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Background: Colony‐stimulating factor 1 receptor (CSF1R)‐related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. Objective: The objective of the study is to clarify the core features and influence factors of CRD patients in China. Methods: Clinical and genetic‐related data of CRD patients in China were collected. Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. Results: A total of 103 patients were included, with a male‐to‐female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. Conclusions: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Aim: To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS‐7535, a novel glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), in healthy participants. Materials and Methods: This phase 1 trial consisted of single‐ascending dose (SAD), food effect (FE) and multiple‐ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS‐7535 (at doses of 15, 60 and 120 mg; administered orally once daily) or placebo. In the FE part, participants were randomized (8:2) to receive a single dose of 90‐mg HRS‐7535 or placebo, in both fed and fasted states. In the MAD part, participants were randomized (18:6) to receive daily HRS‐7535 (120 mg [30/60/90/120‐mg titration scheme]) or placebo for 28 days. The primary endpoints were safety and tolerability. Results: Nausea and vomiting were the most frequently reported AEs across all three parts. In the SAD part, the median Tmax was 5.98‐5.99 hours and the geometric mean t1/2 was 5.28‐9.08 hours across the HRS‐7535 dosing range. In the MAD part, the median Tmax was 5.98‐10.98 hours and the geometric mean t1/2 was 6.48‐8.42 hours on day 28 in participants on HRS‐7535. PKs were approximately dose‐proportional. On day 29 in the MAD part, the mean (percentage) reduction in body weight from baseline was 4.38 kg (6.63%) for participants who received HRS‐7535, compared with 0.8 kg (1.18%) for those participants who received a placebo. Conclusions: HRS‐7535 exhibited a safety and tolerability profile consistent with other GLP‐1RAs and showed PKs suitable for once‐daily dosing. These findings support further clinical development of HRS‐7535 for type 2 diabetes. [ABSTRACT FROM AUTHOR]

1Radiological, pathological and genetic characteristics of AARS1 -AR-ALSP, CSF1R -ALSP and AARS2 -ALSP. a-g Sagittal and transverse view of neuroimaging. h-n Immunohistochemistry of brain biopsy. An AARS1 variant identified to cause adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia I AARS1 i -AR-ALSP patients are also featured with posterior-predominant leukoencephalopathy, relatively mild pathological changes and neuroinflammation level, and hypoalbuminemia likely related to marasmus and malnutrition. Later, variants in I AARS2 i (encoding alanyl-transfer tRNA synthetase 2) were found pathogenic for autosomal recessive ALSP patients ( I AARS2 i -ALSP) [[2]]. [Extracted from the article]

In recent years, hyperspectral (HS) sharpening technology has received high attention and HS sharpened images have been widely applied. However, the quality assessment of HS sharpened images has not been well addressed and is still limited to the use of full-reference quality evaluation. In this paper, a novel no-reference quality assessment method based on Benford's law for HS sharpened images is proposed. Without a reference image, the proposed method detects fusion distortion by performing first digit distribution on three quality perception features in HS sharpened images, using the standard Benford's law as a benchmark. The experiment evaluates 10 HS fusion methods on three HS datasets and selects four full-reference metrics and four no-reference metrics to compare with the proposed method. The experimental results demonstrate the superior performance of the proposed method. [ABSTRACT FROM AUTHOR]

Background: GGC repeat expansions in NOTCH2NLC gene have been recently proposed to cause neuronal intranuclear inclusion disease (NIID) via prevailing gain-of-function mechanism (protein and RNA toxicity). Nevertheless, increasing evidences suggest that epigenetics can also play a role in the pathogenesis of repeat-mediated disorders. Methods: In this study, using MethylTarget sequencing, we performed a quantitative analysis of the methylation status of 68 CpG sites located around the NOTCH2NLC promoter in 25 NIID patients and 25 age- and gender-matched healthy controls. We further explored the correlation of DNA methylation (DNAm) status with disease features and performed receiver operating characteristic (ROC) analysis. Results: DNAm levels of GGC repeats and adjacent CpG islands were higher in the NIID patients than in controls, independent of gender and family history. DNAm levels at 4 CpG sites (CpG_207, CpG_421, GpG_473 and CpG_523) were negatively correlated with age at onset, and DNAm levels at 7 CpG sites (CpG_25, CpG_298, CpG_336, CpG_374, CpG_411, CpG_421 and CpG_473) were positively correlated with GGC repeats. NIID patients had concomitant system symptoms besides nervous system symptoms, and negative correlations between NOTCH2NLC DNAm levels and the number of multi-systemic involvement were observed in the study. The area under the ROC curve at NOTCH2NLC DNAm level reached to 0.733 for the best cutoff point of 0.012. Conclusions: Our findings suggested the aberrant DNAm status of the NOTCH2NLC promoter in NIID, and we explored the link between DNAm levels and disease features quantitatively for the first time, which may help to further explore pathogenic mechanism. [ABSTRACT FROM AUTHOR]

The dynamic stability of dense medium suspension is the premise to ensure the effective separation of mineral particles in the separation equipment. It is usually difficult to directly measure the dynamic stability of the suspension in the separation process of the dense medium cyclone. In this paper, a parameter defined as the density difference value between the underflow and overflow of cyclone is used to characterize the dynamic stability of the suspension in the separation process. Under the conditions of different operating parameters and structural parameters, the influencing factors of the dynamic stability of 1.30–1.60 g/cm3 dense medium suspension are systematically studied. The results show that the parameter value is in the range of 0.20–0.50 g/cm3, which is conducive to the separation of particles. When the suspension density increases, the characteristic value of density difference decreases, the influence of the suspension density, feed pressure, the diameter of underflow and overflow port diameter on the density difference characteristic are also researched. Eventually, the formula for calculating the density difference of the characteristic value of suspension is derived. [ABSTRACT FROM AUTHOR]

Excessive uric acid levels may affect several organs and systems in the body. There is limited evidence of the effects of high serum uric acid levels on the female reproductive system. This study used the National Health and Nutrition Examination Survey (NHANES) database to explore the relationship between serum uric acid and female infertility. This cross-sectional study included a total of 2197 eligible subjects using data from NHANES 2013-March 2020 pre-pandemic data. Self-reported infertility (ever experiencing an inability to conceive after 12 months of trying to become pregnant) was the main outcome. Logistic regression models and restricted cubic spline were used to analyze the relationship between serum uric acid and female infertility, and stratified analysis was carried out. A total of 295 women self-reported infertility (13.43%). The median uric acid level for all study subjects was 4.4 mg/dL (interquartile range [IQR]: 3.7, 5.1). Serum uric acid levels were higher in the infertility group than in the control group (4.7 mg/dL [IQR: 4.0, 5.3] vs. 4.4 mg/dL [IQR: 3.7, 5.1], P < 0.001). After adjusting for age, race, marital status, smoking, alcohol, history of pregnancy, history of diabetes, history of hypertension, fasting glucose, total cholesterol, creatinine in refrigerated serum, low-density lipoprotein cholesterol, direct high-density lipoprotein cholesterol, glycohemoglobin, and body mass index confounders, women with serum uric acid levels at Q3 (4.4–5.1 mg/dL) had a 73% (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.18, 2.54, P = 0.005) higher risk of infertility, and women with uric acid levels at Q4 (5.1–18.0 mg/dL) had an 83% (OR = 1.83, 95% CI 1.22, 2.75, P = 0.003) increased risk of infertility compared to women at Q1 (1.6–3.7 mg/dL). The restricted cubic spline also showed that when serum uric acid levels exceeded the reference value, the risk of infertility gradually increased. We also performed a sensitivity analysis based on the complete dataset and found that the results were robust. Higher serum uric acid levels were significantly associated with an increased risk of female infertility. Women planning a pregnancy should have increased serum uric acid monitoring. [ABSTRACT FROM AUTHOR]

Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes. Herein, detailed clinical investigation of 2 Chinese patients from two unrelated families were described, both of them showed mildly delay in developmental milestone before disease onset, the initial symptoms were all presented with acute motor and mental retrogression, and brain MRI showed diffused leukoencephalopathy with cavities, dysplasia of corpus callosum and cerebral atrophy. Exome sequencing revealed three IBA57 variants, one shared variant (c.286T>C) has been previously reported, the remaining two (c.189delC and c.580 A>G) are novel. To enhance the understanding of this rare disease, we further made a literature review about the current progress in clinical, genetic and treatment of the disorder. Due to the rapid progress of MMDS, early awareness is crucial to prompt and proper administration, as well as genetic counseling. [ABSTRACT FROM AUTHOR]

Background: The differences in the clinical and functional outcomes of closed reduction and percutaneous pin fixation and open reduction with internal fixation (ORIF) using plate and screws have been systematically synthesized by one meta-analysis. With newer studies being published, an effort to update the earlier meta-analysis is necessary. Methods: Comprehensive searches were done systematically through PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases. Randomized controlled trials, quasi-experimental studies, prospective comparative non-randomized studies, and even studies reporting findings from retrospective chart review were eligible to be included. Statistical analysis was done using STATA version 13.0. GRADE assessment was done to assess the quality of pooled evidence. Results: A total of 9 studies were included. The pooled estimates did not suggest any significant differences in the disabilities of the arm, shoulder, and hand (DASH) score [WMD − 0.77; 95% CI, − 3.55, 2.00; I2 = 75.5%], range of movement (ROM) of the metacarpophalangeal joint (o) [WMD 4.44; 95% CI, − 4.19, 13.07; I2 = 86.0%], and grip strength [WMD − 4.63; 95% CI, − 14.52, 5.26; I2 = 86.9%] among the two intervention modalities. No difference was seen in the risk of complications between the two interventions (RR 0.93; 95% CI, 0.57, 1.53; I2 = 31.2%). For all the outcomes, the quality of pooled evidence was judged as low to very low. Conclusion: No significant long-term differences were noted in the functional outcomes suggesting that both these techniques are comparable. The choice of modality should be made based on the skills and preference of the surgeon and availability of resources. [ABSTRACT FROM AUTHOR]

A underwater wireless optical communication (UWOC) system using a multi-pixel photon counter (MPPC) as the receiver and orthogonal frequency division multiplexing (OFDM) was proposed and experimentally investigated. The MPPC with high sensitivity combined with quadrature amplitude modulation (QAM) OFDM with high spectral efficiency can potentially support a data rate of hundreds of Mbps under a relatively long underwater transmission distance. Although the photoelectric response of each individual pixel in the MPPC is nonlinear due to its intrinsic dead time, the MPPC consisting of thousands of pixels can be operated like a linear photodetector due to the statistical effect. A net data rate of 312.03 Mbps, with a bit error rate (BER) below the forward error correction (FEC) limit, was successfully achieved over a 21-m underwater channel exploiting 32-QAM OFDM modulation. [ABSTRACT FROM AUTHOR]

Abstract Presently, most of the long-reach underwater wireless optical communication (UWOC) systems employ laser diodes rather than light-emitting diodes (LEDs) as the transmitters. Due to lasers' smaller divergence angles, those UWOC systems could realize longer communication links. Although LED-based long-reach UWOC has distinguished advantages, it suffers from very low received optical power. Fortunately, highly sensitive multi-pixel photon counter (MPPC) and energy efficient pulse position modulation (PPM) pave a way towards LED-based long-reach UWOC. In this paper, we investigated the underlying working principle of an MPPC and proposed a UWOC system based on single LED as well as a lens-free MPPC with digital output. The relationship between the MPPC p.e. threshold and its received optical power was theoretically studied and further proved by experimental results. Single 2.3-MHz, 3-W blue LED was used as the transmitter to generate 8-PPM to 64-PPM signals with a 5-MHz slot frequency. After a 46-m underwater transmission, the measured BERs were all below the forward error correction (FEC) limit, which were achieved with less than 100 incident photons during each pulse slot. [ABSTRACT FROM AUTHOR]

The conventional approaches for recovering valuable metals from spent lithium-ion batteries (LIBs) suffer from heavy dependence on chemical reagents, high energy consumption, and low recovery efficiencies. In this study, we developed a shearing-enhanced mechanical exfoliation combined with mild-temperature pretreatment (SMEMP) method. The method achieves high-efficiency exfoliation of the cathode active materials that remain strongly adhered to polyvinylidene fluoride after it melts during mild pretreatment. The pretreatment temperature was decreased from 500–550 °C to 250 °C, the duration was decreased to 1/4–1/6 of the traditional pretreatment duration, and the exfoliation efficiency and product purity reached 96.88% and 99.93%, respectively. Despite the weakening thermal stress, the cathode materials could be exfoliated by strengthened shear forces. Compared with other traditional methods, the superiority of this method in temperature reduction and energy saving was established. The proposed SMEMP method is environmentally friendly and economical, and it offers a new route for the recovery of cathode active materials from spent LIBs. [Display omitted] • A shearing-enhanced exfoliation method combined with mild pretreatment is proposed. • The exfoliation was achieved by synergy of thermal stress and strong shear action. • Heat treatment temperature dropped by about 250 °C with the duration reduced to 1/6. • The exfoliating efficiency could reach 96.88% with purity as high as 99.93%. [ABSTRACT FROM AUTHOR]

The reproductive toxicity of perfluoroalkyl and polyfluoroalkyl substances (PFAS) has been verified in both animal and in vitro experiments, however, the association between PFAS and female fertility remains contradictory in population studies. Therefore, in this systematic review and meta-analysis, we evaluated the effects of PFAS on female fertility based on population evidence. Electronic searches of the Web of Science, PubMed, The Cochrane Library, and Embase databases were conducted (from inception to March 2022) to collect observational studies related to PFAS and female fertility. Two evaluators independently screened the literature, extracted information and evaluated the risk of bias for the included studies, meta-analysis was performed using R software. A total of 5468 records were searched and 13 articles fully met the inclusion criteria. Meta-analysis showed that perfluorooctanoic acid (PFOA) exposure was negatively associated with the female fecundability odds ratio (FOR = 0.88, 95% confidence interval (Cl) [0.78; 0.98]) and positively associated with the odds ratio for infertility (OR = 1.33, 95%Cl [1.03; 1.73]). Perfluorooctane sulfonate (PFOS) exposure was negatively associated with the fecundability odds ratio (FOR = 0.94, 95% CI [0.90; 0.98]). Pooled effect values for perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorohexane sulfonate (PFHxS) exposure did not find sufficient evidence for an association with female fertility. Based on the evidence provided by the current study, increased levels of PFAS exposure are associated with reduced fertility in women, this was characterized by a reduction in fecundability odds ratio and an increase in odds ratio for infertility. This finding could partially explain the decline in female fertility and provide insight into risk assessment when manufacturing products containing PFAS. [ABSTRACT FROM AUTHOR]

• A new framework is proposed for the ecological efficiency of nitrogen use analysis. • A new indicator is set up for the ecological efficiency of nitrogen use assessment. • The ecological efficiency of nitrogen use was averagely 48.2% in Jianghan Plain. • The improvement of the ecological efficiency of nitrogen use was discussed. The concepts of nitrogen use efficiency were mainly conceived within the disciplinary boundaries, which were mostly bound to the nitrogen uptake instead of nitrogen loss. It frequently caused policy distortion. Aiming at evaluating the ecological efficiency analysis of nitrogen use from the perspective of nitrogen loss and in the context of nitrogen cycling, this paper proposed a new framework for nitrogen use efficiency analysis, which divided the total applied nitrogen into three parts, including the uptake nitrogen, the inevitably lost nitrogen and the overused nitrogen. A new indicator of the ecological efficiency of nitrogen use (EENU) was defined and calculated with coupling methods of agronomy and economics with the surveyed data of the rice production in Jianghan Plain. Results showed that the uptake nitrogen, the inevitably lost nitrogen and the overused nitrogen were 31%, 27% and 42% of the total applied nitrogen, i.e. 74.1 kg/ha, 59.0 kg/ha and 101.7 kg/ha, respectively. The EENU ranged from 18.8% to 88.1% with an average of 48.2%, implying that the environmental damage resulting from nitrogen loss could be decreased up to 51.8% in rice production in Jianghan Plain, which was about 88.3 kg/ha nitrogen. The soil's capacity of nitrogen supply and the technical efficiency of crop production would greatly influence the ecological efficiency of nitrogen use. The inevitably lost nitrogen was highly positively related to the soil's capacity of nitrogen supply. The nitrogen loss could be decreased when the nitrogen fertilizer was utilized to sustain the soil's nitrogen supply capacity. Many economic factors would also influence the ecological efficiency of nitrogen use by impacting the technical efficiency of the farmers' production. The technical efficiency of rice production was 0.82 in Jianghan Plain. The overused nitrogen and its loss could be greatly decreased while the technical efficiency was improved. [ABSTRACT FROM AUTHOR]