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1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond.

Aim: Located hundreds of kilometres offshore of continental mainland Asia, the extremely high level of land vertebrate endemism in the East Asian Island Arc provides an excellent opportunity to test hypotheses regarding biogeographic processes and speciation. In this study, we aim to test alternative explanations for lineage diversification (vicariance versus dispersal models), and further develop a temporal framework for diversification in our focal taxon, which is consistent with the known age of these islands. We achieve these tests by investigating the historical biogeography of the Okinawa tree lizard (Japalura polygonata), one of the few widely-distributed reptiles across this archipelago. Location: The East Asian Island Arc: (1) Central Ryukyu (Amami and Okinawa groups); (2) Southern Ryukyu (Miyako and Yaeyama groups); (3) Taiwan and adjacent islands. Methods: A total of 246 tissues were sampled from 10 localities in the Ryukyu archipelago and 17 localities in Taiwan, covering the entire distributional range of this species, including all subspecies. DNA sequences of the mitochondrial cytochrome b, 16S ribosomal RNA, nuclear BACH-1 and RAG-1 genes (total: 4,684 bp) were obtained from these samples. We used maximum likelihood and Bayesian methods to infer phylogeny and divergence time, and used a model-fitting method of biogeographical inference to estimate ancestral range evolution. Results: Multiple lines of evidence combine to identify a general pattern of dispersal-mediated diversification northward through the archipelago, following initial dispersal from Taiwan. These included (1) a phylogenetic estimate, revealing a sequential, south-to-north branching pattern; (2) ancestral range estimation, inferring multiple overseas dispersals and subsequent colonization of new landmasses; and (3) a reduction in genetic variation observed in successively-diverging lineages, decreasing from Taiwan northward, towards more remote islands. These results provide strong statistical support for an interpretation of successive bouts of dispersal via the powerful, well-documented, south-to-north Kuroshio Current. Estimation of divergence times suggests that most clades in southern Ryukyu and Taiwan diverged early, giving rise to lineages that have remained isolated, and that more recently-diverged lineages then colonized northward to subsequently occupy the landmasses of the Central Ryukyu archipelago. Main conclusions: Our general inference of biogeographic history in Japalura polygonata suggested that this species originated on Taiwan and the Yaeyama group, and arrived at its current distribution in Miyako, Okinawa, Toku and Amami islands by a series of stepping-stone dispersals, which we report for the first time for a terrestrial vertebrate endemic to this region.

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression. Alzheimer’s disease: A new biomarker for disease progression? Molecular tests built around analyzing B cells, a specialized type of immune cell, could aid in the diagnosis of Alzheimer’s disease. Liu-Lin Xiong from the Affiliated Hospital of Zunyi Medical University, China, and coworkers used single-cell RNA sequencing to profile gene activity in individual peripheral blood mononuclear cells from people with and without Alzheimer’s disease. They discovered that people with Alzheimer’s, especially those with more advanced disease, had lower levels of circulating B cells than healthy subjects. Twenty-five specific genes in the B cells were expressed at significantly higher or lower levels as the disease progressed. The researchers found similar results regarding B cells and Alzheimer’s progression in mouse models, and showed that massive depletion of B cells in the early onset was associated with accelerated cognitive decline and increased accumulation of sticky brain plaques.

Background The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS. Methods The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646. Results A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1 , TARDBP , TBK1 , NEK1 , UBQLN2 , and CCNF . In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS. Conclusions Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.

In the English as a foreign language (EFL) writing context, most of the research studies on the feedback process are conducted in a face-to-face context and few research studies have been conducted to investigate what actually happens in online feedback conditions. Thus, this study aimed to compare 44 EFL university students’ experience of employing asynchronous peer feedback (APF) and synchronous corrective feedback (SCF) and whether the utilization of these two modes affected EFL students’ writing on the aspect of syntactic complexity. The major findings suggested that most participants accepted this e-learning revision approach and received satisfactory results via using APF and SCF modes. The feedback that occurred in APF was potentially more usable than that in SCF in writing more sentences. It is assumed that as students added more words, they increased their writing scores after using APF. Although learners generally accepted both online feedback modes, the interview results revealed some of the reasons for learners’ preference for the APF over the SCF mode. Finally, the implications of these findings for future research are discussed and presented.

Sophora japonica L. is widely consumed in China because of its medicinal and nutritional value. Its quality is greatly affected by the accumulation of metabolites, which varies with the stage of flower development. However, changes in the characteristics of the secondary metabolites during flower maturity remain unclear. Ultra-high-performance liquid chromatography coupled with electrospray ionization-triple quadrupole-linear ion trap mass spectrometry (UPLC–ESI–QTRAP–MS/MS) revealed dynamic changes in the secondary metabolites of S. japonica during the five flower-maturity stages. We monitored 331 metabolites and screened 164. The differential metabolites showed seven trends during flower maturation, with flavonoids and phenolic acids having the most varied expressions. Flower buds (S2–S3) are rich in flavonoids and are thus suitable for use in high-quality medicine or industrial extraction. Our study provides an empirical basis for the informed harvesting of S. japonica based on its mode of utilization.

The hydroxyl radical (OH), as the central atmospheric oxidant, controls the removal rates of methane, a powerful greenhouse gas. It is being suggested that OH levels would decrease with reductions of nitrogen oxides and ozone levels by climate polices, but this remains unsettled. Here, we show that driven by the carbon neutrality pledge, the global-mean OH concentration, derived from multiple chemistry-climate model simulations, is projected to be significantly increasing with a trend of 0.071‒0.16% per year during 2015–2100. The leading cause of this OH enhancement is dramatic decreases in carbon monoxide and methane concentrations, which together reduce OH sinks. The OH increase shortens methane’s lifetime by 0.19‒1.1 years across models and subsequently diminishes methane’s radiative forcing. If following a largely unmitigated scenario, the global OH exhibits a significant decrease that would exacerbate methane’s radiative forcing. Thus, we highlight that targeted emission abatement strategies for sustained oxidation capacity can benefit climate change mitigation in the Anthropocene. Atmospheric chemistry-climate model projections reveal an increase in global hydroxyl radical concentrations on the path toward carbon neutrality in the 21st century. This consequently benefits methane mitigation.

The goaf formed by mining and other activities is prone to safety hazards. Preparing high-quality and low-cost solidified iron tailings powder (SITP) is an important way to ensure backfill quality and eliminate safety hazards. Using iron tailings powder near the goaf of in Shanxi, comparative experiments were conducted to evaluate the the flowability, stone rate, strength, and water stability of newly mixed SITP under different types and dosages of curing agent, and mixing methods. The results show that under the premise of keeping the fluidity constant, the strength of the ITP slurry increases with the increase of the curing agent content; At the same strength, the water consumption significantly affects the fluidity; When using 8%~16% different curing agent dosage, the expansion degree is 280 mm ~ 600 mm, the wet density is 1.9 g/cm 3  ~ 2.1 g/cm 3 , the 28d strength after curing is 1.4 MPa ~ 3.7 MPa, and the stone rate is greater than 92%; The ITP slurry prepared by vibration mixing with a mixing time of 120 s and the amount of curing agent at 8% meets the engineering application requirements of 7d strength of 0.6 MPa and expansion of 250 mm. The research shows that the iron tailings powder slurry prepared by vibration mixing has high strength after solidification, and it is a new way of resource utilization of iron tailings powder with large consumption and good economy to be used for goaf backfilling.

Background The nature and frequency of nonmotor symptoms in primary adult‐onset cervical dystonia (CD) and blepharospasm (BSP) patients in Chinese populations remain unknown. Methods Hamilton's Depression Scale (HAMD), Hamilton's Anxiety Scale (HAMA), Addenbrooke's Cognitive Examination Revised (ACE‐R), Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale were used to evaluate NMS in 120 patients with primary focal adult‐onset dystonia (60 with BSP and 60 with CD) and 60 age‐, sex‐, and education level‐ matched healthy controls (HCs). Motor symptoms of BSP and CD patients were evaluated by Jankovic rating scale and Toronto Western Spasmodic Torticollis Rating Scale‐severity scale separately. Results Twenty patients had depression, and 29 patients had anxiety. The mean HAMD and HAMA scores were significantly higher in patient groups. Thirty‐six patients had cognitive decline based on the cut‐off score of 75. The total score and scores of each domain of ACE‐R were significantly lower in patient groups than that in HCs. Quality of sleep was impaired in patient groups, and patients with CD had worse quality of sleep than patients with BSP. Thirty‐three BSP patients and 43 CD patients suffered from sleep disorder separately. The frequency of excessive daytime sleepiness did not differ between patients and HCs. No significant correlation was found between NMS and motor severity in the two forms of dystonia. Conclusions Current study suggests that NMS are prevalent in Chinese CD and BSP patients, and the motor severity of dystonia did not contribute to the severity of nonmotor symptoms. Assessment of nonmotor symptoms should be considered in clinical management of focal dystonia Patients with dystonia may develop several nonmotor symptoms (NMS). NMS were evaluated in 120 patients with cervical dystonia and blepharospasm. We found depression, anxiety, sleep disorder and cognitive decline are common in these patients, and the severity of motor symptom did not contribute to the severity of NMS in craniocervical dystonia.

Studies have reported that non-motor symptoms are an important component of primary dystonia. However, evidence supporting cognitive impairment in primary dystonia is limited and contradictory. We applied the Chinese version of the Addenbrooke's Cognitive Examination-Revised and the Mini-Mental State Examination (MMSE) to screen for cognitive impairment in patients with primary blepharospasm. In addition, we investigated the relationship between performance on the Addenbrooke's Cognitive Examination-Revised and quality of life as measured by the Medical Outcomes Study 36-item Short-Form (SF36). The study included 68 primary blepharospasm patients and 68 controls matched by age, sex and education. The prevalence of cognitive deficits was 22.0% and 32.3% in primary blepharospasm patients group, as measured by the MMSE and the Addenbrooke's Cognitive Examination-Revised, respectively. Primary blepharospasm patents had a broad range of cognitive deficits, with the most frequently affected domains being visuospatial function (30.9%) and language (30.9%), followed by memory (27.9%), orientation/attention (26.4%) and verbal fluency (22.0%). Patients with cognitive deficits had lower total SF36 scores, especially in the subdomains of physical functioning, role-physical and social functioning, compared to those without cognitive deficits. Scores on the Addenbrooke's Cognitive Examination-Revised were significantly correlated with both the SF36 scores and the scores on the subdomains of physical functioning and social functioning. Some patients with primary blepharospasm have cognitive deficits. Poor performance on the Addenbrooke's Cognitive Examination-Revised is related to poorer quality of life.