Ultrafast piezocapacitive soft pressure sensors with over 10 kHz bandwidth via bonded microstructured interfaces.

Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

Photo/mechanical/acidic multi-stimuli responses and information encryption design of acylhydrazone derivative.

Stimuli-responsive crystalline materials have received much attention for being potential candidates of smart materials. However, the occurrence of polymorphism-driven stimuli responses in crystalline materials remains interesting but rare. Herein, three polymorphs of an acylhydrazone derivative, N'-[(E)-(1-benzofuran-2-yl) methylidene] pyridine -4-carbohydrazide (BFMP) were prepared. Form-1 undergoes a photomechanical response via E→Z photoisomerization under UV irradiation, accompanied by a decrease in fluorescence intensity and a change from colorless to yellow. Two types of Z→E thermal isomerization mechanisms with significant differences in conversion rate were observed at different temperatures in form-1. The solid-melt-solid transition has a faster conversion rate compared to the solid-solid transition due to freedom from lattice confinement. The transition from form-2 to form-3 can be achieved under grinding, coupled with a significant decrease in fluorescence intensity. The similar molecular stacking pattern of form-2 and form-3 provides a structural basis for the grinding-induced crystalline transition behavior. In addition, the presence of the pyridine moiety imparts an acid chromic property. The combination of photochromism and acid chromism explores the possible applications of acylhydrazone derivatives in information encryption.

Construction and analysis of a joint diagnostic model of machine learning for cryptorchidism based on single-cell sequencing.

BACKGROUND: Cryptorchidism is a condition in which one or both of a baby's testicles do not fully descend into the bottom of the scrotum. Newborns with cryptorchidism are at increased risk of developing infertility later in life. The aim of this study was to develop a novel diagnostic model for cryptorchidism and to identify new biomarkers associated with cryptorchidism. METHODS: The study data were obtained from RNA sequencing data of cryptorchid patients from Nantong University Hospital and the Gene Expression Omnibus (GEO) database. Differential expression analysis was used to obtain differentially expressed genes (DEGs) between the control and cryptorchid groups. These DEGs were analyzed for their functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using GSEA software. Random Forest algorithm was used to screen central genes based on these DEGs. Neuralnet software package was used to develop artificial neural network models. Based on clinical data, receiver operating characteristic (ROC) was used to validate the models. Single-cell sequencing analysis was used for the pathogenesis of cryptorchidism. RESULTS: We obtained a total of 525 important DEGs related to cryptorchidism, which are mainly associated with biological functions such as supramolecular complexes and microtubule cytoskeleton. Random forest approach screening obtained eight hub genes. A neural network based on the hub genes showed a 100% success rate of the model. Finally, single-cell sequencing analysis validated the hub genes. CONCLUSION: We developed a novel diagnostic model for cryptorchidism using artificial neural networks and validated its utility as an effective diagnostic tool.

Metal Ion-Regulated Fluorescent Sensor Array Based on Gold Nanoclusters for Physiological Phosphate Sensing.

The detection of physiological phosphates (PPs) is of great importance due to their essential roles in numerous biological processes, but the efficient detection of different PPs simultaneously remains challenging. In this work, we propose a fluorescence sensor array for detecting PPs based on metal-ion-regulated gold nanoclusters (AuNCs) via an indicator-displacement assay. Zn2+ and Eu3+ are selected to assemble with two different AuNCs, resulting in quenching or enhancing their fluorescence. Based on the competitive interaction of metal ions with AuNCs and PPs, the fluorescence of AuNCs will be recovered owing to the disassembly of AuNC-metal ion ensembles. Depending on different PPs' distinct fluorescence responses, a four-channel sensor array was established. The array not only exhibits good discrimination capability for eight kinds of PPs (i.e., ATP, ADP, AMP, GTP, CTP, UTP, PPi, and Pi) via linear discriminant analysis but also enables quantitative detection of single phosphate (e.g., ATP) in the presence of interfering PPs mixtures. Moreover, potential application of the present sensor array for the discrimination of different PPs in real samples (e.g., cell lysates and serum) was successfully demonstrated with a good performance. This work illustrates the great potential of a metal ion-regulated sensor array as a new and efficient sensing platform for differential sensing of phosphates as well as other disease-related biomolecules.

The Beaumont behavioral intervention in a Chinese amyotrophic lateral sclerosis cohort.

OBJECTIVE: The prevalence of behavior impairment (27.38%) in the Chinese amyotrophic lateral sclerosis (ALS) cohort is lower. We hypothesize that the screening scales used among studies might not be appropriate to diagnose behavioral disorders in ALS patients. So, we urgently need to find a behavior scale with a high detection rate designed specifically for ALS. This study aims to verify the Chinese translation of the Beaumont Behavioral Inventory (BBI) as an effective assessment in a Chinese ALS cohort. METHODS: Ninety-eighty ALS patients and ninety-three healthy controls were included in this cross-sectional study. All participants took emotional state, overall cognitive, sleep quality and gastroenteric function, and behavioral evaluation. RESULTS: The BBI scores showed a strong association with the amyotrophic lateral sclerosis-Frontotemporal Dementia-Questionnaire (ALS-FTD-Q) (rs = 0.71, p < 0.001) as well as a moderate correlation with the Frontal Behavioral Inventory (FBI) (rs = 0.55, p < 0.001). High internal consistency was demonstrated in patients using BBI-after items (Cronbach's a = 0.89). When tested against clinical diagnoses, the optimal cutoff of total BBI score was identified at 5.5 (AUC = 0.95; SE = 0.02; 95% CI [0.91, 0.99]), the BBI reached optimal sensitivity and specificity values (91.5% and 87.2%). The BBI turned out to be more precise than the FBI (AUC = 0.76; SE = 0.05; 95% CI [0.66, 0.86]) and the ALS-FTD-Q (AUC = 0.84; SE = 0.04; 95% CI [0.77, 0.92]). CONCLUSION: The Chinese version of BBI is a quicker and more efficient instrument for assessing behavioral impairment in the ALS population in China.

Genetic variation in targets of lipid-lowering drugs and amyotrophic lateral sclerosis risk: a Mendelian randomization study.

BACKGROUND: The use of lipid-lowering drugs is still highly controversial in patients with amyotrophic lateral sclerosis (ALS). We performed a drug-target Mendelian randomization (MR) analysis to investigate the effect of targeted lipid-lowering drugs on the risk of ALS. METHODS: First, we evaluated the causal relationship between HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (HMGCR) inhibitors-taking trait and ALS using a bidirectional two-sample MR study. Second, we investigated the causal relationship between lipid-lowering drugs and ALS through a drug-target MR approach. The summary data for HMGCR inhibitors-taking traits were extracted from a genome-wide association study (GWAS) of medication use and associated disease in the UK Biobank. The summary data for low-density lipoprotein cholesterol and apolipoprotein B (apoB) were extracted from a meta-analysis of GWAS in individuals of European ancestry in the UKB. The GWAS summary data of ALS were obtained from the Project MinE. RESULTS: Our bidirectional two-sample MR showed that genetically determined increased HMGCR inhibitors-taking trait was an independent risk factor for ALS (odds ratio [OR] = 1.090, 95% confidence interval [CI] = 1.035-1.150, p = 0.001). The results of drug-target MR showed that the increased expression of the HMGCR gene in blood with the higher risk of ALS (OR = 1.21, 95% CI = 1.01-1.46; p = 0.042) through SMR method and the apoB level mediated by the APOB gene increased the risk of ALS (OR = 1.15; 95% CI =1.05-1.25; p = 0.001) through inverse-variance weighted MR method. CONCLUSION: This present study provides genetic support for a positive causal effect of HMGCR inhibitors-taking trait and ALS. The reason for this may be due to the underlying disease condition behind the medication, rather than the medication itself. Our findings also suggested that HMGCR and apoB inhibitors may have potential protective effects on ALS.

Cortical structure and the risk of amyotrophic lateral sclerosis: A bidirectional Mendelian randomization study.

BACKGROUND: Current observational studies indicate progressive brain atrophy is closely associated with the clinical feature of amyotrophic lateral sclerosis. However, it is unclear whether the changes in cortical structure are the cause or result of ALS. Our study aimed to investigate the causal relationship between cortical structure and ALS risk using a bidirectional two-sample MR study. METHODS: We collected publicly available genome-wide association studies' summary statistics for cortical structure from UK Biobank and ENIGMA consortium (n = 33,992) and ALS from the Project MinE (n = 138,086). We used the inverse variance weighted method (IVW) as primary analysis in order to evaluate the causal effects. In addition, the weighted median and MR Egger methods were performed to ensure the robustness and reliability of the IVW results. RESULTS: We found the decreased surface of the paracentral lobule and thickness of the frontal pole and middle temporal lobe were suggestively associated with an increased risk of ALS as well as the increased surface of medial orbitofrontal and middle temporal lobe. In another aspect, the causalities between the susceptibility to ALS and the volume of the transverse temporal gyrus and superior temporal gyrus were negative. Besides, the susceptibility to ALS might also contribute to an increased thickness of the postcentral gyrus and superior parietal gyrus. CONCLUSION: In this two-sample MR analysis, we observed that multiple cortical brain regions are associated with a higher ALS risk. Further research into the underlying mechanisms is required to back up our findings.

Sleep Disturbances as a Potential Risk Factor for Deterioration of Respiratory Function in Patients with Amyotrophic Lateral Sclerosis.

Objectives: Sleep disturbances are common in amyotrophic lateral sclerosis (ALS). However, previous studies have explored sleep quality at the cross-sectional level and the longitudinal variability characteristics are currently unknown. Our study aimed to longitudinally explore the effect of sleep quality on disease progression in patients with ALS. Methods: All enrolled patients with ALS were first diagnosed and completed the 6- and 12-month follow-ups. Subjective sleep disturbance was assessed using the Pittsburgh Sleep Quality Index (PSQI). Based on the PSQI score at baseline, patients with ALS were classified as poor sleepers (PSQI >5) and good sleepers (PSQI ≤5). Disease progression was assessed using the rate of disease progression, the absolute change from baseline forced vital capacity (ΔFVC) and the percentage change from baseline FVC (ΔFVC%) over the follow-up period. Results: Sixty-three patients were included in the study, 24 (38.1%) were poor sleepers and 39 were good sleepers. The percentage of patients with poor sleep quality was 38.1% at baseline, increasing to 60.3% and 74.6% at 6- and 12-month, respectively. Compared to good sleepers, ΔFVC and ΔFVC% values were greater in poor sleepers (P < 0.001 and P = 0.001, respectively). Poor sleep quality at diagnosis is associated with rapid deterioration of respiratory function during disease progression. Conclusions: Sleep disturbances maybe a potential risk factor for deterioration of respiratory function in patients with ALS. The role of sleep disturbances in disease progression deserves attention, and early assessment and intervention may slow disease progression and improve life quality of patients with ALS.

Deep learning personalized recommendation-based construction method of hybrid blockchain model.

This study aims to explore the construction of a personalized recommendation system (PRS) based on deep learning under the hybrid blockchain model to further improve the performance of the PRS. Blockchain technology is introduced and further improved to address security problems such as information leakage in PRS. A Delegated Proof of Stake-Byzantine Algorand-Directed Acyclic Graph consensus algorithm, namely PBDAG consensus algorithm, is designed for public chains. Finally, a personalized recommendation model based on the hybrid blockchain PBDAG consensus algorithm combined with an optimized back propagation algorithm is constructed. Through simulation, the performance of this model is compared with practical Byzantine Fault Tolerance, Byzantine Fault Tolerance, Hybrid Parallel Byzantine Fault Tolerance, Redundant Byzantine Fault Tolerance, and Delegated Byzantine Fault Tolerance. The results show that the model algorithm adopted here has a lower average delay time, a data message delivery rate that is stable at 80%, a data message leakage rate that is stable at about 10%, and a system classification prediction error that does not exceed 10%. Therefore, the constructed model not only ensures low delay performance but also has high network security performance, enabling more efficient and accurate interaction of information. This solution provides an experimental basis for the information security and development trend of different types of data PRSs in various fields.

Wavefront shaping for multi-user line-of-sight and non-line-of-sight visible light communication.

Visible light communication (VLC) has become a popular method for indoor communication, due to its high transmission speed and robustness against electromagnetic interference. Indoor VLC scenarios commonly consist of multiple users in line-of-sight (LOS) and non-line-of-sight (NLOS) paths. In NLOS, the light waves suffer from attenuation due to diffuse reflection from obstacles in the room, leading to significant attenuation in light intensity. This paper proposes a wavefront shaping method to enhance indoor VLC for multiple users, including both LOS and NLOS. By employing a spatial division scheme, we can simultaneously achieve a light intensity gain of 5.43 dB in NLOS through stepwise partitioning wavefront shaping and an opening angle range of 27° for two LOS users through computational holography. By employing bit-power-loading discrete multi-tone (DMT) modulation, we demonstrated VLC with transmission data rates of 3.082 Gbit/s and 3.052 Gbit/s for two LOS links and 2.235 Gbit/s for NLOS with 30.7% improvement compared with that without wavefront shaping, satisfying the 7% forward-error-correction (FEC) threshold.

Novel low-sodium salt formulations combined with Chinese modified DASH diet for reducing blood pressure in patients with hypertension and type 2 diabetes: a clinical trial.

Background: In this study, we aimed to explore the antihypertensive effect of 23 and 52% concentrations of low-sodium salt combined with the Chinese Modified Dietary Approaches to Stop Hypertension (CM-DASH) diet in patients with hypertension and type 2 diabetes. Methods: We conducted a randomized controlled single-blind trial with a semi-open design. One hundred and thirty-two participants were randomly assigned into Group A (control group), Group B (52% low-sodium salt group), Group C (23% low-sodium salt group), and Group D (meal pack group) for 8 weeks of dietary intervention. All participants were followed weekly to collect data on blood pressure, salt use, and adverse events. Blood and 24-h urine samples were analyzed at baseline, 4 weeks, and the end of the intervention. Results: At the end of the intervention, the mean blood pressure decreased significantly by 10.81/5.03 mmHg, 14.32/6.32 mmHg, 14.20/6.59 mmHg, and 19.06/7.82 mmHg in Groups A-D, respectively, compared with baseline (p < 0.001). Comparison between groups showed that the systolic blood pressure was lower in Groups C and D than in Groups A (-6.54 mmHg, -8.70 mmHg, p < 0.05) and B (-6.60 mmHg, -8.76 mmHg, p < 0.05), and the diastolic blood pressure was lower in Group D than in Group A (-5.17 mmHg, p = 0.006). The 24-h urinary Na+ and Na+/K+ values were significantly decreased in participants using low-sodium salt (p < 0.001). No serious adverse events occurred during the trial. Conclusion: Our preliminary results suggest that 23 and 52% concentrations of low-sodium salt combined with the CM-DASH diet can effectively reduce sodium intake and increase potassium intake in patients with hypertension and type 2 diabetes mellitus, thus achieving "salt reduction" and attaining standard, smooth, comprehensive management of patients with hypertension and type 2 diabetes. Clinical trial registration: http://www.chictr.org.cn/, ChiCTR2000029017.

Gold Nanocluster-Based Fluorescent Microneedle Platform toward Visual Detection of ATP.

Adenosine triphosphate (ATP) participates in the regulation of most biological processes, and the ATP level is closely associated with many diseases. However, it still remains challenging to achieve on-site monitoring of ATP in an equipment-free and efficient way. Microneedles, a minimally invasive technology that can extract biomarkers from liquid biopsies, have recently emerged as useful tools for early diagnosis of a broad range of diseases. In this work, we developed hydrogel microneedles that are loaded with ATP-specific dual-emitting gold nanoclusters (RhE-AuNCs) for fast sampling and on-needle detection of ATP. These RhE-AuNCs were photo-crosslinked to the hydrogel matrix to form a fluorescent microneedle patch. Based on the ATP-induced Förster resonance energy transfer in RhE-AuNCs, a highly selective, sensitive, and reliable ATP sensor was developed. Moreover, simultaneous capture and visual detection of ATP was achieved by the AuNC-loaded microneedle sensing platform, which exhibits promising sensing performance. This work provides a new approach to design a point-of-care ATP sensing platform, which also holds great potential for the further development of microneedle-based analytical devices.

Race, Poverty, and Foster Care Placement in the United States: Longitudinal and Cross-Sectional Perspectives.

Although the connections between race, poverty, and foster care placement seem obvious, the link has not in fact been studied extensively. To address this gap, we view poverty and placement through longitudinal and cross-sectional lenses to more accurately capture how changes in poverty rates relate to changes in placement frequency. The longitudinal study examines the relationship between poverty rate changes and changes in the placement of Black and White children between 2000 and 2015. The cross-sectional study extends the longitudinal analysis by using a richer measure of socio-ecological diversity and more recent foster care data. Using Poisson regression models, we assess the extent to which changes in race-differentiated child poverty rates are correlated with Black and White child placement frequencies and placement disparities. Regardless of whether one looks longitudinally or cross-sectionally, we find that Black children are placed in foster care more often than White children. Higher White child poverty rates are associated with substantially reduced placement differences; however, higher Black child poverty rates are associated with relatively small changes in placement disparity. Black and White child placement rates are more similar in counties with the fewest socio-ecological assets.

Sleep disorders and white matter integrity in patients with sporadic amyotrophic lateral sclerosis.

This study aimed to explore the characteristics of sleep disorders and their relationship with abnormal white-matter integrity in patients with sporadic amyotrophic lateral sclerosis. One hundred and thirty-six patients and 80 healthy controls were screened consecutively, and 56 patients and 43 healthy controls were ultimately analyzed. Sleep disorders were confirmed using the Pittsburgh sleep quality index, the Epworth sleepiness scale, and polysomnography; patients were classified into those with poor and good sleep quality. White-matter integrity was assessed using diffusion tensor imaging and compared between groups to identify the white-matter tracts associated with sleep disorders. The relationship between scores on the Pittsburgh sleep quality index and impaired white-matter tracts was analyzed using multiple regression. Poor sleep quality was more common in patients (adjusted odds ratio, 4.26; p = 0.005). Compared to patients with good sleep quality (n = 30), patients with poor sleep quality (n = 26; 46.4%) showed decreased fractional anisotropy, increased mean diffusivity, and increased radial diffusivity of projection and commissural fibers, and increased radial diffusivity of the right thalamus. The Pittsburgh score showed the best fit with the mean fractional anisotropy of the right anterior limb of the internal capsule (r = - 0.355, p = 0.011) and the mean radial diffusivity of the right thalamus (r = 0.309, p = 0.028). We conclude that sleep disorders are common in patients with sporadic amyotrophic lateral sclerosis and are associated with reduced white-matter integrity. The pathophysiology of amyotrophic lateral sclerosis may contribute directly to sleep disorders.

Mutations in VWA8 cause autosomal-dominant retinitis pigmentosa via aberrant mitophagy activation.

BACKGROUND: Although retinitis pigmentosa (RP) is the most common type of hereditary retinal dystrophy, approximately 25%-45% of cases remain without a molecular diagnosis. von Willebrand factor A domain containing 8 (VWA8) encodes a mitochondrial matrix-targeted protein; its molecular function and pathogenic mechanism in RP remain unexplained. METHODS: Family members of patients with RP underwent ophthalmic examinations, and peripheral blood samples were collected for exome sequencing, ophthalmic targeted sequencing panel and Sanger sequencing. The importance of VWA8 in retinal development was demonstrated by a zebrafish knockdown model and cellular and molecular analysis. RESULTS: This study recruited a Chinese family of 24 individuals with autosomal-dominant RP and conducted detailed ophthalmic examinations. Exome sequencing analysis of six patients revealed heterozygous variants in VWA8, namely, the missense variant c.3070G>A (p.Gly1024Arg) and nonsense c.4558C>T (p.Arg1520Ter). Furthermore, VWA8 expression was significantly decreased both at the mRNA and protein levels. The phenotypes of zebrafish with VWA8 knockdown are similar to those of clinical individuals harbouring VWA8 variants. Moreover, VWA8 defects led to severe mitochondrial damage, resulting in excessive mitophagy and the activation of apoptosis. CONCLUSIONS: VWA8 plays a significant role in retinal development and visual function. This finding may provide new insights into RP pathogenesis and potential genes for molecular diagnosis and targeted therapy.

Bubble-blowing-inspired sub-micron thick freestanding silk films for programmable electronics.

Thin film electronics that are capable of deforming and interfacing with nonplanar surfaces have attracted widespread interest in wearable motion detection or physiological signal recording due to their light weight, low stiffness, and high conformality. However, it is still a challenge to fabricate freestanding thin film substrates or matrices with only sub-micron thickness in a simple way, especially for those materials with metastable conformations, like regenerated silk protein. Herein, we developed a dip-coating method for the fabrication of sub-micron thick freestanding silk films inspired by blowing soap bubbles. Using a closed-loop frame to dip-coat in a concentrated silk fibroin aqueous solution, the substrate-free silk films with a thickness as low as hundreds of nanometres (∼150 nm) can be easily obtained after solvent evaporation. The silk films have extremely smooth surfaces (Rq < 3 nm) and can be tailored with different geometric shapes. The naturally dried silk films possess random coil dominated uncrystallized secondary structures, exhibiting high modulation ability and adaptability, which can be conformally attached on wrinkled skin or wrapped on human hair. Considering the methodological advantages and the unique properties of the obtained sub-micron thick silk films, several thin film based programmable electronics including transient/durable circuits, skin electrodes, transferred skin light-emitting devices and injectable electronics are successfully demonstrated after being deposited with gold or conducting polymer layers. This research provides a new avenue for preparing freestanding thin polymer films, showing great promise for developing thin film electronics in wearable and biomedical applications.

Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Development and validation of a dynamic risk prediction system for constipation in patients with amyotrophic lateral sclerosis.

Introduction: Although constipation is a common non-motor symptom in patients with amyotrophic lateral sclerosis (ALS), it is poorly valued. Moreover, there is a bidirectional effect between constipation and neuropsychiatric and sleep disturbances. Thus, these symptoms are better treated simultaneously. Therefore, this study aimed to develop and validate a model for predicting the risk of constipation in ALS patients, to help clinicians identify and treat constipation early. Methods: Data of 118 ALS admissions from an observational prospective cohort, registered between March 2017 and December 2021, were analyzed. Demographic data were obtained. Constipation was assessed using the Knowles-Eccersley-Scott Symptom Questionnaire. The severity of ALS was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The Pittsburgh Sleep Quality Index (PSQI) was used to assess patients' sleep status. The least absolute shrinkage and selection operator (LASSO) regression model was used to select factors and construct a nomogram. Nomogram model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). The model was internally validated using bootstrap validation in the current cohort. Results: Age, family history of constipation, total ALSFRS-R score, site of onset, total PSQI score, and depressed, were identified as significant predictors of the risk of constipation in ALS patients. The prediction model was validated to have good accuracy (Hosmer-Lemeshow test: χ2 = 11.11, P > 0.05) and discrimination (AUC = 0.856, 95% confidence interval: 0.784-0.928). DCA and CIC showed that the nomogram model had excellent clinical performance. Conclusions: A web-based ALS constipation risk calculator with good predictive performance was constructed to identify patients at high risk of constipation and to allow early intervention in a clinical context.

Formaldehyde Decomposition from -20 °C to Room Temperature on a Mn-Mullite YMn2O5 Catalyst.

Large ambient temperature changes (-20->25 °C) bring great challenges to the purification of the indoor pollutant formaldehyde. Within such a large ambient temperature range, we herein report a manganese-based strategy, that is, a mullite catalyst (YMn2O5) + ozone, to efficiently remove the formaldehyde pollution. At -20 °C, the formaldehyde removal efficiency reaches 62% under the condition of 60,000 mL gcat-1 h-1. As the reaction temperature is increased to -5 °C, formaldehyde and ozone are completely converted into CO2, H2O, and O2, respectively. Such a remarkable performance was ascribed to the highly reactive oxygen species generated by ozone on the YMn2O5 surface based on the low temperature-programed desorption measurements. The in situ infrared spectra showed the intermediate product carboxyl group (-COOH) to be the key species. Based on the superior performance, we built a consumable-free air purifier equipped with mullite-coated ceramics. In the simulated indoor condition (25 °C and 30% relative humidity), the equipment can effectively decompose formaldehyde (150 m3 h-1) without producing secondary pollutants, rivaling a commercial removal efficiency. This work provides an air purification route based on the mullite catalyst + ozone to remove formaldehyde in an ambient temperature range (-20->25 °C).

The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants.

BACKGROUND: Dysferlinopathy is an autosomal recessive muscular dystrophy caused by pathogenic variants in the dysferlin (DYSF) gene. This disease shows heterogeneous clinical phenotypes and genetic characteristics. METHODS: We reviewed the clinical and pathological data as well as the molecular characteristics of 26 Chinese patients with dysferlinopathy screened by immunohistochemistry staining and pathogenic variants in DYSF genes. RESULTS: Among 26 patients with dysferlinopathy, 18 patients (69.2%) presented as Limb-girdle Muscular Dystrophy Type R2 (LGMD R2), 4 (15.4%) had a phenotype of Miyoshi myopathy (MM), and 4 (15.4%) presented as asymptomatic hyperCKemia. Fifteen patients (57.7%) were originally misdiagnosed as inflammatory myopathy or other diseases. Fifteen novel variants were identified among the 40 variant sites identified in this cohort. CONCLUSION: Dysferlinopathy is a clinically and genetically heterogeneous group of disorders with various phenotypes, a high proportion of novel variants, and a high rate of misdiagnosis before immunohistochemistry staining and genetic analysis.