Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. METHODS: Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. RESULTS: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). CONCLUSION: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment.

Cas13a-based multiplex RNA targeting for potato virus Y.

MAIN CONCLUSION: The Cas13a-based multiplex RNA targeting system can be engineered to confer resistance to RNA viruses, whereas the number and expression levels of gRNAs have no significant effect on viral interference. The CRISPR-Cas systems provide adaptive immunity to bacterial and archaeal species against invading phages and foreign plasmids. The class 2 type VI CRISPR/Cas effector Cas13a has been harnessed to confer the protection against RNA viruses in diverse eukaryotic species. However, whether the number and expression levels of guide RNAs (gRNAs) have effects on the efficiency of RNA virus inhibition is unknown. Here, we repurpose CRISPR/Cas13a in combination with an endogenous tRNA-processing system (polycistronic tRNA-gRNA) to target four genes of potato virus Y (PVY) with varying expression levels. We expressed Cas13a and four different gRNAs in potato lines, and the transgenic plants expressing multiple gRNAs displayed similar suppression of PVY accumulation and reduced disease symptoms as those expressing a single gRNA. Moreover, PTG/Cas13a-transformed plants with different expression levels of multiple gRNAs displayed similar resistance to PVY strains. Collectively, this study suggests that the Cas13a-based multiplex RNA targeting system can be utilized to engineer resistance to RNA viruses in plants, whereas the number and expression levels of gRNAs have no significant effect on CRISPR/Cas13a-mediated viral interference in plants.

A retrospective cohort study on the treatment outcomes and genotyping of isoniazid-resistant tuberculosis patients in Eastern China.

OBJECTIVES: Isoniazid resistance might be overlooked because of the priority of detection of rifampicin-resistant tuberculosis. It was urgent to reveal the current situation of isoniazid-resistant tuberculosis (HR-TB), including unfavorable outcomes and bacterial factors. METHODS: A retrospective cohort study was undertaken including 120 patients with HR-TB and 193 patients with drug-sensitive tuberculosis (DS-TB). 24-loci MIRU-VNTR and Spoligotyping were adopted for genotyping. RESULTS: We found 106 cases (88.3%) of HR-TB and 165 cases (85.5%) of DS-TB were treated with the first-line drugs. Meanwhile, 12 (10.0%) patients of the HR-TB group and 7 (3.63%) patients of the DS-TB group involved adverse treatment outcomes (χ2 = 5.271, P = 0.028). Seventy-eight DNA from HR Mycobacterium tuberculosis and 114 DNA from DS M. tuberculosis were available for MIRU-VNTR and Spoligotyping. The clustering rate was 17.9% (14/78) for HR-TB and 16.7% (19/114) for DS-TB, and reached no significant difference (χ2 = 0.05, P = 0.8171). The Beijing family strains accounted for 83.7% (65/78) of HR-TB and 80.0% (91/114) of DS-TB (χ2 = 0.37, P = 0.5407). The adverse treatment outcomes for HR-TB all occurred in patients infected with Beijing family strains (13.8%), but no difference was found between Beijing and non-Beijing genotypes (P = 0.342). CONCLUSION: Adverse outcomes were significantly more frequent in patients with HR-TB than in those with DS-TB, and most of the patients with HR-TB were receiving a standard first-line regimen. Although the clustering rate and Beijing genotype distribution amongst HR-TB and DS-TB showed no significant difference, the Beijing genotype was the dominant genotype and its proportion was slightly higher amongst HR-TB than amongst DS-TB.

The Association Between Dietary Inflammatory Index and Cognitive Performance in Older Adults Aged 60 Years and Older.

Background: Neuroinflammation has been linked to the development of cognitive performance. Epidemiological evidence on dietary inflammatory potential and cognitive performance is scarce. We evaluated the association between dietary inflammatory index (DII) and cognitive performance in older adults. Methods: This study included adults aged 60 years or older from the 2011-2014 National Health and Nutrition Examination Survey. The DII scores were calculated based on 27 nutritional parameters. Cognitive performance was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST, n = 2,780), the Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL, n = 2,859) and Delayed Recall (CERAD-DR, n = 2,857), and the Animal Fluency (AF, n = 2,844) tests. Restricted cubic splines and logistic regression were adopted to assess the associations. Results: Comparing the highest to lowest tertile of DII scores, the odds ratio (95% CI) of lower cognitive functioning was 1.97 (1.08-3.58) [P-trend = 0.02, per 1 unit increment: 1.17 (1.01-1.38)] on DSST, 1.24 (0.87-1.76) [P-trend = 0.24, per 1 unit increment: 1.09 (0.96-1.23)] on CERAD-WL, 0.93 (0.57-1.51) [P-trend = 0.74, per 1 unit increment: 1.02 (0.87-1.20)] on CERAD-DR, and 1.76 (1.30-2.37) [P-trend < 0.01, per 1 unit increment: 1.17 (1.05-1.29)] on AF. The above-mentioned associations were observed in both men and women. In non-linear dose-response analysis, the association between DII and lower cognitive functioning was not significant at lower DII scores up to 3.0, after which the association was significant and the curve rose steeply. Conclusion: Higher DII is associated with lower scores on DSST and AF tests in older adults.

Serum Copper and Zinc Concentrations and Cognitive Impairment in Older Adults Aged 60 Years and Older.

Epidemiological evidence on serum zinc and copper and cognitive impairment in older adults are not consistent. Results on serum zinc and copper and cognitive impairment in older adults from the National Health and Nutrition Examination Survey (NHANES) have not been reported. Data on serum zinc and copper and cognitive impairment from individuals ≥ 60 years of age were obtained from the 2011-2014 NHANES. Serum zinc and copper concentrations were determined with inductively coupled plasma dynamic reaction cell mass spectrometry. Cognitive impairment was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST), the Animal Fluency (AF), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR), and the Word Learning (CERAD-WL) tests. Compared with the lowest tertile of serum copper, the multivariate-adjusted odds ratios of scoring low on the AF were 0.86 (0.44-1.68) in tertile 2 and 0.46 (0.25-0.82) in tertile 3, and the inverse association was also found in women. No association was found between serum copper and the DSST, CERAD-DR, and CRAD-WL, respectively. Compared with the lowest tertile of serum zinc, the multivariate-adjusted odds ratios of scoring low on the DSST were 0.83 (0.37-1.90) in tertile 2 and 0.42 (0.22-0.80) in tertile 3, and the inverse association was also found in men. No association was found between serum zinc and the AF, CERAD-DR, and CRAD-WL, respectively. In conclusion, serum copper and zinc were associated with certain cognitive performance tests among older adults, and the causality deserves to be confirmed further.

Deflection estimation of industrial robots with flexible joints.

The application of industrial robots in manufacturing industries has received considerable concerns due to the high flexibility, multifunctionality, and cost-efficiency. It is well known that the robot positioning accuracy is susceptible to the load and motion of robots owing to the insufficient stiffness of robots. Therefore, the machining accuracy improvement has been a research focus in the robotic manufacturing industries in the last decade. To overcome the measurement difficulty of the joint torque and position as well as the complex dynamic coupling between rotors and links, two forward dynamics algorithms for the robot deflection estimation are proposed in this paper. The robot kinematics and dynamics algorithms considering the dynamic coupling between rotors and links are developed based on Lie theory. The forward dynamics equations of robots are solved via the proposed algorithms: the implicit numerical integration algorithm and numerical iterative estimation algorithm. When only the motor position is available, the implicit numerical integration algorithm is employed to solve the forward dynamics equations to estimate the joint torque and position. At the same time, when both the motor position and torque are available, the forward dynamics equations can be reorganized as algebraic equations and solved by the numerical iterative estimation algorithm. Simulations of a 6-DOF serial robot are performed to verify the accuracy of the proposed algorithms.

Association between serum iron concentrations and cognitive impairment in older adults aged 60 years and older: A dose-response analysis of National Health and Nutrition Examination Survey.

Epidemiological evidence on peripheral iron and cognitive impairment in older adults is sparse and limited. Results on serum iron and cognitive impairment in older adults from the National Health and Nutrition Examination Survey have not been reported. Data on serum iron and cognitive impairment from individuals ≥ 60 years of age were obtained from the 2011-2014 NHANES (N = 3,131). Serum iron concentrations were determined with DcX800 method. Cognitive impairment was assessed with four cognitive tests: the Digit Symbol Substitution Test (DSST), the Animal Fluency (AF), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning (CERAD-WL) tests. Logistic regression and restricted cubic splines were adopted to explore the dose-response relationship between serum iron concentrations and cognitive impairment. Comparing the highest to lowest tertile of serum iron concentrations, the multivariate-adjusted odds ratios of scoring low on the DSST were 0.70 (0.49-1.00), 0.88 (0.65-1.20) for CERAD-WL, 0.65 (0.48-0.88) for CERAD-DR, and 0.78 (0.53-1.15) for AF. Stratified analyses by sex showed that the above-mentioned associations were mainly found in men; however, the interaction with sex was not significant. Dose-response analysis showed that relationships between serum iron and cognitive impairment evaluated by DSST and CERAD-DR were linear, respectively.

Formaldehyde Exposure in Indoor Air From Public Places and Its Associated Health Risks in Kunshan City, China.

This study assessed the noncarcinogenic and carcinogenic health risks associated with formaldehyde exposure for employees working in 4 categories of public places in Kunshan City in China. A total of 564 different public places, which can be divided into 4 categories (hotel and social interaction places, bathing and beauty places, cultural and entertainment places, and shopping places), and 2716 indoor air samples in those places were measured from January 1, 2010, to December 31, 2015. The average concentration of formaldehyde was 0.57 mg/m3, which is 5.7 times the acceptable concentration level (0.1 mg/m3). The noncarcinogenic risk assessment index for the 4 categories of places tested was above 1. The carcinogenic risk of formaldehyde for employees of the 4 categories of public places was 4.70 × 10-5 to 1.57 × 10-4, which was greater than the acceptable carcinogenic risk probability (1 × 10-6) from the US Environmental Protection Agency. The highest carcinogenic risk occurred in bathing and beauty places, and male employee carcinogenic risk was greater than that of females. Occupational formaldehyde exposure has serious noncarcinogenic and carcinogenic health risks for employees, and further research is needed to improve indoor air quality in the workplace environment.

Bifunctional Hybrid a-SiO x(Mo) Layer for Hole-Selective and Interface Passivation of Highly Efficient MoO x/a-SiO x(Mo)/n-Si Heterojunction Photovoltaic Device.

The promising n-Si-based solar cell is constructed for the purpose of realizing hole- and electron-selective passivating contact, using a textured front indium tin oxide/MoO x structure and a planar rear a-SiO x/poly(Si(n+)) structure severally. The simple MoO x/n-Si heterojunction device obtains an efficiency of 16.7%. It is found that the accompanying ternary hybrid SiO x(Mo) interlayer (3.5-4.0 nm) is formed at the MoO x/n-Si boundary zone without preoxidation and is of amorphous structure, which is determined by a high-resolution transmission electron microscope with energy-dispersive X-ray spectroscopy mapping. The creation of lower-oxidation states in MoO x film indicates that the gradient distribution of SiO x with Mo element occurs within the interlayer, acting as a passivation of silicon substrate, which is revealed by X-ray photoelectron spectroscopy with depth etching. Specifically, calculations by density functional theory manifest that there are two half-filled levels (localized states) and three unoccupied levels (extended states) relating to Mo component in the ternary hybrid a-SiO x(Mo) interlayer, which play the roles of defect-assisted tunneling and direct tunneling for photogenerated holes, respectively. The transport process of photogenerated holes in the MoO x/n-Si heterojunction device is well-described by the tunnel-recombination model. Meanwhile, the a-SiO x/poly(Si(n+)) has been assembled on the rear of the device for direct tunneling of photoinduced electrons and blocking photoinduced holes.

Cold deep subduction recorded by remnants of a Paleoproterozoic carbonated slab.

The absence of low-thermal gradients in old metamorphic rocks (<350 °C GPa-1) has been used to argue for a fundamental change in the style of plate tectonics during the Neoproterozoic Era. Here, we report data from an eclogite xenolith in Paleoproterozoic carbonatite in the North China craton that argues for cold subduction as early as 1.8 Ga. The carbonatite has a sediment-derived C isotope signature and enriched initial Sr-Nd isotope composition, indicative of ocean-crust components in the source. The eclogite records peak metamorphic pressures of 2.5-2.8 GPa at 650-670 °C, indicating a cold thermal gradient, 250(±15) °C GPa-1. Our data, combined with old low-temperature events in the West African and North American cratons, reveal a global pattern that modern-style subduction may have been established during the Paleoproterozoic Era. Paleoproterozoic carbonatites are closely associated with granulites and eclogites in orogens worldwide, playing a critical role in the Columbia supercontinent amalgamation and deep carbon cycle through time.

Effective Passivation and Tunneling Hybrid a-SiOx(In) Layer in ITO/n-Si Heterojunction Photovoltaic Device.

In this article, using controllable magnetron sputtering of indium tin oxide (ITO) materials on single crystal silicon at 100 °C, the optoelectronic heterojunction frame of ITO/a-SiOx(In)/n-Si is simply fabricated for the purpose of realizing passivation contact and hole tunneling. It is found that the gradation profile of indium (In) element together with silicon oxide (SiOx/In) within the ultrathin boundary zone between ITO and n-Si occurs and is characterized by X-ray photoelectron spectroscopy with the ion milling technique. The atomistic morphology and physical phase of the interfacial layer has been observed with a high-resolution transmission electron microscope. X-ray diffraction, Hall effect measurement, and optical transmittance with Tauc plot have been applied to the microstructure and property analyses of ITO thin films, respectively. The polycrystalline and amorphous phases have been verified for ITO films and SiOx(In) hybrid layer, respectively. For the quantum transport, both direct and defect-assisted tunneling of photogenerated holes through the a-SiOx(In) layer is confirmed. Besides, there is a gap state correlative to the indium composition and located at Ev + 4.60 eV in the ternary hybrid a-SiOx(In) layer that is predicted by density functional theory of first-principles calculation, which acts as an "extended delocalized state" for direct tunneling of the photogenerated holes. The reasonable built-in potential (Vbi = 0.66 V) and optimally controlled ternary hybrid a-SiOx(In) layer (about 1.4 nm) result in that the device exhibits excellent PV performance, with an open-circuit voltage of 0.540 V, a short-circuit current density of 30.5 mA/cm2, a high fill factor of 74.2%, and a conversion efficiency of 12.2%, under the AM 1.5 illumination. The work function difference between ITO (5.06 eV) and n-Si (4.31 eV) is determined by ultraviolet photoemission spectroscopy and ascribed to the essence of the built-in-field of the PV device. In addition, the strong inversion layer in the surface of the n-Si substrate is tentatively correlated to the a-SiOx(In) interface layer as well.

Recovery of an oxidized majorite inclusion from Earth's deep asthenosphere.

Minerals recovered from the deep mantle provide a rare glimpse into deep Earth processes. We report the first discovery of ferric iron-rich majoritic garnet found as inclusions in a host garnet within an eclogite xenolith originating in the deep mantle. The composition of the host garnet indicates an ultrahigh-pressure metamorphic origin, probably at a depth of ~200 km. More importantly, the ferric iron-rich majoritic garnet inclusions show a much deeper origin, at least at a depth of 380 km. The majoritic nature of the inclusions is confirmed by mineral chemistry, x-ray diffraction, and Raman spectroscopy, and their depth of origin is constrained by a new experimental calibration. The unique relationship between the majoritic inclusions and their host garnet has important implications for mantle dynamics within the deep asthenosphere. The high ferric iron content of the inclusions provides insights into the oxidation state of the deep upper mantle.

Origin of heavy rare earth mineralization in South China.

Heavy rare earth elements (HREE) are dominantly mined from the weathering crusts of granites in South China. Although weathering processes occur globally, no economic HREE resources of this type have yet been found outside China. Here, we report the occurrence of unidentified REE minerals in the granites from South Chinese deposits. They contain high levels of both HREE and light REE, but are strongly depleted in Ce, implying high oxidation state. These REE minerals show higher initial Nd isotope than primary REE-rich minerals (ɛNd(t)=0.9±0.8 versus -11.5±0.5). The mineralized weathering crusts inherited REE signature of the granites, but show more Ce depletion and more overall concentration of the REE. We propose, therefore, that highly oxidized, REE-rich fluids, derived from external, isotopically depleted sources, metasomatized the granites, which resulted in Ce depletion as Ce4+ and enrichment of the remaining REE, especially the HREE, contributing to formation of a globally important REE resource.

Origin of unusual HREE-Mo-rich carbonatites in the Qinling orogen, China.

Carbonatites, usually occurring within intra-continental rift-related settings, have strong light rare earth element (LREE) enrichment; they rarely contain economic heavy REE (HREE). Here, we report the identification of Late Triassic HREE-Mo-rich carbonatites in the northernmost Qinling orogen. The rocks contain abundant primary HREE minerals and molybdenite. Calcite-hosted fluid inclusions, inferred to represent a magmatic-derived aqueous fluid phase, contain significant concentrations of Mo (~17 ppm), reinforcing the inference that these carbonatitic magmas had high Mo concentrations. By contrast, Late Triassic carbonatites in southernmost Qinling have economic LREE concentrations, but are depleted in HREE and Mo. Both of these carbonatite types have low δ26Mg values (-1.89 to -1.07‰), similar to sedimentary carbonates, suggesting a recycled sediment contribution for REE enrichment in their mantle sources. We propose that the carbonatites in the Qinling orogen were formed, at least in part, by the melting of a subducted carbonate-bearing slab, and that 10 Ma younger carbonatite magmas in the northernmost Qinling metasomatized the thickened eclogitic lower crust to produce high levels of HREE and Mo.

Serum fatty acid profiles using GC-MS and multivariate statistical analysis: potential biomarkers of Alzheimer's disease.

Previous studies showed the relationship between fatty acids and the risk of developing Alzheimer's disease (AD). However, they did not address potential differences in free fatty acid (FFA) profiles that could be used to distinguish between AD patients and healthy controls. In the present study we used gas chromatography-mass spectrometry (GC-MS) technology coupled with multivariate statistical analysis to study profiles of FFA in AD. The results indicated 2 saturated fatty acids (C14:0 and C16:0; p < 0.001 and p < 0.05, respectively), 3 unsaturated fatty acids (C18:1, C18:3, and C22:6; p < 0.05, p < 0.05, and p < 0.001, respectively), where mean levels in serum from AD patients were significantly lower than controls. Partial least squares discriminant analysis (PLS-DA) models with unit variance (UV) scaling and orthogonal signal correction (OSC) data preprocessing methods were employed to refine intergroup differences between FFA profiles. The results of the analysis have highlighted docosahexaenoic acid (DHA) as the FFA with the greatest potential as a biomarker of AD, and this study has demonstrated that FFA biomarkers have considerable potential in diagnosing and monitoring AD.