GABA promotes interstitial fluid clearance in an AQP4-dependent manner by activating the GABAA R.

The glymphatic system is a newly discovered perivascular network where cerebrospinal fluid mixes with interstitial fluid, facilitating clearance of protein solutes and metabolic waste from the parenchyma. The process is strictly dependent on water channel aquaporin-4 (AQP4) expressed on the perivascular astrocytic end-feet. Various factors, such as noradrenaline levels related to the arousal state, influence clearance efficiency, highlighting the possibility that other neurotransmitters additionally modulate this process. To date, the specific role of γ-aminobutyric acid (GABA) in the glymphatic system remains unknown. We used C57BL/6J mice to observe the regulatory effect of GABA on glymphatic pathway by administering a cerebrospinal fluid tracer containing GABA or its GABAA receptor (GABAA R) antagonist through cisterna magna injection. Then, we employed an AQP4 knockout mouse model to explore the regulatory effects of GABA on glymphatic drainage and further study whether transcranial magnetic stimulation-continuous theta burst stimulation (cTBS) could regulate the glymphatic pathway through the GABA system. Our data showed that GABA promotes glymphatic clearance in an AQP4-dependent manner by activating the GABAA R. Furthermore, cTBS was found to modulate the glymphatic pathway by activating the GABA system. Accordingly, we propose that regulating the GABA system by cTBS could modulate glymphatic clearance and provide new insight for clinical prevention and treatment of abnormal protein deposition-related diseases.

Electron Presolvation in Tetrahydrofuran-Incorporated Supramolecular Sodium Entities.

Alkali metal atoms can repopulate their valence electrons toward solvation due to impact from solvents or microsurroundings and provide the remaining alkali metal cations for coordinating with a variety of specific solvents, forming various electron-expanded complexes or solvated ionic pairs with special interactions. Such special solute-solvent interactions not only affect their electronic structures but also enable the formation of entirely new species. Taking Na(THF)n (n = 1-6, THF = tetrahydrofuran) and Na2@THF complexes as typical representatives, density functional theory calculations are carried out to explore the solvation of a sodium atom and its dimer in THF and characterize their complexes as solvent-incorporated supramolecular entities and particularly valence electron presolvation due to their interaction with solvent THF. Electron presolvation is caused by the Pauli repulsion between THF containing a coordinating O atom with a lone pair of electrons and the alkali metal Na or Na2 containing valence electrons, and THF coordination to them forces their valence electrons to redistribute, which can be easily realized in such solvents. Compared with strongly bound valance electrons of alkali metal atoms, THF coordination enables Na or Na2 electrons to exhibit much more active states (i.e., the presolvated states) featuring small vertical detachment energies of electrons and distorted diffuse distributions in the frames of the generally structured metal cation complexes, acting as the electron-expanded chemical entities. Furthermore, the degree of electron diffusion and the polarity of the Na-Na bond are proportional to the coordination number (n) and the coordination number difference (Δn) between two Na centers in Na2@THF. The unique properties of such entities are also discussed. This work offers a theoretical support to the supramolecular entities formed by alkali-metal atoms or their dimers with ligands containing O or N and uncovers the unique electron presolvation phenomena and also enriches our understanding of the novel metal atom complexes.

Exercise combined with heat treatment improves insulin resistance in diet-induced obese rats.

Insulin resistance is a risk factor for various cardiovascular diseases, which seriously threaten human health. Thus, finding a safe, effective and economical strategy to treat insulin resistance is urgently needed. This study aimed to investigate the effects of exercise combined with heat treatment on the insulin sensitivity in skeletal muscle of diet-induced obese (DIO) rats. Obese rats were induced by a 10-week high-fat diet and were randomly divided into normal temperature + control (NC), normal temperature + exercise (NE), heat treatment + control (HC) and heat treatment + exercise (HE) groups for 7 weeks of incremental load endurance exercise and heat treatment (exposure to a high-temperature environment room). At the end of the 7-week intervention, we measured fasting blood glucose, serum fasting insulin, serum leptin, serum adiponectin, protein expression of HSF1/HSP27 and JAK2/STAT3 pathway in soleus (primarily composed of slow-twitch fibres) and extensor digitorum longus (primarily composed of fast-twitch fibres) muscles. The results showed that exercise combined with heat treatment can effectively improve insulin resistance by regulating HSF1/HSP27 and JAK2/STAT3 pathways in the slow-twitch muscle of DIO rats. Importantly, exercise combined with heat treatment is more effective in improving insulin resistance in DIO rats than exercise or heat treatment alone. Low-moderate intensity exercise that stimulates slow-twitch muscle, combined with heat treatment is an effective strategy to treat insulin resistance.

Microglial exosomes facilitate α-synuclein transmission in Parkinson's disease.

Accumulation of neuronal α-synuclein is a prominent feature in Parkinson's disease. More recently, such abnormal protein aggregation has been reported to spread from cell to cell and exosomes are considered as important mediators. The focus of such research, however, has been primarily in neurons. Given the increasing recognition of the importance of non-cell autonomous-mediated neurotoxicity, it is critical to investigate the contribution of glia to α-synuclein aggregation and spread. Microglia are the primary phagocytes in the brain and have been well-documented as inducers of neuroinflammation. How and to what extent microglia and their exosomes impact α-synuclein pathology has not been well delineated. We report here that when treated with human α-synuclein preformed fibrils, exosomes containing α-synuclein released by microglia are fully capable of inducing protein aggregation in the recipient neurons. Additionally, when combined with microglial proinflammatory cytokines, these exosomes further increased protein aggregation in neurons. Inhibition of exosome synthesis in microglia reduced α-synuclein transmission. The in vivo significance of these exosomes was demonstrated by stereotaxic injection of exosomes isolated from α-synuclein preformed fibrils treated microglia into the mouse striatum. Phosphorylated α-synuclein was observed in multiple brain regions consistent with their neuronal connectivity. These animals also exhibited neurodegeneration in the nigrostriatal pathway in a time-dependent manner. Depleting microglia in vivo dramatically suppressed the transmission of α-synuclein after stereotaxic injection of preformed fibrils. Mechanistically, we report here that α-synuclein preformed fibrils impaired autophagy flux by upregulating PELI1, which in turn, resulted in degradation of LAMP2 in activated microglia. More importantly, by purifying microglia/macrophage derived exosomes in the CSF of Parkinson's disease patients, we confirmed the presence of α-synuclein oligomer in CD11b+ exosomes, which were able to induce α-synuclein aggregation in neurons, further supporting the translational aspect of this study. Taken together, our study supports the view that microglial exosomes contribute to the progression of α-synuclein pathology and therefore, they may serve as a promising therapeutic target for Parkinson's disease.

General Dual-Switched Dynamic Singlet Fission Channels in Solvents Governed Jointly by Chromophore Structural Dynamics and Solvent Impact: Singlet Prefission Energetics Analyses.

The singlet fission (SF) channels in many systems are controlled by the thermodynamic driving force (Switch-1) and kinetic barrier (Switch-2), both of which could be modulated by chromophore structure dynamics and solvent properties. Using ab initio molecular dynamics (AIMD), we here simulate how the structural dynamics and solvent jointly govern singlet prefission energetics, taking a covalent BODIPY dimer (di-BODIPY) in solvents as an example. We report a general dual-switched dynamic channel for intramolecular SF in solvents and suggest an effective AIMD sampling method to characterize the joint effect of chromophore structure dynamics and the solvent impact on SFs. Results reveal that the joint effect not only provides di-BODIPY more chances for meeting the SF thermodynamic requirement (Switch-1 ON) but also tunes the charge-transfer state toward removing the kinetic barrier (Switch-2 ON). Two factors jointly govern each switch in the dual-switched SF channel, and any one does not open the channel alone. We suggest a general principle for dynamically dual-switching the SF channel in solvents by utilizing the joint effect to tune the pre-SF energetics for photoexcitation and the opening of the subsequent channel. AIMD sampling is used for the first time to discover explicit solvent-solute interaction and dynamics information and thus their effect on excitation energetics. This work also shows the statistical information for an ensemble of SF chromophores in solvents, which can undergo different photoexcitations and possible SFs. The high agreement of the findings here with the experiments justifies our AIMD sampling-based pre-SF energetic prediction as a reliable way for exploring novel SF systems and their controllability.

Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice.

BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson's disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

In chronic hypoxia, glucose availability and hypoxic severity dictate the balance between HIF-1 and HIF-2 in astrocytes.

Astrocyte function is an important contributor to cellular viability during brain hypoxia and ischemia. Levels of the hypoxia-inducible transcription factors (HIFs) HIF-1 and HIF-2 are increased in hypoxic conditions and impact the neuroprotective properties of astrocytes. For example, HIF-2 induces levels of erythropoietin (EPO), a neuroprotectant, by astrocytes. In contrast, HIF-1 activity in astrocytes diminishes the viability of neurons in cocultures during hypoxia. Thus, HIF-1 and HIF-2 may have opposing effects on astrocytes. In this study, we explore the balance of HIF-1 and HIF-2 signaling in astrocytes during chronic (1-7 d) hypoxia while altering the degree of hypoxia and glucose availability. In addition, we investigate the effects of these conditions on neuron apoptosis. During exposure to chronic moderate hypoxia (2% O2) and plentiful glucose (10 mM), HIF-2 and EPO abundance increases from d 1 to 7. Similarly, pretreatment with moderate hypoxia markedly increases the abundance of HIF-2 and EPO when astrocytes are subsequently exposed to severe hypoxia (0.5% O2; 24 h) in 10 mM glucose, which inhibits neuron apoptosis in coculture. Although HIF-1 targets the expression increase during the 7 d in chronic moderate hypoxia (2% O2) and limited glucose (2 mM), further exposure to severe hypoxia (0.5% O2; 24 h) induces a decrease of most HIF-1 targets in astrocytes. Notably, in astrocyte exposure to 2% O2 prior to 0.5% O2, the expression of iNOS, an HIF-1-regulated protein, keeps increasing when glucose is limited, whereas EPO and VEGF abundance is suppressed, inducing increased apoptosis of neurons in coculture under limited glucose (2 mM). Thus, both hypoxic severity and glucose abundance regulate the balance of HIF-1 and HIF-2 activity in astrocytes, leading to diverse effects on neurons. These results could have important implications on the adaptive or pathologic role of astrocytes during chronic hypoxia and ischemia.-Guo, M., Ma, X., Feng, Y., Han, S., Dong, Q., Cui, M., Zhao, Y. In chronic hypoxia, glucose availability and hypoxic severity dictate the balance between HIF-1 and HIF-2 in astrocytes.

Inadequate dietary energy intake associates with higher prevalence of metabolic syndrome in different groups of hemodialysis patients: a clinical observational study in multiple dialysis centers.

BACKGROUND: Metabolic syndrome (MetS) has been established as a risk for cardiovascular diseases and mortality in hemodialysis patients. Energy intake (EI) is an important nutritional therapy for preventing MetS. We examined the association of self-reported dietary EI with metabolic abnormalities and MetS among hemodialysis patients. METHODS: A cross-sectional study design was carried out from September 2013 to April 2017 in seven hemodialysis centers. Data were collected from 228 hemodialysis patients with acceptable EI report, 20 years old and above, underwent three hemodialysis sessions a week for at least past 3 months. Dietary EI was evaluated by a three-day dietary record, and confirmed by 24-h dietary recall. Body compositions were measured by bioelectrical impedance analysis. Biochemical data were analyzed using standard laboratory tests. The cut-off values of daily EI were 30 kcal/kg, and 35 kcal/kg for age ≥ 60 years and < 60 years, respectively. MetS was defined by the American Association of Clinical Endocrinologists (AACE-MetS), and Harmonizing Metabolic Syndrome (HMetS). Logistic regression models were utilized for examining the association between EI and MetS. Age, gender, physical activity, hemodialysis vintage, Charlson comorbidity index, high sensitive C-reactive protein, and interdialytic weight gains were adjusted in the multivariate analysis. RESULTS: The prevalence of inadequate EI, AACE-MetS, and HMetS were 60.5%, 63.2%, and 53.9%, respectively. Inadequate EI was related to higher proportion of metabolic abnormalities and MetS (p <  0.05). Results of the multivariate analysis shows that inadequate EI was significantly linked with higher prevalence of impaired fasting glucose (OR = 2.42, p <  0.01), overweight/obese (OR = 6.70, p <  0.001), elevated waist circumference (OR = 8.17, p <  0.001), AACE-MetS (OR = 2.26, p <  0.01), and HMetS (OR = 3.52, p <  0.01). In subgroup anslysis, inadequate EI strongly associated with AACE-MetS in groups of non-hypertension (OR = 4.09, p = 0.004), and non-cardiovascular diseases (OR = 2.59, p = 0.012), and with HMetS in all sub-groups of hypertension (OR = 2.59~ 5.33, p <  0.05), diabetic group (OR = 8.33, p = 0.003), and non-cardiovascular diseases (OR = 3.79, p <  0.001). CONCLUSIONS: Inadequate EI and MetS prevalence was high. Energy intake strongly determined MetS in different groups of hemodialysis patients.

Liver X Receptor α Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn.

BACKGROUND: Liver X receptors, including α and ß isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown. METHODS: A spared nerve injury model was established in adult male rats and mice. Von Frey tests were performed to evaluate the neuropathic pain behavior; Western blot and immunohistochemistry were performed to understand the underlying mechanisms. RESULTS: Intrathecal injection of a specific liver X receptor agonist T0901317 or GW3965 could either prevent the development of mechanical allodynia or alleviate the established mechanical allodynia, both in rats and wild-type mice. GW3965 could inhibit the activation of glial cells and the expression of tumor necrosis factor-α (mean ± SD: 196 ± 48 vs. 119 ± 57; n = 6; P < 0.01) and interleukin 1ß (mean ± SD: 215 ± 69 vs. 158 ± 74; n = 6; P < 0.01) and increase the expression of interleukin 10 in the spinal dorsal horn. All of the above effects of GW3965 could be abolished by liver X receptor α mutation. Moreover, more glial cells were activated, and more interleukin 1ß was released in the spinal dorsal horn in liver X receptor α knockout mice than in wild-type mice after spared nerve injury. Aminoglutethimide, a neurosteroid synthesis inhibitor, blocked the inhibitory effect of T0901317 on mechanical allodynia, on the activation of glial cells, and on the expression of cytokines. CONCLUSIONS: Activation of liver X receptor α inhibits mechanical allodynia by inhibiting the activation of glial cells and rebalancing cytokines in the spinal dorsal horn via neurosteroids.

Diradicalized biphenyl derivative carbon-based material molecules: exploring the tuning effects on magnetic couplings.

While the conductance behavior of carbon-based couplers has been successfully investigated, insight into the magnetic properties of such carbon-based molecule coupled diradical systems is still scarce, and especially the structural effect of such couplers on the magnetic properties is poorly understood. The present work reports three different interference effects on the magnetic properties of carbon-based molecule coupled nitroxide diradicals: twisting, sideways group, and position effects. DFT calculations reveal that (i) torsion does not change their broken-symmetry singlet ground state and antiferromagnetic coupling, but decreases their magnetism; (ii) different linkages of two radical moieties result in different ground states and thus different magnetisms, depending on a combination of meta-sites and para-sites; (iii) the antiferromagnetic coupling with a broken-symmetry singlet ground state is not changed by adding sideways groups, but the coupling magnitude can be tuned by modifying the side-bridge. Discussions on geometries, magnetic properties, SOMO-SOMO splittings, and spin density distributions are made to clarify relevant magnetic behaviors. Clearly, the findings concerning the regulation of the diradicalized material molecules through modifying the carbon-based bridges provide a comprehensive understanding of the magnetism of such carbon-based diradicals and new prospects for the design of building blocks of magnetic functional molecular materials.

EXPRESS: Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats: Effect on loss of peripheral nerve fibers and imbalance of cytokines in the spinal dorsal horn.

BACKGROUND: Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. RESULTS: We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve. Moreover, in the spinal dorsal horn, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the protein expression of p-p65 as well as tumor necrosis factor a was increased, whereas the protein expression of IL-10 was decreased following vincristine treatment. Furthermore, intraperitoneal injection of methylcobalamin could dose dependently attenuate vincristine-induced mechanical allodynia and thermal hyperalgesia, which was associated with intraepidermal nerve fibers rescue, and atypical mitochondria prevalence decrease in the sciatic nerve. Moreover, methylcobalamin inhibited the activation of NADPH oxidase and the downstream NF-kB pathway. Production of tumor necrosis factor a was also decreased and production of IL-10 was increased in the spinal dorsal horn following methylcobalamin treatment. Intrathecal injection of Phorbol-12-Myristate-13-Acetate, a NADPH oxidase activator, could completely block the analgesic effect of methylcobalamin. CONCLUSIONS: Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-kB pathway, resulting in the rebalancing of proinflammatory and anti-inflammatory cytokines in the spinal dorsal horn might also be involved. These findings might provide potential target for preventing vincristine-induced neuropathic pain.

Computational insights into intriguing vibration-induced pulsing diradical character in perfluoropentacene and the perfluorination effect.

As an n-type organic semiconductor compound, perfluoropentacene has more widespread applications in organic electronics because of its higher electron mobility compared with its parent pentacene. Herein, we explore intriguing dynamic electronic properties of perfluoropentacene caused by structural vibrations using density functional theory calculations. Perfluoropentacene could exhibit diradical character because of the persistent vibrations, although it belongs to a closed-shell singlet molecule in its equilibrium configuration. Not all the vibration-induced structural changes can induce diradical character, but only those leading to a small singlet-triplet energy gap, especially the small HOMO-LUMO gap, as well as the short cross-linking C-C bonds and distorted carbon ring structures in polyacetylene chains make great contributions. Due to molecular vibrations, the diradical character of dynamic perfluoropentacene exhibits pulsing behavior. Compared with pentacene, its perfluorination can not only considerably stabilize two frontier molecular orbitals, but also reduce the HOMO-LUMO gap, thus leading to an increase of the number of vibrational modes which can make the diradical character appear. In particular, perfluorination makes 19 diradical vibrational modes appear in the low frequency region. These observations indicate that some low energy pulses can trigger perfluoropentacene molecular vibrations according to some low energy modes and thus the appearance of pulsing diradical character or molecular magnetism. Clearly, the observed novel characters of a molecule possessing hidden pulsing diradical character and tunable magnetism in this work would contribute to opening up promising areas for designing peculiar magnetic materials.

Exploring the Shared Genetic Architecture Between Obstructive Sleep Apnea and Body Mass Index.

Purpose: The reciprocal comorbidity of obstructive sleep apnea (OSA) and body mass index (BMI) has been observed, yet the shared genetic architecture between them remains unclear. This study aimed to explore the genetic overlaps between them. Methods: Summary statistics were acquired from the genome-wide association studies (GWASs) on OSA (Ncase = 41,704; Ncontrol = 335,573) and BMI (Noverall = 461,460). A comprehensive genome-wide cross-trait analysis was performed to quantify global and local genetic correlation, infer the bidirectional causal relationships, detect independent pleiotropic loci, and investigate potential comorbid genes. Results: A positive significant global genetic correlation between OSA and BMI was observed (r g = 0.52, P = 2.85e-122), which was supported by three local signal. The Mendelian randomization analysis confirmed bidirectional causal associations. In the meta-analysis of cross-traits GWAS, a total of 151 single-nucleotide polymorphisms were found to be pleiotropic between OSA and BMI. Additionally, we discovered that the genetic association between OSA and BMI is concentrated in 12 brain regions. Finally, a total 134 expression-tissue pairs were observed to have a significant impact on both OSA and BMI within the specified brain regions. Conclusion: Our comprehensive genome-wide cross-trait analysis indicates a shared genetic architecture between OSA and BMI, offering new perspectives on the possible mechanisms involved.

Cortical microinfarcts potentiate recurrent ischemic injury through NLRP3-dependent trained immunity.

Microinfarcts are common among the elderly and patients with microinfarcts are more vulnerable to another stroke. However, the impact of microinfarcts on recurrent stroke has yet to be fully understood. The purpose of this study was to explore the negative effects of microinfarcts on recurrent stroke. To achieve this, two-photon laser was used to induce microinfarcts, while photothrombotic stroke was induced on the opposite side. The results showed that microinfarcts led to trained immunity in microglia, which worsened the pro-inflammatory response and ischemic injury in the secondary photothrombotic stroke. Additionally, the study clarified the role of NLRP3 in microglial nuclei, indicating that it interacts with the MLL1 complex through NACHT domain and increases H3K4 methylation, which suggests that NLRP3 is critical in the formation of innate immune memory caused by microinfarcts. Furthermore, the knockout of NLRP3 in microglia alleviated the trained immunity and reduced the harmful effects of microinfarcts on recurrent stroke. This study emphasizes the detrimental effect of trained immunity on recurrent stroke and highlights the critical role of NLRP3 in mediating the formation of this memory, which may offer a potential therapeutic target for mitigating recurrent strokes.

Isolation, identification, and induced differentiation of satellite cells from skeletal muscle of adult tree shrews.

A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an "S"-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.

The relationship between family diet consumption, family environment, parent anxiety and nutrition status children during the COVID-19 pandemic: a longitudinal study.

Background: The COVID-19 pandemic has exacerbated the trends of childhood overweight, obesity, and malnutrition, as well as increased psychological stress and family conflicts among family members. It is important to explore the relationship between changes in the family environment during the COVID-19 on child nutrition. Objective: This study aims to analyze the nutritional status of Chinese children during the COVID-19 pandemic and its relationship with family diet, family environment, and parental anxiety, in order to provide evidence for further interventions in children's nutritional status. Method: This study included 7,645 primary and secondary school students and their parents from five schools in Chengdu, China. Chi-square tests were used to analyze the categorical variables of children's malnutrition, overweight, obesity, and parental anxiety. T-tests were used to assess changes in the continuous variable of family environment between two rounds of follow-up surveys. Multiple logistic regression analysis was employed to examine the impact of changes in family diet during the COVID-19 pandemic on children's nutritional status. Generalized estimating equations were used to analyze the effects of family environment and parental anxiety on childhood obesity. Result: The prevalence of malnutrition and obesity decreased from 11.64% and 11.60% in wave 1 to 4.96% and 10.50% in wave 2, and the rate of overweight increased from 13.11% in wave 1 to 13.73% in wave 2. Children whose families reduced consumption of staple foods during the COVID-19 were more likely to be frail, and families increased consumption of sugary drinks, take-out or meal delivery services, living in towns, family environmental barriers, and parental anxiety were risk factors for overweight obesity. Mother's education level in middle and high school and low age were protective factors for overweight obesity. Conclusion: The physical environment of the family, the emotions of family members, and children's perceptions of the family's soft environment can influence children's eating behaviors, children's nutritional intake, and malnutrition and obesity in children under public health emergencies, and family-based dietary interventions may be effective. Parents can increase consumption of healthy foods and improve the family environment, which improve their growth.

Variation of the stapes and its surrounding anatomical structures based on micro-computed tomography.

BACKGROUND: Stapedotomy is the most efficient treatment for otosclerosis. The anatomical structure of the operation area is complex, but it has a great impact on the postoperative effect. We measure the anatomical parameters of the stapes and its surrounding structures to provide an anatomical reference for stapes surgery in otosclerosis. MATERIALS AND METHODS: Fifteen adult cadaver heads (30 samples) were scanned using micro-CT. The stapes, facial nerve and external auditory canal were reconstructed by image processing. The stapes parameters and relationships between the stapes and surrounding structures were measured using a three-dimensional reconstruction model. RESULTS: The length, width and thickness of the stapes footplate were 2.93 ± 0.17 mm, 1.46 ± 0.08 mm and 0.30 ± 0.11 mm, respectively. The distance between the stapes footplate and long process of the incus was 3.79±0.39 mm. The angle of the incudostapedial joint was 88.29 ± 11.58°. The distance from the center of the stapes footplate to the facial canal was 1.60 ± 0.34 mm. In simulated stapes surgery, the minimum depth of the external auditory canal to be removed was 2.17 ± 0.91 mm, and no significant difference was found between the left and right sides and between men and women (P > 0.05). CONCLUSIONS: A three-dimensional model of the stapes bone and its surrounding anatomical structures was established based on Micro-CT imaging. Anatomical parameters of the stapes bone and its surrounding structures were measured using the model. In stapedotomy, the implanted piston diameter should be around 0.6mm, with a length of approximately 4.6mm. Care should be taken to protect the facial nerve canal during the surgery. These data provide reference for otologists.

Dosage selection and effect evaluation of sodium pentobarbital in tree shrew anesthesia.

To achieve surgical anesthesia in animal experimentation, it is important to select the appropriate anesthetic dose. However, few studies have investigated the reasonable anesthetic dose in tree shrew (Tupaia belangeri). The aim of the study was to review the literature to determine the most commonly used anesthetic dose in tree shrew and to calculate the reasonable equivalent dose between tree shrew and rat based on the body surface area conversion. Two groups of 10 adult tree shrews each were anesthetized with 1% sodium pentobarbital through intraperitoneal injection separately at doses of 62 mg/kg (equivalent dose) and 40 mg/kg (reported dose). Anesthetic depth and times were assessed in addition to vital signs. The results showed that the dosage was quite different across studies, ranging from 15 mg/kg to 80 mg/kg, with 40 mg/kg being the most frequently reported dose. However, the group of tree shrews anesthetized with the commonly reported dose were unable to meet the requirements of surgery. In contrast, the equivalent dose (62 mg/kg, intraperitoneal injection with sodium pentobarbital) calculated by body surface area conversion could achieve an anesthetic time of 44.28 ± 3.95 min with no serious or fatal effects. During anesthetic monitoring, we found that sodium pentobarbital had an inhibitory effect on the blood pressure, pulse rate, respiratory rate and rectal temperature in tree shrews, especially on the respiratory rate. Thus, our study indicated that the use of the equivalent dose of sodium pentobarbital was effective in anesthetizing tree shrews.

Effect of pretreatment strategies on halophyte Atriplex crassifolia to improve saccharification using thermostable cellulases.

Bioethanol is believed to be an influential revolutionary gift of biotechnology, owing to its elevating global demand and massive production. Pakistan is home to a rich diversity of halophytic flora, convertible into bounteous volumes of bioethanol. On the other hand, the accessibility to the cellulosic part of biomass is a major bottleneck in the successful application of biorefinery processes. The most common pre-treatment procedures existent include physicochemical and chemical approaches, which are not environmentally benign. To overcome these problems, biological pre-treatment has gained importance but the drawback is the low yield of the extracted monosaccharides. The current research was aimed at exploring the best pre-treatment method for the bioconversion of halophyte Atriplex crassifolia into saccharides using three thermostable cellulases. Atriplex crassifolia was subjected to acid, alkali and microwave pre-treatments, followed by compositional analysis of the pre-treated substrates. Maximum delignification i.e. 56.6% was observed in the substrate pre-treated using 3% HCl. Enzymatic saccharification using thermostable cellulases also validated the results where the highest saccharification yield i.e. 39.5% was observed for the sample pre-treated using same. Maximum enzymatic hydrolysis of 52.7% was obtained for 0.40 g of the pre-treated halophyte Atriplex crassifolia where Endo-1,4- ß -glucanase (300U), Exo-1,4- ß -glucanase (400U) and ß -1,4-glucosidase (1000U) were simultaneously added and incubated for 6 h at 75°C. The reducing sugar slurry obtained after optimization of saccharification was utilized as glucose in submerged fermentation for bioethanol production. The fermentation medium was inoculated with Saccharomyces cerevisiae, incubated at 30°C and 180 rpm for 96 h. Ethanol production was estimated using potassium dichromate method. Maximum production of bioethanol i.e. 16.33% was noted at 72 h. It can be concluded from the study that Atriplex crassifolia owing to its high cellulosic content after pre-treatment using dilute acid method, yields substantial amount of reducing sugars and high saccharification rates when subjected to enzymatic hydrolysis using thermostable cellulases, under optimized reaction conditions. Hence, the halophyte Atriplex crassifolia is a beneficial substrate that can be utilized to extract fermentable saccharides for bioethanol production.

Reciprocal effect between non-suicidal self-injury and depressive symptoms in adolescence.

Background: Non-suicidal self-injury (NSSI) is a common psychological and behavioral problem among adolescents. The COVID-19 pandemic has had a significant impact on people's mental health. To date, few studies have documented the temporal changes in adolescents' psychological status during the pandemic, as well as the impact of large-scale public health intervention strategies. This study contributes to the existing evidence on the subject. Methods: Participants were 6,023 adolescents aged 10 years and older, with data from two waves of longitudinal surveys, including data for a 7-month interval before and during the pandemic. A cross-lagged model was used to test the bidirectional relationship between NSSI and depressive symptoms in adolescents; logistic regression analysis was used to explore the predictors of NSSI implementation in adolescents with depressive symptoms. Results: In this study, 32.69% participants reported depressive symptoms at baseline and 34.27% at follow-up; 44.34% participants with depressive symptoms reported NSSI at baseline and 53.44% at follow-up. The duration of the online class, depressed affect, and somatic and related activity were the risk factors for NSSI; sleep duration and positive mood were the protective factors. The lag effect of depression symptoms on NSSI is significant, and so is NSSI on depressive symptoms. Conclusion: During the COVID-19 pandemic, adolescents' mental health has worsened, resulting in an increase in the prevalence of NSSI among those with depressive symptoms compared to pre-pandemic levels. Early screening for depression is crucial in preventing or decreasing NSSI in adolescents.