Exercise-induced changes in intramuscular total creatine concentration measured with 1H magnetic resonance spectroscopy: A pilot study.

Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well-controlled study, straight-leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6-lb load and 21.0% ± 1.3% with 12-lb load (p < 0.0001). Between two different days, baseline tCr, percentage decrease induced by exercise with a 6-lb and 12-lb load differed by 2.2% ± 2.3%, 11.7% ± 6.0% and 4.9% ± 3.2%, respectively. In conclusion, the proposed protocol of controlled exercise stimulation and MRS acquisition can reproducibly monitor tCr level and its exercise-induced change in skeletal muscles. The measured tCr level is sensitive to exercise intensity, so can be used to quantitatively assess muscle performance or fatigue.

Drug resistance in drug-resistant tuberculosis patients with and without diabetes mellitus: a comparative analysis.

BACKGROUND: This dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB). METHODS: A total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance. RESULTS: In both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB. CONCLUSION: Isoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

Effects of Exocellobiohydrolase CBHA on Fermentation of Tobacco Leaves.

The quality of tobacco is directly affected by macromolecular content, fermentation is an effective method to improve biochemical properties. In this study, we utilized CBHA (cellobiohydrolase A) glycosylase, which was expressed by Pichia pastoris, as an additive for fermentation. The contents of main chemical components of tobacco leaves after fermentation were determined, and the changes of microbial community structure and abundance in tobacco leaves during fermentation were analyzed. The relationship between chemical composition and changes in microbial composition was investigated, and the function of bacteria and fungi in fermentation was predicted to identify possible metabolic pathways. After 48 h of CBHA fermentation, the contents of starch, cellulose and total nitrogen in tobacco leaf decreased by 17.60%, 28.91% and 16.05%, respectively. The microbial community structure changed significantly, with Aspergillus abundance decreasing significantly, while Filobasidum, Cladosporium, Bullera, Komagataella, etc., increased in CBHA treated group. Soluble sugar was most affected by microbial community in tobacco leaves, which was negatively correlated with starch, cellulose and total nitrogen. During the fermentation process, the relative abundance of metabolism-related functional genes increased, and the expressions of cellulase and endopeptidase also increased. The results showed that the changes of bacterial community and dominant microbial community on tobacco leaves affected the content of chemical components in tobacco leaves, and adding CBHA for fermentation had a positive effect on improving the quality of tobacco leaves.

NOx precipitation and valorization driven by photocatalysis and adsorption over red soil.

Nitrogen oxides (NOx) emissions can cause air pollution that is harmful to human health, even producing serious ecological problems. Whether it is diluted in the air or not, the management and valorization of NOx from industrial emissions have been constrained by technology and finance. This study shows that red soil can be used as a photocatalyst to convert NOx into soil nitrate nitrogen (NO3--N) in the soil. The addition of zinc oxide (ZnO) and titanium dioxide (TiO2) onto the soil surface improves the photocatalytic precipitation efficiency of 1 ppm NO, approaching a removal efficiency of 77 % under ultraviolet (UV) light. The efficiency of red soil in precipitating NOx through adsorption exceeded that of photocatalysis at 100 ppm NOx (e.g. 16.02 % versus 7.70 % in 0.1-mm soil). Pot experiment reveals that the precipitated NO3--N promoted biomass of water spinach (Ipomoea aquatica Forsk). Additionally, adding ZnO or TiO2 also affects mineral nutrition. This demonstration of converting air pollutants into available nitrogen (N) for plant growth not only provides a new perspective on treatment and valorization for NOx but also sheds light on the transport of N in the air-soil-plant path.

Nursing-sensitive Indicators for Quality Improvement for Patients with Traumatic Brain Injury.

Context: Traumatic brain injury (TBI) can result in lifelong cognitive, emotional, and motor impairments. The emergency department is the first stop for diagnosing and treating patients with acute TBI, and the quality of nursing care can greatly influence the prognosis and progression of a patient's condition. Currently, standardized evaluation tools are lacking in the world for assessment of the quality of nursing care. Objective: The study intended to construct a nursing-sensitive indicator system for TBI patients, based on the scientific method of evidence-based nursing and the Delphi method, to provide a quantitative tool for emergency-nursing personnel to manage the quality of care for those patients. Design: Based on the Joanna Briggs Institute's evidence-based healthcare model, the research team performed a literature search and consulted reference guidelines, conducted two rounds of consultations with experts. sensitive indicators for quality of care, and constructed the sensitive indicator system. The team then conducted a retrospective study. Setting: The study took place in the department of emergency surgery at Shanxi Norman Bethune Hospital in Taiyuan, Shanxi, China. Participants: Participants were 56 patients with TBI who had been admitted to the emergency department between January 2022 and December 2022 and 44 patients with TBI who had been admitted to the emergency department between January 2023 and December 2023. Interventions: The research team assigned: (1) the 56 patients in the first group to the control group, who received routine nursing care and (2) the 44 patients in the second group to the intervention group, who received treatment using the sensitive indicator system for the quality of emergency care for TBI patients as well as routine care. Outcome Measures: In the verification study, the research team compared the group's rescue effects and satisfaction with emergency care. Results: In the first and second rounds of inquiries to experts, the research team distributed 25 questionnaires each time, with 25 valid questionnaires collected both times. The response rate for both rounds of inquiries was 100%. The expert authority coefficients for the first and second rounds of inquiries are 0.844 and 0.878, respectively. The sensitive indicator system's final construction included three primary indicators, seven secondary indicators, and 17 tertiary indicators. The AUC for the sensitive indicators was 0.8355882. The indicator system's use found that the intervention group had a shorter time to diagnosis (P < .001), emergency-department stay (P < .001), and emergency-department-to-surgery time (P < .001) compared to the control group. The intervention group also has a higher success rate for the emergency treatment (P = .014) and a higher nursing satisfaction with nurse-patient communications (P = .003), first-aid operations (P < .001), nursing attitudes (P < .001), and emergency environment (P < .001) compared to the control group. Conclusions: The process of constructing quality-sensitive indicators for the nursing care of TBI patients was scientific. The constructed quality-sensitive indicator system for the care of patients with TBI covers key factors that influence the quality of care. It's highly practical and has the ability to transform certain indicators, which can better guide the management of quality of care for TBI.

Optimized submerged batch fermentation for metabolic switching in Streptomyces yanglinensis 3-10 providing platform for reveromycin A and B biosynthesis, engineering, and production.

The cultivation system requires that the approach providing biomass for all types of metabolic analysis is of excellent quality and reliability. This study was conducted to enhance the efficiency and yield of antifungal substance (AFS) production in Streptomyces yanglinensis 3-10 by optimizing operation conditions of aeration, agitation, carbon source, and incubation time in a fermenter. Dissolved oxygen (DO) and pH were found to play significant roles in AFS production. The optimum pH for the production of AFS in S. yanglinensis 3-10 was found to be 6.5. As the AFS synthesis is generally thought to be an aerobic process, DO plays a significant role. The synthesis of bioactive compounds can vary depending on how DO affects growth rate. This study validates that the high growth rate and antifungal activity required a minimum DO concentration of approximately 20% saturation. The DO supply in a fermenter can be raised once agitation and aeration have been adjusted. Consequently, DO can stimulate the development of bacteria and enzyme production. A large shearing effect could result from the extreme agitation, harming the cell and deactivating its products. The highest inhibition zone diameter (IZD) was obtained with 3% starch, making starch a more efficient carbon source than glucose. Temperature is another important factor affecting AFS production. The needed fermentation time would increase and AFS production would be reduced by the too-low operating temperature. Furthermore, large-scale fermenters are challenging to manage at temperatures that are far below from room temperature. According to this research, 28°C is the ideal temperature for the fermentation of S. yanglinensis 3-10. The current study deals with the optimization of submerged batch fermentation involving the modification of operation conditions to effectively enhance the efficiency and yield of AFS production in S. yanglinensis 3-10.

Thrombospondin 4, a mediator and candidate indicator of pain.

Pain is the most common symptom for which patients seek medical attention. Existing treatments for pain control are largely ineffective due to the lack of an accurate way to objectively measure pain intensity and a poor understanding of the etiology of pain. Thrombospondin 4(TSP4), a member of the thrombospondin gene family, is expressed in neurons and astrocytes and induces pain by interacting with the calcium channel alpha-2-delta-1 subunit (Cavα2δ1). In the present study we show that TSP4 expression level correlates positively with pain intensity, suggesting that TSP4 could be a novel candidate of pain indicator. Using RNAi-lentivirus (RNAi-LV) to knock down TSP4 both in vivo and in vitro, together with electrophysiological experiments involving paired patch-clamp recordings of evoked action potentials and post-synaptic currents in cultured neurons, we found that TSP4 contributes to the development of bone cancer pain, neuropathic pain, and inflammatory pain. This effect is mediated by regulation of neuron excitability via inhibition of synapsin I (Syn I) and modulation of excitatory and inhibitory presynaptic transmission via regulation of vesicular glutamate transporter 2(Vglut2), vesicular GABA transporter (VGAT), and glutamate decarboxylase (GAD) expression. The present study provides a replicable, predictive, valid indicator of pain and demonstrated the underlying molecular and electrophysiological mechanisms by which TSP4 contributes to pain.

A novel and sensitive electrochemical aptasensor for sulfadimethoxine detection based on the triple helix/exonuclease I-assisted double-amplification strategy.

In this paper, a novel and sensitive electrochemical aptasensor for sulfadimethoxine (SDM) detection has been designed based on the triple helix structure/exonuclease I (Exo I)-assisted double signal amplification strategy. The aptamer probe (Apt) hybridizes with the signal transduction probe (STP) on the electrode to form a rigid double-stranded DNA (dsDNA) structure, so that the STP remains upright and methylene blue (MB) on the STP is far away from the electrode surface, resulting in a delicate current signal. In the presence of SDM, the SDM and Apt combine into a complex, leading to the transfer of the Apt and the exposure of the STP. Meanwhile, the added Exo I can digest the Apt to realize the cyclic amplification of SDM. After the addition of the signal probe (SP), a triple helix structure between the SP and STP is formed under acidic conditions, and MB on the STP and SP collide with the electrode surface to generate a strong electrochemical signal. The proposed aptasensor combines the features of the triple helix structure and Exo I to achieve double signal amplification for the sensitive detection of SDM with a wide linear range of 0.05-1000 ng mL-1 and a low detection limit of 0.02 ng mL-1. Furthermore, it has been successfully used to detect SDM in milk and lake water samples.

MHC-I in the hippocampus promotes comorbid depressive symptoms in bone cancer pain via the upregulation of microglial TREM2/DAP12 signaling.

Pain and depression comorbidity affects patients' physical and mental health, as well as quality of life. Comorbid depressive symptoms in cancer pain have a severe impact on the recognition and treatment of pain. Similarly, cancer pain patients with depression are inclined towards more despair and greater impairment. The mechanisms responsible for the comorbid depressive symptoms in bone cancer pain (BCP) have not been fully delineated. Here, it was reported that the implantation of carcinoma cells into the femoral cavity of mice led to the upregulation of major histocompatibility complex class I (MHC-I) in the hippocampus. This was associated with the activation of microglial signaling pathway mediated by the triggering receptor expressed on myeloid cells 2 protein (TREM2) and DNAX-activating protein of 12 kDa (DAP12). Pain and depression-like behaviors were reversed by the knockdown of hippocampal MHC-I via a lentiviral vector harboring ribonucleic acid interference (RNAi) sequence. Moreover, MHC-I knockdown exhibited a marked reduction in the expression of TREM2 and DAP12. These results suggested that hippocampal MHC-I was involved in BCP and depression comorbidity via upregulating the signals mediated by TREM2/DAP12 in microglia. The suppression of MHC-I could be a potential therapeutic target for BCP.

Upregulation of Calhm2 in the anterior cingulate cortex contributes to the maintenance of bilateral mechanical allodynia and comorbid anxiety symptoms in inflammatory pain conditions.

Peripheral inflammation-induced chronic pain tends to evoke concomitant anxiety disorders. It's common knowledge that the anterior cingulate cortex (ACC) plays a vital role in maintaining pain modulation and negative emotions. However, the potential mechanisms of chronic inflammation pain and pain-related anxiety remain elusive. Here, it was reported that injecting complete Freund's adjuvant (CFA) unilaterally resulted in bilateral mechanical allodynia and anxiety-like symptoms in mice via behavioral tests. In addition, CFA induced the bilateral upregulation and activation of calcium homeostasis modulator 2 (Calhm2) in ACC pyramidal neurons by quantitative analysis and double immunofluorescence staining. The knockdown of Calhm2 in the bilateral ACC by a lentiviral vector harboring ribonucleic acid (RNA) interference sequence reversed CFA-induced pain behaviors and neuronal sensitization. Furthermore, the modulating of ACC pyramidal neuronal activities via a designer receptor exclusively activated by designer drugs (DREADD)-hM4D(Gi) greatly changed Calhm2 expression, mechanical paw withdrawal thresholds (PWTs) and comorbid anxiety symptoms. Moreover, it was found that Calhm2 regulates inflammation pain promoting the upregulation of N-methyl-D-aspartic acid (NMDA) receptor 2B (NR2B) subunits. Calhm2 knockdown in ACC exhibited a significant decrease in NR2B expression. These results demonstrated that Calhm2 in ACC pyramidal neurons modulates chronic inflammation pain and pain-related anxiety symptoms, which provides a novel underlying mechanism for the development of inflammation pain.

PLPPR4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via mTOR signalling.

Phospholipid phosphatase related 4 (PLPPR4), a neuron-specific membrane protein located at the postsynaptic density of glutamatergic synapses, is a putative regulator of neuronal plasticity. However, PLPPR4 dysfunction has not been linked to genetic disorders. In this study, we report three unrelated patients with intellectual disability (ID) or autism spectrum disorder (ASD) who harbour a de novo heterozygous copy number loss of PLPPR4 in 1p21.2p21.3, a heterozygous nonsense mutation in PLPPR4 (NM_014839, c.4C > T, p.Gln2*) and a homozygous splice mutation in PLPPR4 (NM_014839: c.408 + 2 T > C), respectively. Bionano single-molecule optical mapping confirmed PLPPR4 deletion contains no additional pathogenic genes. Our results suggested that the loss of function of PLPPR4 is associated with neurodevelopmental disorders. To test the pathogenesis of PLPPR4, peripheral blood mononuclear cells obtained from the patient with heterozygous deletion of PLPPR4 were induced to specific iPSCs (CHWi001-A) and then differentiated into neurons. The neurons carrying the deletion of PLPPR4 displayed the reduced density of dendritic protrusions, shorter neurites and reduced axon length, suggesting the causal role of PLPPR4 in neurodevelopmental disorders. As the mTOR signalling pathway was essential for regulating the axon maturation and function, we found that mTOR signalling was inhibited with a higher level of p-AKT, p-mTOR and p-ERK1/2, decreased p-PI3K in PLPPR4-iPSCs neurons. Additionally, we found silencing PLPPR4 disturbed the mTOR signalling pathway. Our results suggested PLPPR4 modulates neurodevelopment by affecting the plasticity of neurons via the mTOR signalling pathway.

Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array.

BACKGROUND: With the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof. RESULTS: Using SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication. CONCLUSION: Improved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.

An electrochemical aptasensor for detection of streptomycin based on signal amplification assisted by functionalized gold nanoparticles and hybridization chain reaction.

A ratiometric electrochemical aptasensor based on gold nanoparticles (AuNPs) functionalization and hybridization chain reaction (HCR) assisted signal amplification has been for the first time designed for the detection of streptomycin (STR). The double-stranded DNA (dsDNA) formed by the hybridization of ferrocene (Fc)-labeled STR aptamer (Apt) and capture probe (CP) is first immobilized on the gold electrode (GE) surface via Au-S reaction. The specific binding of the target and Apt results in numerous Fc detachment from the sensing interface. Then, the remaining single-stranded CP is combined with AuNPs modified with initiator DNA (iDNA) by auxiliary DNA (aDNA). Among them, the iDNA triggers HCR between two hairpin probes (H1/H2), thus capturing a large number of methylene blue (MB) electrochemical probe, which generates a strong electrochemical signal of MB and a weak electrochemical signal of Fc. Signals are collected by square wave voltammetry (the potential window ranging from -0.5 V to 0.6 V, vs. Ag/AgCl ), and the oxidation peak currents at -0.200 V (MB) and 0.416 V (Fc) are recorded. The use of the ratiometric method has effectively improved the accuracy and reliability of the analysis. The successful application of AuNPs and HCR greatly improves the sensitivity of the sensor, and the detection limit is as low as 0.08 pM. It can sensitively determine STR in the range 0.1 pM to 10 nM. In addition, the designed aptasensor has been successfully applied to the detection of STR in milk and honey samples.

Neuroligins facilitate the development of bone cancer pain via regulating synaptic transmission: an experimental study.

BACKGROUND: The underlying mechanism of chronic pain involves the plasticity in synaptic receptors and neurotransmitters. This study aimed to investigate potential roles of Neuroligins (NLs) within the spinal dorsal horn of rats in a newly established Bone Cancer Pain (BCP) model. The objective was to explore the mechanism of neuroligin involved in the occurrence and development of bone cancer pain. METHODS: Using our rat BCP model, we assessed pain hypersensitivity over time. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to investigate NL expression, and NLs were overexpressed in the rat spinal cord using lentiviral vectors. Immunofluorescence staining and whole-cell patch-clamp recordings were deployed to investigate the role of NLs in the development of BCP. RESULTS: We observed reduced expression levels of NL1 and NL2, but not of NL3, within the rat spinal cord, which were found to be associated with and essential for the development of BCP in our model. Accordingly, NL1 or NL2 overexpression in the spinal cord alleviated mechanical hypersensitivity of rats. Electrophysiological experiments indicated that NL1 and NL2 are involved in BCP via regulating γ-aminobutyric acid-ergic interneuronal synapses and the activity of glutamatergic interneuronal synapses, respectively. CONCLUSIONS: Our observations unravel the role of NLs in cancer-related chronic pain and further suggest that inhibitory mechanisms are central features of BCP in the spinal dorsal horn. These results provide a new perspective and basis for subsequent studies elucidating the onset and progression of BCP.

Lithium storage performance and mechanism of nano-sized Ti2InC MAX phase.

Fine powders of MAX phases (a family of layered carbides/nitrides) have been showing great promise in energy storage applications. A feasible method of obtaining nano-sized MAX phase particles is critical to realizing the practical application of the vast MAX phase family in more technologically important fields. Herein, ball milling, a commercial and feasible method, is employed to prepare nano-sized Ti2InC, which delivers a high specific capacity of 590 mA h g-1 after 500 cycles and maintains 574.4 mA h g-1 after 600 cycles at 0.1 A g-1 when used as a lithium storage anode. Compared with other methods (e.g., partial etching), decreasing the size of Ti2InC particles by ball milling can preserve the exfoliated indium (In) atoms, which have great volumetric and gravimetric capacities. In situ XRD analysis indicates that the capacity of the nano-sized Ti2InC primarily comes from the lithiation of elemental In exfoliated from Ti2InC, and in particular, the exfoliated In atoms by ball milling can increase the initial capacity. The lithiation/delithiation cycle can effectively activate and even exfoliate the Ti2InC grains, which accounts for the increasing capacity upon cycling.

Differential epitranscriptome and proteome modulation in the brain of neonatal mice exposed to isoflurane or sevoflurane.

BACKGROUND: Repeated neonatal exposure to anesthetics may disturb neurodevelopment and cause neuropsychological disorders. The m6A modification participates in the gene regulation of neurodevelopment in mouse fetuses exposed to anesthetics. This study aims to explore the underlying molecular mechanisms of neurotoxicity after early-life anesthesia exposure. METHODS: Mice were exposed to isoflurane (1.5%) or sevoflurane (2.3%) for 2 h daily during postnatal days (PND) 7-9. Sociability, spatial working memory, and anxiety-like behavior were assessed on PND 30-35. Synaptogenesis, epitranscriptome m6A, and the proteome of brain regions were evaluated on PND 21. RESULTS: Both isoflurane and sevoflurane produced abnormal social behaviors at the juvenile age, with different sociality patterns in each group. Synaptogenesis in the hippocampal area CA3 was increased in the sevoflurane-exposed mice. Both anesthetics led to numerous persistent m6A-induced alterations in the brain, associated with critical metabolic, developmental, and immune functions. The proteins altered by isoflurane exposure were mainly associated with epilepsy, ataxia, and brain development. As for sevoflurane, the altered proteins were involved in social behavior. CONCLUSIONS: Social interaction, the modulation patterns of the m6A modification, and protein expression were altered in an isoflurane or sevoflurane-specific way. Possible molecular pathways involved in brain impairment were revealed, as well as the mechanism underlying behavioral deficits following repeated exposure to anesthetics in newborns.

Extracellular magnetic labeling of biomimetic hydrogel-induced human mesenchymal stem cell spheroids with ferumoxytol for MRI tracking.

Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.

Lightweight and flexible PAN@PPy/MXene films with outstanding electromagnetic interference shielding and Joule heating performance.

Lightweight and flexible multifunctional materials with excellent electromagnetic interference (EMI) shielding and Joule heating performances are highly demanded for smart and wearable electronics. In this work, polyacrylonitrile (PAN) nanofiber films are prepared by electrospinning and then coated with polypyrrole (PPy) via vapor deposition, yielding a continuous three-dimensional (3D) conductive network of PAN@PPy. Ti3C2Tx MXene nanosheets with high electrical conductivity are sprayed on the PAN@PPy film to enhance its EMI shielding performance. The as-prepared PAN@PPy/MXene films (55 µm thick) exhibit a high EMI shielding effectiveness (SE) of 32 dB, achieving an extraordinarily high normalized surface-specific SE (SSE/t) of up to 17 534.5 dB cm2 g-1 from 8.2 to 12.4 GHz; simultaneously, the temperatures of PAN@PPy/MXene films can be driven up to 170.5 °C at an input voltage of 4 V, and exhibit fast-response, stable, and long-term Joule heating performance. The high SSE/t and efficient Joule heating ability of the films bode potential applications in smart and wearable devices.

Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next-generation sequencing in a Chinese family with nonsyndromic hearing loss.

BACKGROUND: Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations. METHOD: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed for the 14-year-old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next-generation sequencing (TGS) of 127 existing hearing loss-related genes in a 14-year-old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed. RESULTS: Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein. CONCLUSIONS: We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.

Enhanced inflammation and suppressed adaptive immunity in COVID-19 with prolonged RNA shedding.

Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.