Association of novel DNAH11 variants with asthenoteratozoospermia lead to male infertility.

BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Effects of sleep on the glymphatic functioning and multimodal human brain network affecting memory in older adults.

Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such as the middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling of rich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks.

Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans.

BACKGROUND: The association between the TDRD6 variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6 was found to be associated with oligoasthenoteratozoospermia (OAT). METHODS: Whole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6 in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6-knockout mice were generated using the CRISPR-Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment. RESULTS: Bi-allelic TDRD6 variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6 variants. ScRNA-seq analysis of germ cells from a patient with TDRD6 variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation. CONCLUSION: Our findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6 variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6 variants, providing insights for potential clinical treatment strategies.

Micro Reference Electrode with an Ultrathin Ionic Path.

Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

Novel MEIOB pathogenic variants including a homozygous non-canonical splicing variant, cause meiotic arrest and human non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is the most severe form of human male infertility, and the genetic causes of NOA with meiotic arrest remain largely unclear. In this study, we identified novel compound heterozygous MEIOB variants (c.814C > T: p.R272X and c.976G > A: p.A326T) and a previously undescribed homozygous non-canonical splicing variant of MEIOB (c.528 + 3A > C) in two NOA-affected individuals from two irrelevant Chinese families. MEIOB missense variant (p.A326T) significantly reduced protein abundance and nonsense variant (p.R272X) produced a truncated protein. Both of two variants impaired the MEIOB-SPATA22 interaction. The MEIOB non-canonical splicing variant resulted in whole Exon 6 skipping by minigene assay, which was predicted to produce a frameshift truncated protein (p.S111Rfs*32). Histological and immunostaining analysis indicated that both patients exhibited a similar phenotype as we previously reported in Meiob mutant mice, that is, absence of spermatids in seminiferous tubules and meiotic arrest. Our study identified three novel pathogenic variants of MEIOB in NOA patients, extending the mutation spectrum of the MEIOB and highlighting the contribution of meiotic recombination related genes in human fertility.

Non-Hermitian Moiré Valley Filter.

A valley filter capable of generating a valley-polarized current is a crucial element in valleytronics, yet its implementation remains challenging. Here, we propose a valley filter made of a graphene bilayer which exhibits a 1D moiré pattern in the overlapping region of the two layers controlled by heterostrain. In the presence of a lattice modulation between layers, electrons propagating in one layer can have valley-dependent dissipation due to valley asymmetric interlayer coupling, thus giving rise to a valley-polarized current. Such a process can be described by an effective non-Hermitian theory, in which the valley filter is driven by a valley-resolved non-Hermitian skin effect. Nearly 100% valley polarization can be achieved within a wide parameter range and the functionality of the valley filter is electrically tunable. The non-Hermitian topological scenario of the valley filter ensures high tolerance against imperfections such as disorder and edge defects. Our work opens a new route for efficient and robust valley filters while significantly relaxing the stringent implementation requirements.

One-Pot Divergent Synthesis of a 13-Ring Triquinone and its Facile Conversion to a [4.4.4]Tridecastarphene.

Acenes are notable for their optoelectronic properties and applications in organic electronics. Starphenes are structurally related molecules possessing three acene arms that radiate linearly from a central benzene ring (i. e., linearly annellated triphenylenes). Large starphenes have been prepared using convergent syntheses involving transition metal catalyzed cyclotrimerizations of either preformed acenes or arynes. Here, we report a one-pot divergent synthesis of a 13-ring triquinone that is readily converted to a [4.4.4]tridecastarphene derivative. The one-pot procedure involves the sequential reactions of three 1,4-anthraquinones with o-quinodimethane derivatives that are generated sequentially from a stable, trisulfone precursor. The resulting [4.4.4]tridecastarphene derivative bearing p-(t-butyl)phenyl substituents was characterized by 1H NMR, 13C NMR and UV-vis spectroscopies, as well as mass spectrometry, cyclic voltammetry and differential pulse voltammetry. Theoretical and experimental studies reveal a relatively high-lying HOMO orbital (about -4.70 to -4.86 eV) and a relatively small HOMO-LUMO gap (2.1 eV), suggesting utility as a p-type organic semiconductor. Our [4.4.4]tridecastarphene derivative photooxidizes in a CH2Cl2 solution exposed to ambient light and air with a half-life of 150 minutes at room temperature, but shows no sign of degradation after 12 months in the solid-state. Our [4.4.4]tridecastarphene derivative also shows excellent solubility in a number of organic solvents including dichloromethane, chloroform and toluene, potentially enabling printed electronic applications.

Adherence to a healthy sleep pattern and risk of urologic cancers: A large prospective cohort study.

OBJECTIVE: A variety of unhealthy sleep behaviors have been shown to be associated with an increased risk of urologic cancers. However, little is known about the association between the overall sleep patterns and urologic cancers. To prospectively investigate the associations between a healthy sleep pattern and the risks of urologic cancers, including bladder cancer (BCa) and renal cell carcinoma (RCC). METHODS: In this prospective cohort study, 377,144 participants free of cancer at baseline were recruited from the UK Biobank. Data on sleep behaviors were collected through questionnaires at recruitment. The incident urologic cancer cases were determined through linkage to national cancer and death registries. We established a healthy sleep score according to five sleep traits (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness). Cox proportional hazard regression models were used to calculate the adjusted hazard ratios and 95% confidence intervals to assess the relationship between the healthy sleep score and the risk of urologic cancers. RESULTS: During a median of ≥9 years of follow-up, we identified 1986 incident urologic cancer cases, including 1272 BCa cases and 706 RCC cases. Compared with the participants with a poor sleep pattern (score of 0-2), the multivariable-adjusted hazard ratio and 95% confidence interval were 0.85 (0.75 to 0.96) for urologic cancers, 0.80 (0.68 to 0.93) for BCa, and 0.91 (0.74, 1.12) for RCC, respectively, for those with the healthier sleep pattern (score of 4-5). CONCLUSION: Our results indicate that a healthy sleep pattern is associated with lower risks of urologic cancers.

Metabolic profile characterization of voxelotor in human urine based on in vivo and in vitro models for doping control.

Voxelotor was approved for the treatment of sickle cell anemia as a potent hemoglobin S polymerization inhibitor. Owing to its ability to affect blood components and its potential to enhance athletic performance, voxelotor was included in the prohibited list issued by the World Anti-Doping Agency in 2023, banning its use both in and out of competition. This study aimed to comprehensively investigate the metabolic profile of voxelotor in human urine and identify suitable metabolites for long-term analytical retrospectivity in doping control. A novel strategy for metabolite identification was established by combining in vivo human administration with isotope labeling-based in vitro metabolism analysis. A single microdose of voxelotor was administered orally to five volunteers, and urine samples were collected for up to 28 days post-administration. Concurrently, in vitro incubation of human liver microsomes with voxelotor and D3-voxelotor was conducted, and the microsomal incubates were analyzed via liquid chromatography-high-resolution mass spectrometry. Targeted metabolite searches in human urine samples and automated nontargeted screening of isotope metabolite ion pairs in incubation samples led to the discovery of 9 phase I metabolites and 23 phase II metabolites. Analysis of the urine excretion curves revealed that 4 metabolites, along with voxelotor, were suitable for long-term anti-doping monitoring, with a detection window exceeding 20 days. Using both in vivo and in vitro metabolic models, this study provides comprehensive insight into the metabolic profile of voxelotor in human urine for the first time, enhancing the capacity for doping screening and extending the retrospectivity of voxelotor detection.

Exploring the Efficacy of Hydroxybenzoic Acid Derivatives in Mitigating Jellyfish Toxin-Induced Skin Damage: Insights into Protective and Reparative Mechanisms.

The escalation of jellyfish stings has drawn attention to severe skin reactions, underscoring the necessity for novel treatments. This investigation assesses the potential of hydroxybenzoic acid derivatives, specifically protocatechuic acid (PCA) and gentisic acid (DHB), for alleviating Nemopilema nomurai Nematocyst Venom (NnNV)-induced injuries. By employing an in vivo mouse model, the study delves into the therapeutic efficacy of these compounds. Through a combination of ELISA and Western blot analyses, histological examinations, and molecular assays, the study scrutinizes the inflammatory response, assesses skin damage and repair mechanisms, and investigates the compounds' ability to counteract venom effects. Our findings indicate that PCA and DHB significantly mitigate inflammation by modulating critical cytokines and pathways, altering collagen ratios through topical application, and enhancing VEGF and bFGF levels. Furthermore, both compounds demonstrate potential in neutralizing NnNV toxicity by inhibiting metalloproteinases and phospholipase-A2, showcasing the viability of small-molecule compounds in managing toxin-induced injuries.

Achieving an optimal pregnancy outcome through the combined utilization of micro-TESE and ICSI in cryptorchidism associated with a non-canonical splicing variant in RXFP2.

PURPOSE: To identify the genetic cause of a cryptorchidism patient carrying a non-canonical splicing variant highlighted by SPCards platform in RXFP2 and to provide a comprehensive overview of RXFP2 variants with cryptorchidism correlation. METHODS: We identified a homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing in a case with cryptorchidism and non-obstructive azoospermia (NOA). As the pathogenicity of this non-canonical splicing variant remained unclear, we initially utilized the SPCards platform to predict its pathogenicity. Subsequently, we employed a minigene splicing assay to further evaluate the influence of the identified splicing variant. Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection (ICSI) was performed. PubMed and Human Genome Variant Database (HGMD) were queried to search for RXFP2 variants. RESULTS: We identified a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in RXFP2, and confirmed this variant caused aberrant splicing of exons 15 and 16 of the RXFP2 gene: 11 bases were added in front of exon 16, leading to an abnormal transcript initiation and a frameshift. Fortunately, the patient successfully obtained his biological offspring through micro-TESE combined with ICSI. Four cryptorchidism-associated variants in RXFP2 from 90 patients with cryptorchidism were identified through a literature search in PubMed and HGMD, with different inheritance patterns. CONCLUSION: This is the first cryptorchidism case carrying a novel causative non-canonical splicing RXFP2 variant. The combined approach of micro-TESE and ICSI contributed to an optimal pregnancy outcome. Our literature review demonstrated that RXFP2 variants caused cryptorchidism in a recessive inheritance pattern, rather than a dominant pattern.

Comparative analysis of PacBio and ONT RNA sequencing methods for Nemopilema Nomurai venom identification.

Recent studies on marine organisms have made use of third-generation sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT). While these specialized bioinformatics tools have different algorithmic designs and performance capabilities, they offer scalability and can be applied to various datasets. We investigated the effectiveness of PacBio and ONT RNA sequencing methods in identifying the venom of the jellyfish species Nemopilema nomurai. We conducted a detailed analysis of the sequencing data from both methods, focusing on key characteristics such as CD, alternative splicing, long-chain noncoding RNA, simple sequence repeat, transcription factor, and functional transcript annotation. Our findings indicate that ONT generally produced higher raw data quality in the transcriptome analysis, while PacBio generated longer read lengths. PacBio was found to be superior in identifying CDs and long-chain noncoding RNA, whereas ONT was more cost-effective for predicting alternative splicing events, simple sequence repeats, and transcription factors. Based on these results, we conclude that PacBio is the most specific and sensitive method for identifying venom components, while ONT is the most cost-effective method for studying venogenesis, cnidocyst (venom gland) development, and transcription of virulence genes in jellyfish. Our study has implications for future sequencing technologies in marine jellyfish, and highlights the power of full-length transcriptome analysis in discovering potential therapeutic targets for jellyfish dermatitis.

Research on Pipeline Stress Detection Method Based on Double Magnetic Coupling Technology.

Oil and gas pipelines are subject to soil corrosion and medium pressure factors, resulting in stress concentration and pipe rupture and explosion. Non-destructive testing technology can identify the stress concentration and defect corrosion area of the pipeline to ensure the safety of pipeline transportation. In view of the problem that the traditional pipeline inspection cannot identify the stress signal at the defect, this paper proposes a detection method using strong and weak magnetic coupling technology. Based on the traditional J-A (Jiles-Atherton) model, the pinning coefficient is optimized and the stress demagnetization factor is added to establish the defect of the ferromagnetic material. The force-magnetic relationship optimization model is used to calculate the best detection magnetic field strength. The force-magnetic coupling simulation of Q235 steel material is carried out by ANSYS 2019 R1 software based on the improved J-A force-magnetic model. The results show that the effect of the stress on the pipe on the magnetic induction increases first and then decreases with the increase in the excitation magnetic field strength, and the magnetic signal has the maximum proportion of the stress signal during the excitation process; the magnetic induction at the pipe defect increases linearly with the increase in the stress trend. Through the strong and weak magnetic scanning detection of cracked pipeline materials, the correctness of the theoretical analysis and the validity of the engineering application of the strong and weak magnetic detection method are verified.

Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice.

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin's beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila. This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin's potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.

Refinement of nanoporous copper by dealloying the Al-Cu alloy in NaOH solution containing sodium dodecyl sulfate.

This work reports the refinement of nanoporous copper (NPC) ligaments by introducing the sodium dodecyl sulfate (SDS) surfactant in the dealloying process. The Al80Cu20 (at%) alloy precursor is chemically dealloyed in a mixed solution of NaOH and SDS surfactant, producing NPC with a hierarchical microstructure. Micron-scaled skeletons that build up higher level networks consist of geometrically similar nano-scaled bi-continuous ligament-pore networks at the lower level. It has been found that the size of the ligaments in the lower level networks reduces from ∼32 nm to ∼24 nm with increasing SDS concentration to 1 mM. Further increasing the SDS concentration to 5 mM only leads to a slight ligament size decrease to ∼21 nm. Remarkably, nano-sized cones are formed on the lower level network surface in the dealloying solution containing 1 mM SDS, and the cone number greatly rises when the SDS concentration increases to 5 mM. The surface diffusivity of Cu adatoms is evaluated based on the experimental data, and the refinement of the ligament as well as the formation of cones are associated with the decreased surface diffusivity and the retarded Cu adatom motions with the addition of SDS. Quantum chemical calculations and molecular dynamics simulations are performed to model the adsorption behavior of SDS. It has been found that the SDS-substrate interaction increases with the number of SDS molecules before SDS reaches saturation.

Research on the Forward Solving Method of Defect Leakage Signal Based on the Non-Uniform Magnetic Charge Model.

Pipeline magnetic flux leakage inspection is widely used in the evaluation of material defect detection due to its advantages of having no coupling agent and easy implementation. The quantification of defect size is an important part of magnetic flux leakage testing. Defects of different geometrical dimensions produce signal waveforms with different characteristics after excitation. The key to achieving defect quantification is an accurate description of the relationship between the magnetic leakage signal and the size. In this paper, a calculation model for solving the defect leakage field based on the non-uniform magnetic charge distribution of magnetic dipoles is developed. Based on the traditional uniformly distributed magnetic charge model, the magnetic charge density distribution model is improved. Considering the variation of magnetic charge density with different depth positions, the triaxial signal characteristics of the defect are obtained by vector synthesis calculation. Simultaneous design of excitation pulling experiment. The leakage field distribution of rectangular defects with different geometries is analyzed. The experimental results show that the change in defect size will have an impact on the area of the defect leakage field distribution, and the larger the length and wider the width of the defect, the more sensitive the impact on the leakage field distribution. The solution model is consistent with the experimentally obtained leakage signal distribution law, and the model is a practical guide by which to improve the quality of defect evaluation.

Weak Magnetic Internal Signal Characteristics of Pipe Welds under Internal Pressure.

Weak magnetic detection technology is an effective method to identify stress-induced damage to ferromagnetic materials, and it especially possesses great application potential in long-distance oil and gas pipeline weld crack detection. In the process of pipeline operation, due to internal pressure and external loads, local stress concentration may be generated, and partial stress concentration may lead to local cracks and expansion of the pipe. In order to improve the accuracy of magnetic signal analysis for ferromagnetic materials under internal pressure, the causes of magnetic signal generation at pipeline welds were analyzed from a microscopic perspective. The distributions of magnetic signals at pipeline welds, weld cracks, and base metal cracks under different internal pressures were numerically analyzed. The variation trends of magnetic signal characteristics, such as peak values of axial and radial components, gradient K, maximum gradient Kmax, and gradient energy factor S(K), were analyzed. In addition, experiments were carried out to verify the numerical data. It was revealed that with the elevation of internal pressure, the peak values of the axial and radial components, gradient K, maximum gradient Kmax, and gradient energy factor S(K) linearly increased. However, the magnitude and average change of S(K) were larger, which can more directly indicate variations of magnetic signals. The radial growth rate νy of S(K) was 3.24% higher than the axial growth rate νx, demonstrating that the radial component of the magnetic signal was more sensitive to variations of stress. This study provided a theoretical and experimental basis for detection of stress-induced damage to long-distance oil and gas pipelines.

The Signal Characteristics of Oil and Gas Pipeline Leakage Detection Based on Magneto-Mechanical Effects.

In order to solve the problem of the quantification of detection signals in the magnetic flux leakage (MFL) of defective in-service oil and gas pipelines, a non-uniform magnetic charge model was established based on magnetic effects. The distribution patterns of magnetic charges under different stresses were analyzed. The influences of the elastic load and plastic deformation on the characteristic values of MFL signals were quantitatively assessed. The experimental results showed that the magnetic charge density was large at the edges of the defect and small at the center, and approximately decreased linearly with increasing stress. The eigenvalues of the axial and radial components of the MFL signals were compared, and it was found that the eigenvalues of the radial component exhibited a larger decline rate and were more sensitive to stress. With the increase in the plastic deformation, the characteristic values of the MFL signals initially decreased and then increased, and there was an inflection point. The location of the inflection point was associated with the magnetostriction coefficient. Compared with the uniform magnetic charge model, the accuracy of the axial and radial components of the MFL signals in the elastic stage of the improved magnetic charge model rose by 17% and 16%, respectively. The accuracy of the axial and radial components of the MFL signals were elevated by 9.15% and 9%, respectively, in the plastic stage.

Remote Manipulation of ROS-Sensitive Calcium Channel Using Near-Infrared-Responsive Conjugated Oligomer Nanoparticles for Enhanced Tumor Therapy In Vivo.

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca2+) channels is of great significance in the treatment of tumors. Here, a simple ROS generation system is developed to activate ROS-sensitive ion channels for enhancing calcium-cascade-mediated tumor cell death under near-infrared (NIR) light irradiation. Upon irradiation with an 808 nm laser, a low-lethality amount of ROS facilitates plasmid transient potential receptor melastatin-2 (pTRPM2) gene release via cleavage of the Se-Se bonds, which contributed to enhancing the expression of TRPM2 in tumor cells. Meanwhile, ROS could potently activate TRPM2 for Ca2+ influx to inhibit early autophagy and to further induce intracellular ROS production, which ultimately led to cell death in TRPM2 expressing tumor cells. Both in vitro and in vivo data show that nanoparticles have an excellent therapeutic effect on cancer upon NIR light. This work presents a simple modality based on NIR light to remotely control the ROS-sensitive ion channel for cancer therapy.

Molecular and Genetics-Based Systems for Tracing the Evolution and Exploring the Mechanisms of Human Norovirus Infections.

Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.