and implementing sensible worker management practices may decrease viral contamination. The monthly positivity rates varied widely from 0 % (March 2021) to 0.40 % (January 2021), with an average of 0.19 %. The positivity rates in outer packaging, inner packaging and content of crustaceans from Southeast Asia were 2.47 %, 0.41 %, and 0.69 %, which were approximately 5-14 times higher than those of fish and cephalopods. Meanwhile, the monthly detection number show that SARS-CoV-2 epidemic prevention strategies affected the trade of imported CCFs.

Evaluation of a novel lyophilized-pellet-based 2019-nCoV nucleic acid detection kit for the diagnosis of COVID-19.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the world and poses a serious threat to human health. In the post-pandemic-era, we must remain vigilant against the co-infection of SARS-CoV-2 and other respiratory viruses. More accurate and convenient detection methods are required for the diagnosis of SARS-CoV-2 due to its prolonged existence. In this study, the application value of a novel lyophilized-pellet-based 2019-nCoV nucleic acid diagnostic kit (PCoV-Kit) was evaluated by comparing it with a conventional liquid diagnostic kit (LCoV-Kit). We assessed the sensitivity, precision, accuracy, specificity, and amplification efficiency of PCoV-Kit and LCoV-Kit using diluted SARS-CoV-2 RNA reference materials. The results showed that both kits had high sensitivity, precision, accuracy, and specificity. A total of 2,033 oropharyngeal swab specimens collected during mass screening in Fuzhou in December 2022 were applied for the consistency analysis of the two reagents. In the detection of clinical oropharyngeal swab specimens, although the positive rate of PCoV-Kit (19.28%) was slightly lower than that of LCoV-Kit (20.86%), statistical analysis demonstrated a high degree of consistency between the test results obtained using both kit (χ2 = 1.57, P>0.05; Kappa coefficient = 0.90, 95%CI: 0.88-0.93). In conclusion, the use of lyophilized PCoV-Kit provides a non-inferior assay for the diagnosis of COVID-19.

Long non-coding RNA DARS-AS1 promotes tumor progression by directly suppressing PACT-mediated cellular stress.

Cancer cells evolve various mechanisms to overcome cellular stresses and maintain progression. Protein kinase R (PKR) and its protein activator (PACT) are the initial responders in monitoring diverse stress signals and lead to inhibition of cell proliferation and cell apoptosis in consequence. However, the regulation of PACT-PKR pathway in cancer cells remains largely unknown. Herein, we identify that the long non-coding RNA (lncRNA) aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) is directly involved in the inhibition of the PACT-PKR pathway and promotes the proliferation of cancer cells. Using large-scale CRISPRi functional screening of 971 cancer-associated lncRNAs, we find that DARS-AS1 is associated with significantly enhanced proliferation of cancer cells. Accordingly, knocking down DARS-AS1 inhibits cell proliferation of multiple cancer cell lines and promotes cancer cell apoptosis in vitro and significantly reduces tumor growth in vivo. Mechanistically, DARS-AS1 directly binds to the activator domain of PACT and prevents PACT-PKR interaction, thereby decreasing PKR activation, eIF2α phosphorylation and inhibiting apoptotic cell death. Clinically, DARS-AS1 is broadly expressed across multiple cancers and the increased expression of this lncRNA indicates poor prognosis. This study elucidates the lncRNA DARS-AS1 directed cancer-specific modulation of the PACT-PKR pathway and provides another target for cancer prognosis and therapeutic treatment.

Spatiotemporal Analysis of Online Purchase of HIV Self-testing Kits in China, 2015-2017: Longitudinal Observational Study.

BACKGROUND: Since the introduction of HIV self-testing by UNAIDS in 2014, the practice has been extensively implemented around the world. HIV self-testing (HIVST) was developed in China around 2015, and the online purchase of HIVST kits through e-commerce platforms has since become the most important delivery method for self-testing, with advantages such as user-friendliness, speed, and better privacy protection. OBJECTIVE: Understanding the spatiotemporal characteristics of online HIVST kit purchasing behavior and identifying potential impacting factors will help promote the HIV self-testing strategy. METHODS: The online retail data of HIVST kits from the 2 largest e-commerce platforms in China from 2015 to 2017 were collected for this study. The Bayesian spatiotemporal hierarchical model was used to investigate the spatiotemporal characteristics of online purchased HIVST kits. Ordinary least squares regression was used to identify potential factors associated with online purchase, including GDP per capita, population density, road density, HIV screening laboratory density, and newly diagnosed HIV/AIDS cases per 100,000 persons. The q statistics calculated by Geodetector were used to determine the interactive effect of every 2 factors on the online purchase. RESULTS: The online purchase of HIVST kits increased rapidly in China from 2015 to 2017, with annual peak sales in May and December. Five economically superior regions in China, Pearl River Delta, Yangtze River Delta, Chengdu and surrounding areas, Beijing and Tianjin areas, and Shandong Peninsula, showed a comparatively higher spatial preference for online purchased HIVST kits. The GDP per capita (P<.001) and the rate of newly diagnosed HIV/AIDS cases per 100,000 persons (P<.001) were identified as 2 factors positively associated with online purchase. Among the factors we investigated in this study, 2 factors associated with online purchase, GDP per capita and the rate of newly diagnosed HIV/AIDS cases per 100,000 persons, also displayed the strongest interactive effect, with a q value of 0.66. CONCLUSIONS: Individuals in better-off areas are more inclined to purchase HIVST kits online. In addition to economic status, the severity of the HIV epidemic is also a factor influencing the online purchase of HIVST kits.

Hydroxyethyl cellulose sensitized SMDMS structure with optical fiber relative humidity and temperature simultaneous measurement sensor.

We have manufactured an intensity modulated optical fiber SMDMS sensor with hydroxyethyl cellulose (HEC) hydrogel coating for simultaneous measurement of RH and temperature. The SMDMS sensor was manufactured by splicing single-mode fiber (SMF), multi-mode fiber (MMF), dispersion compensation fiber (DCF), MMF, and SMF in sequence to form a structure of SMF + MMF + DCF + MMF + SMF (SMDMS). The cladding of MMFs and DCF were corroded by hydrofluoric acid (HF) and coated with HEC hydrogel to excite a strong evanescent field and increase the sensitivity of the SMDMS sensor. The adsorption of water molecules by HEC will cause a change in the effective refractive index of cladding mode, which will eventually change the intensity of the transmission spectrum. The experimental results indicate that the sensitivities are 0.507 dB/%RH and 0.345 dB/°C in the RH range of 30%-80% and temperature range of 10°C-50°C, respectively. At last, a dual-parameter measurement matrix is constructed based on the experimental results to achieve the simultaneous measurement of RH and temperature. The SMDMS sensor has the advantages of high sensitivity and good robustness, and has potential application prospects in daily life and other fields.

Single core-offset Mach-Zehnder interferometer coated with PVA for simultaneous measurement of relative humidity and temperature.

A single core-offset Mach-Zehnder interferometer (MZI) coated with polyvinyl alcohol (PVA) for simultaneous measurement of relative humidity (RH) and temperature is proposed in this paper. The sensing structure is fabricated by splicing dispersion compensating fiber (DCF) and no-core fiber (NCF) and splicing two single-mode fibers (SMF) at both ends, where the core-offset is located at the splicing of SMF and DCF. A part of the cladding of DCF is etched to excite the high-order cladding mode (LP10), and PVA is coated on the etched area. The refractive index of PVA varies due to the adsorption of water molecules. Therefore, when the ambient relative humidity and temperature change, the change of MZI phase difference causes the wavelength of the resonant dip to shift. The experimental results indicate that the proposed sensor has a sensitivity of 0.256 nm/RH% for RH range of 30%-95%, and a sensitivity of 0.153 nm/℃ for temperature range of 20℃-80℃, respectively. The simultaneous measurement of RH and temperature can be achieved by demodulating the sensitivity coefficient matrix. The proposed sensor has the characteristics of good repeatability, high sensitivity, and good stability, which make it potentially applications for the detection of RH and temperature measurement.

High-Throughput Strategies for the Discovery of Anticancer Drugs by Targeting Transcriptional Reprogramming.

Transcriptional reprogramming contributes to the progression and recurrence of cancer. However, the poorly elucidated mechanisms of transcriptional reprogramming in tumors make the development of effective drugs difficult, and gene expression signature is helpful for connecting genetic information and pharmacologic treatment. So far, there are two gene-expression signature-based high-throughput drug discovery approaches: L1000, which measures the mRNA transcript abundance of 978 "landmark" genes, and high-throughput sequencing-based high-throughput screening (HTS2); they are suitable for anticancer drug discovery by targeting transcriptional reprogramming. L1000 uses ligation-mediated amplification and hybridization to Luminex beads and highlights gene expression changes by detecting bead colors and fluorescence intensity of phycoerythrin signal. HTS2 takes advantage of RNA-mediated oligonucleotide annealing, selection, and ligation, high throughput sequencing, to quantify gene expression changes by directly measuring gene sequences. This article summarizes technological principles and applications of L1000 and HTS2, and discusses their advantages and limitations in anticancer drug discovery.

A smartphone-assisted microfluidic chemistry analyzer using image-based colorimetric assays for multi-index monitoring of diabetes and hyperlipidemia.

A smartphone-assisted microfluidic chemistry analyzer using an image-based colorimetric detection method was successfully developed for the simultaneous analysis of three diabetes- and hyperlipidemia-related indexes, glucose (GLU), triglyceride (TG), and total cholesterol (TC). A fan-shaped microfluidic chip was designed and optimized to reliably allocate a premixed serum sample into four reaction chambers by a simple pipetting. The color changes of the peroxidase-H2O2 enzymatic reactions in the chambers were captured and analyzed using a smartphone-controlled analyzer with a LED light source and a CCD camera. The highly quantitative relationships between the analyte concentrations and the color characteristic values of the green channel of the captured images were successfully established, enabling accurate and reproducible detections of GLU, TG, and TC simultaneously at a low cost. The parallel analyses of 111 serum samples using our system and a conventional chemistry analyzer were conducted, yielding an excellent correlation and consistency between these two systems. This study proved the feasibility of performing the multi-index monitoring of diabetes, hyperlipidemia, and other chronic diseases on a point-of-care platform at a high fidelity, but a low cost.

Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection

Background: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. Objective: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. Methods: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. Results: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either ade-fovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. Conclusion: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus. .

Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection.

BACKGROUND: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. OBJECTIVE: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. METHODS: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. RESULTS: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either adefovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. CONCLUSION: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus.

Systematic dielectrophoretic analysis of the Ara-C-induced NB4 cell apoptosis combined with gene expression profiling.

Dielectrophoresis (DEP) can be used to noninvasively measure the dielectric state of the cell, and this data can be used to monitor cell health or apoptosis. In this study, we followed events associated with cytosine arabinoside (Ara-C)-induced apoptosis in NB4 cells using DEP analysis. Our data showed that the membrane capacitance of NB4 cells decreases from 9.42 to 7.63 mF/m(2) in the first 2 hours following treatment with Ara-C, and that this decreased capacitance persists for >12 hours. Additionally, cytoplasmic conductivity decreases from 0.217 to 0.190 S/m within 2 hours of Ara-C treatment; this level is maintained for a short period of time before decreasing. We also investigated these events molecularly at the level of gene expression using microarray analysis and showed that the expression of genes related to membrane capacitance and cytoplasmic conductivity change dramatically as early as 2 hours post-Ara-C treatment, and further demonstrated a temporal relationship between the dielectric properties and key events in apoptosis. This study, integrating physical electrical properties of the cell membrane and cytoplasm with those of conductivity-related gene networks, provides new insights into the molecular mechanisms underlying the initiation of apoptosis, establishing a systematic foundation for DEP application in follow-up drug screening and development of medicines for treating leukemia.

Validation of a mobile phone-assisted microarray decoding platform for signal-enhanced mutation detection.

We have established a mobile phone-assisted microarray decoding platform for signal-enhanced mutation detection. A large amount of single-stranded DNA (ssDNA) was obtained by combining symmetric PCR and magnetic isolation, and ssDNA prepared with magnetic bead as label was further allowed to hybridize against the tag-array for decoding purpose. High sensitivity and specificity was achieved with the detection of genomic DNA. When simultaneously genotyping nine common mutations associated with hereditary hearing loss, the detection limit of 1 ng genomic DNA was achieved. Significantly, a mobile phone was also used to record and decode the genotyping results through a custom-designed imaging adaptor and a dedicated mobile phone software. A total of 51 buccal swabs from patients probably with deafness-related mutations were collected and analyzed. The genotyping results were all confirmed by fluorescence-based laser confocal scanning and direct DNA sequencing. This mobile phone-assisted decoding platform provides an effective but economic mutation detection alternative for the future quicker and sensitive detection of virtually any mutation-related diseases in developing and underdeveloped countries.

Long distance fiber-optic displacement sensor based on fiber collimator.

A simple fiber-optic displacement sensor based on reflective intensity modulated technology is demonstrated using a fiber collimator. The sensing range is over 30 cm, which is over 100 times that of the conventional fiber-optic displacement sensor based on the normal single-mode fiber. The measured data are fitted into linear equation very well and the values of R-square are more than 0.995. The sensitivity of the device achieves 0.426 dB∕cm over the range of 5-30 cm. By applying the relative technique, the errors resulted from the fluctuation of light source and influences of environment are effectively eliminated, and the stability for wide range measurement can be improved. The simplicity of the design, high dynamic range, stability and the ease of the fabrication make it suitable for applications in industries.

Development of a base stacking hybridization-based microarray method for rapid identification of clinical isolates.

A base stacking hybridization-based microarray method was developed for rapid identification of clinical isolates within 2 h. The oligonucleotide probe sequences for species or genus-level identification were targeted against ribosomal RNA. Isolates were lysed and directly hybridized to the microarray-bound capture probes without conventional DNA or RNA isolation and prior polymerase chain reaction amplification. Five bacterial species encountered frequently in the clinical setting, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae, and one genus Enterococcus, could be discriminated by the microarray-based assay. Identification by this method matched biochemical identification for 150 of 152 clinical strains. This base-stacking hybridization microarray offers a simple, fast (