Clinical analysis of sirolimus therapy in children with refractory nephrotic syndrome.

To investigate the clinical efficacy of sirolimus in treating children with refractory nephrotic syndrome, the clinical data for 22 children from the Children's Hospital of Hebei Province were analyzed retrospectively. There were 16 boys and six girls, and the treatment period was from September 2015 to April 2021. There were two patients with steroid-dependent nephrotic syndrome (SDNS), six patients with frequently relapsing nephrotic syndrome (FRNS), and 14 patients with steroid-resistant nephrotic syndrome (SRNS). All patients were defined as having refractory nephrotic syndrome. There were 12 patients (including nine SRNS patients and three FRNS patients) with minimal change disease (MCD), three patients (three SRNS patients) with focal segmental glomerular sclerosis (FSGS), one FRNS patient with mesangial proliferative glomerulonephritis (MsPGN), and six patients without a kidney biopsy. Compared with levels before sirolimus treatment, 24-hour urine protein (24-h UP), low-density lipoprotein cholesterol (LDL-C), urea (Ur) and serum creatinine (SCr) levels were significantly lower (all p < 0.05). Moreover, albumin (Alb) was significantly increased (p < 0.05), and there were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), immunoglobulin A (IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM) (all p > 0.05) at the first follow-up. Sirolimus is effective as the first treatment of some children with refractory nephrotic syndrome, but its long-term efficacy and adverse reactions still require follow-up.

Heteroatom doped graphitic carbon nanotubes as freestanding anodes for advanced potassium-ion batteries.

Owing to its higher earth element reserve and similar chemical properties to lithium, potassium ion batteries (PIBs) have been regarded as a potential alternative to lithium-ion batteries. And considering the relatively larger ionic radius of potassium, available electrode materials need to be equipped with enough space for volume expansion during charge-discharge cycles, thus graphitic carbon nanomaterials with adjustable layer spacing gradually come into researcher's version. Here with copper nanowires serving as growth template and organic polyvinyl pyrrolidone (PVP) providing carbon source, freestanding and ultra-light graphitic carbon nanotube (GCNT) aerogels were simply assembled and annealed, which were directly used as anodes of PIBs. Annealing parameters (temperature and atmosphere) were adapted to regulate the lattice order and interlayer spacing of GCNTs, and N, O heteroatoms derived from PVP were directly doped into the carbon lattice during thermal annealing, to optimize and enhance the cycle capacity and rate performance of GCNT anodes. The electrochemical potassium storage mechanism of GCNTs was also quantitatively analyzed. Most of the potassium ions are reversibly stored by squeezing into and escaping from the carbon lattice, and simultaneously oxygen-containing functional groups with different chemical states also offer active redox sites and dedicate partial capacity. Therefore, our assembled GCNTs with large lumen are expected to sandwich-like load with active substances efficiently, further constructing next-generation PIBs with excellent performance.

Preparation of amphiphilic poly(divinylbenzene-co-N-vinylpyrrolidone)-functionalized polydopamine magnetic nanoadsorbents for enrichment of synthetic cannabinoids in wastewater.

Concerns have been raised about synthetic cannabinoids (SCs), which are among the most often trafficked and used illegal substances. An analytical method that holds promise for determining illicit drug use in the general population is wastewater-based epidemiology (WBE). Unfortunately, the concentration of SCs in wastewater is often extremely low on account of their hydrophobic nature, thus presenting a significant obstacle to the accurate detection and quantification of SCs using WBE. In this study, we present novel magnetic nanomaterials as amphiphilic adsorbents for pretreatment of wastewater using magnetic solid phase extraction (MSPE). Polydopamine-modified Fe3O4 nanoparticles were used as the magnetic core and further functionalized with poly(divinylbenzene-N-vinylpyrrolidone). Coupled with UHPLC-MS/MS analysis, an analytical method to simultaneously detect nine SCs at trace-levels in wastewater was developed and validated, enriching 50 mL wastewater to 100 µL with limits of detection (LOD) being 0.005-0.5 ng L-1, limits of quantification (LOQ) being 0.01-1.0 ng L-1, recoveries ranging from 73.99 to 110.72%, and the intra- and inter-day precision's relative standard deviations less than 15%. In comparison to the time-consuming conventional column-based solid phase extraction, the entire MSPE procedure from sample pre-treatment to data acquisition could be finished in one hour, thus largely facilitating the WBE method for drug surveillance and control.

Real-Time Cardiac Abnormality Monitoring and Nursing for Patient Using Electrocardiographic Signals.

INTRODUCTION: Cardiovascular disease nursing is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. METHODS: This research reconstructed the vector model for arbitrary leads using the phase space-time-delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. RESULT: Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. After utilizing the algorithm in Section 3.1 to remove noise, the signal-to-noise ratio increased by 8.6%. A clipping algorithm was employed to identify waveforms significantly affected by external factors. Subsequently, a network model established by a generative algorithm was utilized. The accuracy for healthy patients reached 99.2%, while the accuracy for APB was 100%, for LBBB 99.32%, for RBBB 99.1%, and for P-wave peak 98.1%. CONCLUSION: By utilizing a three-dimensional model, detailed variations in electrocardiogram signals associated with different diseases can be observed. The clipping algorithm is effective in identifying perturbed and damaged waveforms. Automated neural networks can classify diseases and patient identities to facilitate precision nursing.

Adult classic Bartter syndrome: a case report with 5-year follow-up and literature review.

Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited. This case report describes the findings in a 20-year-old man who was admitted with hypokalemic paralysis, with clinical manifestations were similar to those of Gitelman syndrome (GS); however, the patient was later diagnosed to have BS Type 3 through genetic testing (NM_000085.4 (CLCNKB): c.1052G>T). A literature review showed that no homozygous mutations have been reported to date. After 5 years of treatment and follow-up, we found that this genotype requires high levels of potassium and is prone to urinary protein and metabolic syndrome. Distinguishing adult-onset BS from GS is challenging in clinical practice. However, genetic diagnosis can help solve this problem effectively, and genotypes play a guiding role in treatment planning.

UFPS: A unified framework for partially annotated federated segmentation in heterogeneous data distribution.

Partially supervised segmentation is a label-saving method based on datasets with fractional classes labeled and intersectant. Its practical application in real-world medical scenarios is, however, hindered by privacy concerns and data heterogeneity. To address these issues without compromising privacy, federated partially supervised segmentation (FPSS) is formulated in this work. The primary challenges for FPSS are class heterogeneity and client drift. We propose a unified federated partially labeled segmentation (UFPS) framework to segment pixels within all classes for partially annotated datasets by training a comprehensive global model that avoids class collision. Our framework includes unified label learning (ULL) and sparse unified sharpness aware minimization (sUSAM) for class and feature space unification, respectively. Through empirical studies, we find that traditional methods in partially supervised segmentation and federated learning often struggle with class collision when combined. Our extensive experiments on real medical datasets demonstrate better deconflicting and generalization capabilities of UFPS.

A mini-review on gene delivery technique using nanoparticles-mediated photoporation induced by nanosecond pulsed laser.

Nanosecond pulsed laser induced photoporation has gained increasing attention from scholars as an effective method for delivering the membrane-impermeable extracellular materials into living cells. Compared with femtosecond laser, nanosecond laser has the advantage of high throughput and low costs. It also has a higher delivery efficiency than continuous wave laser. Here, we provide an extensive overview of current status of nanosecond pulsed laser induced photoporation, covering the photoporation mechanism as well as various factors that impact the delivery efficiency of photoporation. Additionally, we discuss various techniques for achieving photoporation, such as direct photoporation, nanoparticles-mediated photoporation and plasmonic substrates mediated photoporation. Among these techniques, nanoparticles-mediated photoporation is the most promising approach for potential clinical application. Studies have already been reported to safely destruct the vitreous opacities in vivo by nanosecond laser induced vapor nanobubble. Finally, we discuss the potential of nanosecond laser induced phototoporation for future clinical applications, particularly in the areas of skin and ophthalmic pathologies. We hope this review can inspire scientists to further improve nanosecond laser induced photoporation and facilitate its eventual clinical application.

Spatial self-phase modulation excited by fractional-order linearly polarized vector fields.

Compared to the integer-order vector field, the fractional-order vector field has an additional degree of control freedom, which will bring rich photophysical properties and what we believe to be novel nonlinear optical phenomena. In this work, we theoretically and experimentally investigate the focusing, propagation, and spatial self-phase modulation (SSPM) of fractional-order linearly polarized vector fields (FLPVFs). It is shown that the weak focusing field of FLPVF exhibits an asymmetric intensity distribution. Intriguingly, its state of polarization (SoP) has a hybrid polarization distribution. When this focused FLPVF propagates to the far field in free space, its SoP degenerates into a localized linearly polarization distribution. However, after the focused FLPVF passes through an isotropic nonlinear Kerr medium, its SoP exhibits a hybrid polarization distribution. Additionally, unlike the self-diffraction intensity pattern of integer-order linearly polarized vector field (ILPVF) with a concentric multi-ring structure, the SSPM pattern of FLPVF is a symmetry broken self-diffraction intensity pattern. The presented work provides a nonlinear optics approach for manipulating both the SoP and intensity distributions of the light field.

Surveillance of ticks on a tropical island with introduced ungulates.

The abundance of hard ticks can be determined by abiotic factors and the presence of suitable hosts. Since deer represent important hosts for many tick species, it is imperative to investigate whether deer introduction will increase the number of ticks, which can transmit a wide variety of pathogens. The sika deer (Cervus nippon) was introduced to Green Island, Taiwan, to supply velvet antlers, a traditional Chinese medicine. However, they were later released into the wild after a steep decline in antler prices. We conducted surveys for questing ticks, ticks on rodents and shrews, and the fecal pellet groups of ungulates (deer and goats) in 31 transects within 3 habitat types (forest, grassland, and roadside) on Green Island every 2 months in 2019. A total of 5,321 questing ticks were collected. All collected ticks were Haemaphysalis mageshimaensis Saito and Hoogstraal, a species first identified on an island with an abundance of sika deer. Additionally, 48 ticks collected from 126 trapped rodents and shrews were almost invariably Ixodes granulatus (except for 1 larval Haemaphysalis sp.). We did not find a positive correlation between the number of questing ticks and the number of fecal pellet groups, suggesting that factors other than ungulate abundance affect tick abundance. Nevertheless, large populations of questing ticks along some roadsides suggest a high risk of tick-borne diseases to tourists on this tropical island.

Antibodies to S2 domain of SARS-CoV-2 spike protein in Moderna mRNA vaccinated subjects sustain antibody-dependent NK cell-mediated cell cytotoxicity against Omicron BA.1.

Vaccination with the primary two-dose series of SARS-CoV-2 mRNA protects against infection with the ancestral strain, and limits the presentation of severe disease after re-infection by multiple variants of concern (VOC), including Omicron, despite the lack of a strong neutralizing response to these variants. We compared antibody responses in serum samples collected from mRNA-1273 (Moderna) vaccinated subjects to identify mechanisms of immune escape and cross-protection. Using pseudovirus constructs containing domain-specific amino acid changes representative of Omicron BA.1, combined with domain competition and RBD-antibody depletion, we showed that RBD antibodies were primarily responsible for virus neutralization and variant escape. Antibodies to NTD played a less significant role in antibody neutralization but acted along with RBD to enhance neutralization. S2 of Omicron BA.1 had no impact on neutralization escape, suggesting it is a less critical domain for antibody neutralization; however, it was as capable as S1 at eliciting IgG3 responses and NK-cell mediated, antibody-dependent cell cytotoxicity (ADCC). Antibody neutralization and ADCC activities to RBD, NTD, and S1 were all prone to BA.1 escape. In contrast, ADCC activities to S2 resisted BA.1 escape. In conclusion, S2 antibodies showed potent ADCC function and resisted Omicron BA.1 escape, suggesting that S2 contributes to cross-protection against Omicron BA.1. In line with its conserved nature, S2 may hold promise as a vaccine target against future variants of SARS-CoV-2.

Massive anterior mediastinal lipoma causing cardiac arrest in a middle-aged male: a case report and literature review.

Lipoma is a common benign soft tissue tumor, but its size and location can lead to serious issues. We report a case of a 48 year-old male patient who experienced sudden cardiac arrest outside the hospital. After resuscitation and examination, we determined that this was due to a massive mediastinal lipoma compressing the lungs, leading to respiratory failure and pulmonary encephalopathy, ultimately resulting in cardiac arrest. This case serves as a reminder to promptly identify and manage chest lipomas to avoid compression and functional impairment of the respiratory system. Early evaluation and treatment of massive lipomas are crucial for preventing complications.

Dual-Antigen Subunit Vaccine Nanoparticles for Scrub Typhus.

Orientia tsutsugamushi is the causative pathogen of scrub typhus, an acute febrile disease prevalent in the Asia-Pacific region that is spread to people through chigger bites. Despite the emerging threat, there is no currently available vaccine against O. tsutsugamushi. Here, we developed dual-antigen subunit vaccine nanoparticles using recombinant 47 kD and 56 kD proteins, which are immunogenic outer membrane antigens of O. tsutsugamushi. The biocompatible protein vaccine nanoparticles were formed via desolvation of r56 or r47E antigens with acetone, coating with an additional layer of the 56 kD protein, and stabilization with reducible homobifunctional DTSSP and heterobifunctional SDAD crosslinkers. The dual-antigen subunit vaccine nanoparticles significantly improved antigen-specific antibody responses in vaccinated mice. Most importantly, the dual-antigen nanoparticles coated with an additional layer of the 56 kD protein were markedly more immunogenic than soluble antigens or single-antigen nanoparticles in the context of cellular immune responses. Given the significance of cellular immune responses for protection against O. tsutsugamushi, these results demonstrate the potent immunogenicity of dual-layered antigen nanoparticles and their potential as a promising strategy for developing vaccines against scrub typhus.

A Facile Synthetic Approach to UV-Degradable Hydrogels.

Light-degradable hydrogels have a wide range of application prospects in the field of biomedicine. However, the provision of a facile synthetic approach to light-degradable hydrogels under mild conditions remains a challenge for researchers. To surmount this challenge, a facile synthetic approach to UV-degradable hydrogels is demonstrated in this manuscript. Initially, an UV-degradable crosslinker (UVDC) having o-nitrobenzyl ester groups was synthesized in a single step through the employment of the Passerini three-component reaction (P-3CR). Both 1H NMR and MS spectra indicated the successful synthesis of high-purity UVDC, and it was experimentally demonstrated that the synthesized UVDC was capable of degradation under 368 nm light. Furthermore, this UVDC was mixed with 8-arm PEG-thiol (sPEG20k-(SH)8) to promptly yield an UV-degradable hydrogel through a click reaction. The SEM image of the fabricated hydrogel exhibits the favorable crosslinking network of the hydrogel, proving the successful synthesis of the hydrogel. After continuous 368 nm irradiation, the hydrogel showed an obvious gel-sol transition, which demonstrates that the hydrogel possesses a desirable UV-degradable property. In summary, by utilizing solely a two-step reaction devoid of catalysts and hazardous raw materials, UV-degradable hydrogels can be obtained under ambient conditions, which greatly reduces the difficulty of synthesizing light-degradable hydrogels. This work extends the synthetic toolbox for light-degradable hydrogels, enabling their accelerated development.

Magnetic Liposomes Infused with GPCR-Expressing Cell Membrane for Targeted Extraction Using Minimum Organic Solvent: An Investigative Study of Trace THC in Sewage.

Trace analysis of lipophilic substances in complex environmental, food, or biological matrices has proven to be a challenge, on account of their high susceptibility to adsorption by particulate matter and liquid-solid interfaces. For this purpose, liquid-liquid extraction (LLE) is often employed as the separation method, which uses water-immiscible organic solvents. As an alternative, magnetic solid-phase extraction (MSPE) allows for adsorption, separation, and recovery of analytes from large volumes of aqueous samples with minimum usage of organic solvents. However, the poor selectivity hampers its performance in various scenarios, especially in sewage samples where complicated and unpredictable interference exists, resulting in block of the active adsorption sites of the sorbent. To this end, we propose receptor-affinity MSPE employing magnetic liposomes decorated with cell membranes expressing G-protein-coupled receptor as the sorbents. Application of the novel sorbent CM@Lip@Fe infused with CB1 cannabinoid receptors was demonstrated for the targeted extraction and enrichment of tetrahydrocannabinol from sewage matrix. Thanks to the high affinity and molecular selectivity of the ligand-receptor interactions, a limit of quantitation of 5.17 ng/L was achieved coupled with HPLC-MS/MS in unfiltered raw sewage, featuring minimum usage of organic solvents, fivefold enhanced sensitivity, low sorbent dosage (75 mg/L of sewage), and high efficiency as major advantages over conventional LLE. This work establishes a framework for efficient separation of specific molecules from complex media, thus promising to extend and refine standard LLE as the clean-up procedure for trace analysis.

InSb-based saturable absorbers for ultrafast photonic applications.

Sb-related III-V compounds have recently gained great research interest owing to their excellent optical and electrical characteristics, which provide many possibilities in photonics and electronics. This study investigated the application of InSb films in ultrafast photonics. An InSb film was fabricated on the tapered zone of a microfiber, and its saturation intensity, modulation depth, and non-saturable loss were determined as 119.8 MW cm-2, 23.5%, and 27.3%, respectively. The structure of the electronic band and density of states of InSb were theoretically calculated. Notably, mode-locked and Q-switched fiber lasers were realised by incorporating the InSb-microfiber device into two different Er-doped fiber cavities. In the Q-switching state, the narrowest pulse duration was measured as 1.756 µs with a maximum single-pulse energy of 221.95 nJ and a signal-to-noise ratio of 60 dB. In the mode-locking operation, ultrafast lasers with a high signal-to-noise ratio (70 dB), a pulse width as narrow as 265 fs and a repetition rate of 49.51 MHz were acquired. Besides, the second-harmonic mode-locked state was built with an output power of 13.22 mW. In comparison with the reported laser performance with 2D materials as saturable absorbers, the InSb-based mode-locked and Q-switched fiber lasers proposed herein exhibit better comprehensive performance.

Toward a Smart Sensing System to Monitor Small Animal's Physical State via Multi-Frequency Resonator Array.

This article presents a highly scalable and rack-mountable wireless sensing system for long-term monitoring (i.e., sense and estimate) of small animal/s' physical state (SAPS), such as changes in location and posture within standard cages. The conventional tracking systems may lack one or more features such as scalability, cost efficiency, rack-mount ability, and light condition insensitivity to work 24/7 on a large scale. The proposed sensing mechanism relies on relative changes of multiple resonance frequencies due to the animal's presence over the sensor unit. The sensor unit can track SAPS changes based on changes in electrical properties in the sensors near fields, appearing in the resonance frequencies, i.e., an Electromagnetic (EM) Signature, within the 200 MHz-300 MHz frequency range. The sensing unit is located underneath a standard mouse cage and consists of thin layers of a reading coil and six resonators tuned at six distinct frequencies. ANSYS HFSS software is used to model and optimize the proposed sensor unit and calculate the Specific Absorption Rate (SAR) obtained under 0.05 W/kg. Multiple prototypes have been implemented to test, validate, and characterize the performance of the design by conducting in vitro and in vivo experiments on Mice. The in-vitro test results have shown a 15 mm spatial resolution in detecting the mouse's location over the sensor array having maximum frequency shifts of 832 kHz and posture detection with under 30° resolution. The in-vivo experiment on mouse displacement resulted in frequency shifts of up to 790 kHz, indicating the SAPS's capability to detect the Mice's physical state.

Impact of nanopore-based metagenome sequencing on tick-borne virus detection.

Introduction: We evaluated metagenomic nanopore sequencing (NS) in field-collected ticks and compared findings from amplification-based assays. Methods: Forty tick pools collected in Anatolia, Turkey and screened by broad-range or nested polymerase chain reaction (PCR) for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) and Jingmen tick virus (JMTV) were subjected to NS using a standard, cDNA-based metagenome approach. Results: Eleven viruses from seven genera/species were identified. Miviruses Bole tick virus 3 and Xinjiang mivirus 1 were detected in 82.5 and 2.5% of the pools, respectively. Tick phleboviruses were present in 60% of the pools, with four distinct viral variants. JMTV was identified in 60% of the pools, where only 22.5% were PCR-positive. CCHFV sequences characterized as Aigai virus were detected in 50%, where only 15% were detected by PCR. NS produced a statistically significant increase in detection of these viruses. No correlation of total virus, specific virus, or targeted segment read counts was observed between PCR-positive and PCR-negative samples. NS further enabled the initial description of Quaranjavirus sequences in ticks, where human and avian pathogenicity of particular isolates had been previously documented. Discussion: NS was observed to surpass broad-range and nested amplification in detection and to generate sufficient genome-wide data for investigating virus diversity. It can be employed for monitoring pathogens in tick vectors or human/animal clinical samples in hot-spot regions for examining zoonotic spillover.

Photothermal Controlled-Release Immunomodulatory Nanoplatform for Restoring Nerve Structure and Mechanical Nociception in Infectious Diabetic Ulcers.

Infectious diabetic ulcers (IDU) require anti-infection, angiogenesis, and nerve regeneration therapy; however, the latter has received comparatively less research attention than the former two. In particular, there have been few reports on the recovery of mechanical nociception. In this study, a photothermal controlled-release immunomodulatory hydrogel nanoplatform is tailored for the treatment of IDU. Due to a thermal-sensitive interaction between polydopamine-reduced graphene oxide (pGO) and the antibiotic mupirocin, excellent antibacterial efficacy is achieved through customized release kinetics. In addition, Trem2+ macrophages recruited by pGO regulate collagen remodeling and restore skin adnexal structures to alter the fate of scar formation, promote angiogenesis, accompanied by the regeneration of neural networks, which ensures the recovery of mechanical nociception and may prevent the recurrence of IDU at the source. In all, a full-stage strategy from antibacterial, immune regulation, angiogenesis, and neurogenesis to the recovery of mechanical nociception, an indispensable neural function of skin, is introduced to IDU treatment, which opens up an effective and comprehensive therapy for refractory IDU.

Antibody Responses to the SARS-CoV-2 Ancestral Strain and Omicron Variants in Moderna mRNA-1273 Vaccinated Active-Duty US Navy Sailors and Marines.

Omicron and its subvariants have steadily gained greater capability of immune escape compared to other variants of concern, resulting in an increased incidence of reinfections even among vaccinated individuals. We evaluated the antibody response to Omicron BA.1, BA.2, and BA.4/5 in US military members vaccinated with the primary 2-dose series of Moderna mRNA-1273 in a cross-sectional study. While nearly all vaccinated participants had sustained spike (S) IgG and neutralizing antibodies (ND50) to the ancestral strain, only 7.7% participants had detectable ND50 to Omicron BA.1 at 8 months postvaccination. The neutralizing antibody response to BA.2 and BA.5 was similarly reduced. The reduced antibody neutralization of Omicron correlated with the decreased antibody binding to the receptor-binding domain. The participants' seropositivity to the nuclear protein positively correlated with ND50. Our data emphasizes the need for continuous vigilance in monitoring for emerging variants and the need to identify potential alternative targets for vaccine design.