A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene. METHODS AND RESULTS: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site. CONCLUSION: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Cognitive impairment and depression precede increased HDL-C levels in middle-aged and older Chinese adults: cross-lagged panel analyses.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. METHODS: The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. RESULTS: The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (ß = - 0.036 and ß = 0.028, respectively, P < 0.05). However, higher baseline HDL-C levels did not significantly predict cognitive performance or depression 4 years later (ß = - 0.008 and ß = 0.023, respectively, P > 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (ß = - 0.026 and ß = - 0.053, respectively, P < 0.05). CONCLUSIONS: Cognitive impairment and depression are associated with higher HDL-C levels, whereas higher HDL-C levels do not appear to protect against cognitive decline or depressive symptoms. These findings underscore the importance of preserving cognitive and mental health, which may lower the likelihood of cardiovascular disease and dementia. Future studies should validate these findings and develop targeted interventions tailored to specific populations.

[Analysis of the Effects of Femoral Nerve Block on Pain Level and Knee Mobility in Patients With Total Knee Replacement].

BACKGROUND: Osteoarthritis is a common cause of inactivity and reduced quality of life in the elderly. Total knee replacement (TKR) surgery, a last-stage treatment option for osteoarthritis, often results in postoperative pain that influences knee flexion and the ability to perform prescribed rehabilitation exercises. PURPOSE: This study was designed to examine the effectiveness of single femoral nerve block (FNB) on pain level and knee mobility in patients with TKR. METHODS: A quasi-experimental, two-group, longitudinal study was designed. The participants were distributed into the FNB group (n = 86) and non-FNB group (n = 86). The outcome measurements included pain scale (Numerical Rating Scale) score and knee continuous passive motion knee flexion angle. The five assessments and followed-up times were as follows: admission day (T0) and post-surgery day 1, 2, 3, and 4. RESULTS: The results of the generalized estimating equations model showed that the pain level in the FNB group was significantly lower than in the non-FNB group, (p < .001). In terms of analgesics demand from post-surgery day 1 to day 4, the FNB group exhibited a significantly lower demand than the non-FNB group (p < .01). In addition, significant differences in the continuous passive motion rehabilitation exercise angle were found between the two groups from post-surgery day 1 through day 4 (p < .05). Finally, significant differences in knee flexion angles between the two groups were observed between hospital admission and discharge (p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study support the positive effects of the femoral nerve block intervention on patients who receive total knee replacement surgery. The results were significant in terms of pain relief and knee mobility recovery. This intervention should be made available for use in the clinical care of TKR patients.

Establishment and validation of a prediction model for the probability of malignancy in solid solitary pulmonary nodules in northwest China.

BACKGROUND AND OBJECTIVES: To construct a prediction model of solitary pulmonary nodules (SPNs), to predict the possibility of malignant SPNs in patients aged 15-85 years in northwest China for clinical diagnostic and therapeutic decision-making. METHODS: The features of SPNs were assessed by multivariate logistic regression, followed by visualization using a nomogram. Hosmer lemeshow was applied to evaluate the fitting degree of the model. The area under the receiver operating characteristic (ROC) curve was identified to determine the discriminative ability of the model. RESULTS: Lobulation, spiculation, pleural-tag, carcinoembryonic antigen, neuron-specific enolase, and total serum protein were independent predictors of malignant pulmonary nodules (p < .05). Lobulation (100 points) scored the highest in the nomogram, and the Hosmer-Lemeshow goodness-of-fit statistic was 0.805 (p > .05). The area under curve (AUC) of the modeling and validation groups using logistic regression were 0.859 (95% CI, 0.805-0.903) and 0.823 (95% CI, 0.738-0.890), respectively. Moreover, the AUC of our model was higher than that of the Mayo model, VA model, and Peking University (AUC 0.823 vs. 0.655 vs. 0.603 vs. 0.521). CONCLUSION: Our prediction model is more suitable for predicting the possibility of malignant SPNs in northwest China, and can be calculated using a nomogram to determine further treatments.

Stelleranoids A-M, guaiane-type sesquiterpenoids based on [5,7] bicyclic system from Stellera chamaejasme and their cytotoxic activity.

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A-M (1-13), along with six known analogues (14-20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC50 of 9.8, 17.4 and 7.3 µM, respectively; compounds 3 and 8 displayed moderate cytotoxic effect against MKN-45 and Du145 cell lines with IC50 ranged from 14.5 to 18.8 µM, comparable to those of the positive control. As determined by fluorescent microscopy and flow cytometry in Du145 cell line, compound 14 could promote cell apoptosis and cause cell cycle arrest at the G0/G1 phase, leading to the inhibition of cell proliferation. Further Western blot analysis revealed that this inhibitory effect was accompanied by upregulating pro-apoptosis proteins cleaved-PARP, cleaved-Caspase-9 and tumor suppressor protein p53 while downregulating anti-apoptotic protein Bcl-2 in 14-treated Du145 cells.

Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A-L (1-12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B-C (2-3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D-F (4-6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model.

Young Children's Mathematical Learning From Intelligent Characters.

Children's math learning (N = 217; Mage  = 4.87 years; 63% European American, 96% college-educated families) from an intelligent character game was examined via social meaningfulness (parasocial relationships [PSRs]) and social contingency (parasocial interactions, e.g., math talk). In three studies (data collected in the DC area: 12/2015-10/2017), children's parasocial relationships and math talk with the intelligent character predicted quicker, more accurate math responses during virtual game play. Children performed better on a math transfer task with physical objects when exposed to an embodied character (Study 2), and when the character used socially contingent replies, which was mediated by math talk (Study 3). Results suggest that children's parasocial relationships and parasocial interactions with intelligent characters provide new frontiers for 21st century learning.

Lignocellulosic biomass-derived functional nanocellulose for food-related applications: A review.

In recent years, nanocellulose (NC) has gained significant attention due to its remarkable properties, such as adjustable surface chemistry, extraordinary biological properties, low toxicity and low density. This review summarizes the preparation of NC derived from lignocellulosic biomass (LCB), including cellulose nanofibrils (CNF), cellulose nanocrystals (CNC), and lignin-containing cellulose nanofibrils (LCNF). It focuses on examining the impact of non-cellulosic components such as lignin and hemicellulose on the functionality of NC. Additionally, various surface modification strategies of NC were discussed, including esterification, etherification and silylation. The review also emphasizes the progress of NC application in areas such as Pickering emulsions, food packaging materials, food additives, and hydrogels. Finally, the prospects for producing NC from LCB and its application in food-related fields are examined. This work aims to demonstrate the effective benefits of preparing NC from lignocellulosic biomass and its potential application in the food industry.

Multifunctional composite film of curcumin Pickering emulsion stabilized by lignocellulose nanofibrils isolated from bamboo shoot shells for monitoring shrimp freshness.

Concerns about food safety and environmental impact from chemical surfactants have prompted interest in natural lignocellulosic materials as alternatives. In this study, we combined hydrated deep eutectic solvent (DES) pretreatment with ultrasound treatment to prepare lignocellulosic nanofibrils (LCNF) from bamboo shoot shells with appropriate surface properties for stabilizing Pickering emulsions. The pretreatment intensity effectively modulated the surface characteristics of LCNF, achieving desirable wettability through lignin retention and in-situ esterification. The resulting LCNF/curcumin Pickering emulsion (CPE) demonstrated curcumin protection and pH-responsive color changes, while the ensuing CPE/PVA composite film exhibited ultraviolet shielding, mechanical strength, oxygen barrier, and antioxidant properties. Furthermore, the CPE/PVA film showed promise as a real-time indicator for monitoring shrimp freshness, maintaining sensitivity to spoilage even after six months of storage. These findings advance the advancement of green LCNF technologies, providing eco-friendly solutions for valorizing bamboo shoot shells and enhancing the application of LCNF in Pickering emulsions.

Case report: A novel variant (H49N) in Myelin Protein Zero gene is responsible for a patient with Charcot-Marie-Tooth disease.

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

Modulation of action potential trains in rabbit saphenous nerve unmyelinated fibers.

Usually, the main axon is assumed to faithfully conduct action potentials (APs). Recent data have indicated that neural processing can occur along the axonal path. However, the patterns and mechanisms of temporal coding are not clear. In the present study, single fiber recording was used to analyze activity-dependent modulation of AP trains in the main axons of C fibers in the rabbit saphenous nerve. Trains of 5 superthreshold electrical pulses at interstimulus intervals of 20 or 50 ms were applied to the nerve trunk for 200 s. The interspike intervals (ISIs) for these trains were compared to the input interstimulus intervals. Three basic types of C fibers were observed in response to repeated stimuli: first, the ISI between the first and second AP (ISI1-2) of type 1 was longer than the interstimulus interval; second, the ISI1-2 of type 2 showed wavelike fluctuations around the interstimulus interval, and third, the ISI1-2 of type 3 exhibited shorter intervals for a long period. Furthermore, both 4-aminopyridine-sensitive potassium and hyperpolarization-activated cation currents were involved in the modulation of ISI1-2 of train pulses. These data provide new evidence that multiple modes of neural conduction can occur along the main axons of C fibers.

Dopamine inhibits high-frequency stimulation-induced long-term potentiation of intrinsic excitability in CA1 hippocampal pyramidal neurons.

The efficiency of neural circuits is modified by changes not only in synaptic strength, but also in intrinsic excitability of neurons. In CA1 hippocampal pyramidal neurons, bidirectional changes in the intrinsic excitability are often presented after induction of synaptic long-term potentiation or depression. This plasticity of intrinsic excitability has been identified as a cellular correlate of learning. Besides, behavioral learning often involves action of reinforcement or rewarding mediated by dopamine (DA). Here, we examined how DA influences the intrinsic plasticity of CA1 hippocampal pyramidal neurons when high-frequency stimulation (HFS) was applied to Schaffer collaterals. The results showed that DA inhibits the decrease in rheobase and increase in mean firing rate of pyramidal neurons induced by HFS, and that this inhibition was abolished by the D1-like receptor antagonist SCH23390 but not by the D2-like receptor antagonist sulpiride. The results suggest that DA inhibits the potentiation of excitability induced by presynaptic HFS, and that this inhibition depends on the activation of D1-like receptors.

[High-frequency stimulation on cell soma induces potentiation of intrinsic excitability in VTA dopaminergic neurons].

Ventral tegmental area (VTA) is an important relay station of signal transmission in the reward system. The plasticity of VTA dopaminergic neurons directly influences actions of other regions of the reward system. Studies concerning the plasticity of VTA dopaminergic neurons focus mainly on synaptic plasticity, while much less attention has been given to the plasticity of intrinsic excitability of the neurons. The aim of the present study was to investigate the effect of high-frequency stimulation (HFS) on the plasticity of excitability of VTA neuron. Whole-cell patch-clamping was performed on VTA dopaminergic neurons in midbrain slices bathed with PTX, AP-5 and CNQX, and HFS was introduced to cell soma. The result showed that, after HFS induction the pharmacologically isolated neurons showed increased input resistance and firing frequency, as well as decreased rheobase. Meanwhile, the steady-state whole-cell current decreased, and the hyperpolarization-activated current (I(h)) decreased. These results suggest that HFS on soma induces a long-term potentiation of excitability in VTA dopaminergic neurons, and the underlying mechanism involves the changes of membrane current.

Enhancing saccharification of bamboo shoot shells by rapid one-pot pretreatment of hydrated deep eutectic solvent.

In this work, a rapid one-pot hydrated deep eutectic solvent (DES) pretreatment was proposed to facilitate the conversion of carbohydrates from lignocellulosic biomass to monosaccharides. Specifically, the pure and hydrated DES based on benzyl triethylammonium chloride (BTEAC), formic acid (FA) and water was used to pretreat bamboo shoot shells (BSS) by microwave heating. The pretreated solid residues were enzymatically saccharified to produce fermentable sugars, and the hydrolyzed carbohydrates and lignin remained in the hydrolyzate. The results showed that the yield of monosaccharides from the hydrated DES hydrolyzate (193.7-228.4 g/kg) was significantly higher than that (45.9-66.1 g/kg) of pure DES. The 30% hydrated DES pretreatment achieved the best glucose yield (89.03%) and a total monosaccharides yield of 555.4 g/kg, which corresponded to a conversion ratio of carbohydrates to monosaccharides of 87.0%. The proposed process is a robust method for the efficiently convert carbohydrates from BSS into monosaccharides.

Molecular data and ecological niche modelling reveal a highly dynamic evolutionary history of the East Asian Tertiary relict Cercidiphyllum (Cercidiphyllaceae).

East Asia's temperate deciduous forests served as sanctuary for Tertiary relict trees, but their ages and response to past climate change remain largely unknown. To address this issue, we elucidated the evolutionary and population demographic history of Cercdiphyllum, comprising species in China/Japan (Cercdiphyllum japonicum) and central Japan (Cercdiphyllum magnificum). Fifty-three populations were genotyped using chloroplast and ribosomal DNA sequences and microsatellite loci to assess molecular structure and diversity in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modelling. Late Tertiary climate cooling was reflected in a relatively recent speciation event, dated at the Mio-/Pliocene boundary. During glacials, the warm-temperate C. japonicum experienced massive habitat losses in some areas (north-central China/north Japan) but increases in others (southwest/-east China, East China Sea landbridge, south Japan). In China, the Sichuan Basin and/or the middle-Yangtze were source areas of postglacial northward recolonization; in Japan, this may have been facilitated through introgressive hybridization with the cool-temperate C. magnificum. Our findings challenge the notion of relative evolutionary and demographic stability of Tertiary relict trees, and may serve as a guideline for assessing the impact of Neogene climate change on the evolution and distribution of East Asian temperate plants.

Climate oscillation during the Quaternary associated with landscape heterogeneity promoted allopatric lineage divergence of a temperate tree Kalopanax septemlobus (Araliaceae) in East Asia.

We investigated the biogeographic history of Kalopanax septemlobus, one of the most widespread temperate tree species in East Asia, using a combined phylogeographic and palaeodistribution modelling approach. Range-wide genetic differentiation at nuclear microsatellites (G'(ST) = 0.709; 2205 samples genotyped at five loci) and chloroplast DNA (G(ST) = 0.697; 576 samples sequenced for 2055 bp at three fragments) was high. A major phylogeographic break in Central China corresponded with those of other temperate species and the spatial delineation of the two temperate forest subkingdoms of East Asia, consistent with the forests having been isolated within both East and West China for multiple glacial-interglacial cycles. Evidence for multiple glacial refugia was found in most of its current range in China, South Japan and the southernmost part of the Korean Peninsula. In contrast, lineage admixture and absence of private alleles and haplotypes in Hokkaido and the northern Korean Peninsula support a postglacial origin of northernmost populations. Although palaeodistribution modelling predicted suitable climate across a land-bridge extending from South Japan to East China during the Last Glacial Maximum, the genetic differentiation of regional populations indicated a limited role of the exposed sea floor as a dispersal corridor at that time. Overall, this study provides evidence that differential impacts of Quaternary climate oscillation associated with landscape heterogeneity have shaped the genetic structure of a wide-ranging temperate tree in East Asia.

[Regulation of pyloric rhythm by I(A) and I(h) in crayfish stomatogastric ganglion].

The stomatogastric ganglion (STG) of shellfish includes 30 neurons and produces pyloric rhythms. It is the common model to study central pattern generator (CPG). Regulation of pyloric rhythms not only is related to the property of single neurons in STG but also depends on the connections and property of the whole neuronal network. It has been found that transient potassium current (I(A)) and hyperpolarization-activated cation current (I(h)) exist in certain types of neurons of STG. However, roles played by these two currents in maintaining and regulating the pyloric rhythms are unknown. In the present study, in vitro electrophysiological recordings were performed on crayfish STG to examine the role played by I(A) and I(h) in regulation of pyloric rhythm. 4AP (2 mmol/L), a specific inhibitor of I(A), caused a decrease in pyloric cycle (P < 0.01), an increase in PD (pyloric dilator) ratio, a decrease in PY (pyloric) ratio (P < 0.01) and delay of phases of LP and PY firing. ZD7288 (100 µmol/L), a specific inhibitor of I(h), caused a decrease in pyloric cycle (P < 0.01), an increase in PD ratio (P < 0.01), an increase in LP (lateral pyloric) ratio (P < 0.01), a decrease in PY ratio (P < 0.01) and delay of phases of LP and PY firing. These results indicate that I(A) and I(h) play important roles in regulating pyloric rhythms in crayfish STG.

Microscopic Colitis Is Associated With a Reduced Risk of Colorectal Adenoma and Cancer: A Meta-Analysis.

BACKGROUND: The study sought to conduct a systematic review and meta-analysis of the risk of colorectal adenoma or cancer in patients with microscopic colitis (MC). METHODS: A comprehensive literature search of PubMed and EMBASE databases was performed. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to examine the effect of MC on the risk of colorectal adenoma or cancer. RESULTS: Twelve studies reporting the outcomes of 50 795 patients with MC were eligible for this meta-analysis. MC was negatively associated with the risk of colorectal adenoma compared with participants without MC (RR, 0.44; 95% CI, 0.33-0.58; P < .001; I2 = 87.3%). Also, the rate of colorectal cancer was lower in the patients with MC compared with the general population (RR, 0.62; 95% CI, 0.43-0.89; P = .01; I2 = 91.6%). In addition, sensitivity and subgroup analyses indicated that the results were robust. CONCLUSIONS: The present systematic review indicated that patients with MC may be associated with a lower risk of colorectal adenoma or cancer. The clinical data support the current professional society guideline. A surveillance colonoscopy program is not recommended as standard for patients with MC.

Patients with microscopic colitis (MC) are less likely to have colon adenomas or cancer compared with those without MC, supporting the recommendation of the professional society to the effect that patients with MC do not require colonoscopic surveillance.

Cesarean section is not associated with increased risk of celiac disease in the offspring: a meta-analysis.

OBJECTIVE: Epidemiologic findings are inconsistent concerning the association between cesarean section (C-section) and celiac disease in offspring. METHODS: We performed a systematic literature search of PubMed and Embase databases until July 2021. A meta-analysis was performed for each outcome in which a summary odds ratio (OR) was calculated while taking heterogeneity into account. RESULTS: A total of 11 observational were identified for the literature review. We found that C-section was not associated with an increase in the risk of CD (OR = 1.03, 95% CI, 0.95-1.12; p = .501). In subgroup analyses, the association remained insignificant for both infants born after elective C-section (OR 1.05; 0.95-1.16; p = .329) and emergency C-section (OR 1.06; 1-1.13; p = .051). CONCLUSIONS: Our results indicate that C-section is not associated with CD in offspring.