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Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+ transporting 2 oblivion (Atp2b2 Oblivion) heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender, age and number were selected as the control group. Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay. Hair bundle structures were detected by scanning electron microscopy (SEM), and mitochondria and ribbon synapse structures were observed by transmission electron microscopy (TEM). Vestibular evoked potential (VsEP), vestibular evoked myogenic potential (VEMP), rotarod rod test, and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice. Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old. No visible structural abnormality in the hair bundle could be seen through SEM. TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice, while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site. VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice. Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice (P

There are no Food and Drug Administration‐approved drugs for treating noise‐induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM‐encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro‐computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained‐release and long‐term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug‐based treatment of NIHL. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to assess the effect of chromosomal reciprocal translocation on meiotic segregation products of non-translocation chromosomes. A total of 744 reciprocal translocation carriers and 875 non-carriers were included in this study. A total of 6,832 blastocysts were biopsied and tested by next-generation sequencing. Blastocysts from the carrier group were classified into five subgroups according to the theoretical segregation pattern of quadrivalent structure. For carrier patients, normal meiotic segregation products of the non-translocation chromosome were classified after excluding the segregation modes of the quadrivalent structure. The proportion of normal non-translocation chromosome meiotic segregation products was similar between the carrier and noncarrier groups (p = 0.69). The generalized Estimation Equation revealed that there was no correlation between reciprocal translocation and meiotic segregation products of non-translocation chromosomes. Moreover, subgroup analyses showed that the segregation modes of quadrivalent structure (p = 0.00) and carrier's gender (p = 0.00) may affect the meiotic segregation products of non-translocation chromosomes. In conclusion, reciprocal translocation does not directly reduce the proportion of normal segregation products of non-translocation chromosomes. The difference among subgroups of different quadrivalent segregation patterns implied that interchromosomal effect may exist but the high incidence of chromosomal abnormalities for reciprocal translocation carriers should not be attributed to interchromosomal effect. [ABSTRACT FROM AUTHOR]

While urban green spaces (UGSs) are important places for residents' leisure activities, studies describing the long-term daily UGS usage of residents (including the total number of activities, the types of activities, and the touring experience) have not been conducted due to difficulties in data collection. Based on social media text data (SMTD), in this study, the total number of daily activities, the intensities of optional and social activities, and the daily touring experience in 100 UGSs in Xiamen, China, were inferred based on the ERNIE 3.0 text pre-training semantic classification model. Based on this, linear regression modeling was applied to analyze the internal environmental factors of the effects of places and external urban form factors regarding daily UGS usage. The research results revealed the following. (1) A descriptive study was conducted on the total numbers, types, and touring experience of activities using SMTD, and the results were verified by line transect surveys, management statistics, and a publicly available dataset. (2) The number of human activities in UGSs was found to be significantly influenced by historical and cultural facilities, nighttime lighting, population density, and the proportion of the floating population. (3) During the daytime, optional activities were found to be significantly influenced by the park type and historical and cultural facilities, and social activities were found to be significantly influenced by historical and cultural facilities and population density. In the evening, optional activities were found to be significantly influenced by the park type, historical and cultural facilities, nighttime lighting, and the proportion of the floating population, and social activities were found to be influenced by the proportion of the floating population. (4) Regarding the touring experience, in the daytime, the park type, green space ratio, and proportion of the floating population had significant effects on the touring experience. In the evening, the park type, historical and cultural facilities, and security factors were found to have significant effects on the touring experience. The methodology and findings of this study aid in the understanding of the differences in daytime and nighttime activities, and in the discovery of planning tools to promote human leisure activities in UGSs. [ABSTRACT FROM AUTHOR]

The efficient dispersion of particles is a prerequisite for the efficient flotation of fine smithsonite. However, unavoidable ions (Ca2+) in the pulp have become a challenge for the efficient separation of fine smithsonite, due to the high content of pulp and small radius of hydrated ions. Therefore, the dispersion behavior and mechanism of Ca2+ action on smithsonite are important for improving the efficiency of smithsonite flotation. In this study, the effects of Ca2+ on the dispersion behavior of fine smithsonite were studied using a turbidity test. The results showed that the dispersion behavior of smithsonite was good in the absence of Ca2+ at a range of pH = 4–12. However, the measured turbidity values of smithsonite decreased with the addition of calcium ions. In particular, the dispersion behavior of smithsonite became worse at pH > 10. Zeta potential test results showed that the smithsonite's surface potential shifted positively, and the absolute value of potential decreased in the presence of Ca2+. The results of X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) analysis showed that calcium ions were adsorbed on the smithsonite surface, which may have caused ion exchange or the generation of calcium hydroxide precipitation leading to particle coalescence behavior. The calculations of solution chemistry and DLVO theory indicated that calcium ions adsorbed on the surface of smithsonite to form Ca(OH)+ or precipitation, which reduced the potential energy of interparticle interactions and led to the disruption of dispersion behavior of smithsonite. [ABSTRACT FROM AUTHOR]

In this study, the calcium gangue material calcite (−10 μm) was used to investigate the effects of different kinds of metal ions and dosages on the dispersion behavior of calcite. The test results showed that the dispersion behavior of calcite was poor under strongly alkaline conditions without the addition of metal ions, and the reason for that was calcite dissolved ions. The degree of influence of different metal ions on calcite dispersion behavior was Fe3+ > Mg2+ > Na+. The three metal ion dosage tests showed that the dispersion behavior of calcite became poorer with the increase of metal ion dosage. This mainly showed that with the increase of Na+ dosage, the trend of the dispersion behavior of calcite was not obvious, but with the increase of Fe3+ and Mg2+ dosage, the trend of calcite dispersion behavior changed more. The dispersion behavior of calcite was devastated by 5 × 10−4 mol/L Fe3+ at pH = 4–12. The different mechanisms of the three metal ions were identified by zeta potential, solution chemistry, and XPS analysis. Na+ only changed the zeta potential value of the calcite surface, which acted as a compressed electric double layer. However, the formation of metal hydroxide species or metal hydroxide surface precipitation due to the adsorption of Fe3+ and Mg2+ on the mineral surface resulted in the change of the dispersion behavior of calcite. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery is an effective therapy for type 2 diabetes mellitus (T2DM) and obesity. Euglycaemic ketoacidosis (EKA) has been reported in patients taking sodium-glucose cotransporter 2 (SGLT2) inhibitors after bariatric surgery. Cases of T2DM complicated with EKA without SGLT2 inhibitors after bariatric surgery are rarely reported. Purpose: To present a case report of a T2DM patient (without SGLT2 inhibitor use) who developed EKA soon after laparoscopic sleeve gastrectomy. Methods: Clinical records and interviews were used. Results: A 35-year-old female patient was diagnosed with T2DM and obesity. The patient underwent laparoscopic sleeve gastrectomy to lose weight and control her blood glucose levels. Her daily fluid intake was 800– 1000 mL, and her daily caloric intake was less than 500 kcal during the first days after the surgery. She was prescribed degludec insulin, metformin and dulaglutide and her blood sugar was lower than 13.9 mmol/L. On postoperative Day 6, the patient complained of fatigue and vomiting. Blood gas analysis and urine analysis supported the diagnosis of ketoacidosis. Fluid resuscitation, insulin and glucose were administered to the patient immediately. On postoperative Day 8, the patient recovered without any symptoms. Conclusion: We report an extremely rare case of T2DM in which the patient developed EKA after laparoscopic sleeve gastrectomy owing to extremely low-calorie intake and dehydration. Physicians should be on alert for ketoacidosis in patients with T2DM after bariatric surgery with an euglycaemic status, even without the use of SGLT2 inhibitors or the presence of stresses, such as infection.Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees. [ABSTRACT FROM AUTHOR]

Tumor-induced rickets/osteomalacia (TIR/O) severely impairs bone microarchitecture and bone strength. However, no study has described the microarchitectural quality of bone in adolescent patients with TIR/O. TIR/O affects bone quality more severely than the inherited causes of hypophosphatemia, the most common form of which is X-linked hypophosphatemia (XLH). Nevertheless, differences of the microarchitectural quality of the bone between TIR/O and XLH have never been clarified. Therefore, in this study, we used high-resolution peripheral quantitative computed tomography to assess bone microarchitecture in five Chinese adolescent TIR/O patients, and these were compared with 15 age- and gender-matched XLH patients as well as 15 age- and gender-matched healthy controls. Compared with the healthy controls, the TIR/O patients presented with significantly lower volumetric bone mineral densities (vBMDs), severely affected bone microarchitecture, and profoundly weaker bone strength. The distal tibia was more severely affected than the distal radius. Compared with the XLH patients, the TIR/O patients showed deteriorated bone quality notably at the distal tibia and in the cancellous compartment, reflected by 45.9% lower trabecular vBMD (p = 0.029), 40.2% lower trabecular fraction (p = 0.020), 40.6% weaker stiffness (p = 0.058), and 42.7% weaker failure load (p = 0.039) at the distal tibia. The correlation analysis showed that a higher level of serum FGF23 and a lower level of serum phosphate were associated with a poorer bone microarchitecture and a weaker estimated bone strength in the hypophosphatemic patients of our study. In conclusion, our study demonstrated significantly lower vBMDs, severely impaired bone microarchitecture, and profoundly weaker bone strength in Chinese adolescent patients with TIR/O, notably at the distal tibia, compared with the same parameters in age- and sex-matched healthy controls and XLH patients, which was possibly caused by excessive FGF23 production and secretion, chronically severe hypophosphatemia, and weak mechanical stimulus at the lower extremities. These findings further our understanding of the impact of different kinds of hypophosphatemic rickets/osteomalacia on bone quality. [ABSTRACT FROM AUTHOR]

This paper presents a general modeling method for threshold-type multivalued memristors. Through this memristor modeling method, it is very simple to establish threshold-type memristor behavior models with different numbers of memristance elements, and these models are verified by numerical MATLAB simulations. A corresponding circuit-level SPICE model of the ternary memristor behavior model is developed and simulated in LTspice, shown to be consistent with the MATLAB results. Finally, the SPICE model is used to design the AND gate, OR gate, and three NOT gates of ternary state-based logic, and the effectiveness of the circuit is proved by LTSpice simulation. [ABSTRACT FROM AUTHOR]

In children and adolescents, distinguishing tumor‐induced rickets/osteomalacia (TIR/O) from hereditary hypophosphatemic rickets/osteomalacia (HR/O) is a medical challenge. We retrospectively studied 10 Chinese children and adolescents with TIR/O who underwent surgery at a mean age of 17.4 ± 2.1 years and compared their characteristics to 24 age‐ and sex‐matched patients with X‐linked hypophosphatemia (XLH). Positive family history of HR/O and dental problems, such as enamel hypoplasia and dental abscess, were reported in 8 (33.3%) and 5 (20.8%) patients with XLX, respectively, but not in patients with TIR/O. In addition, in comparison with XLH patients, TIR/O patients had an older disease onset age (150 versus 24 months, p < 0.001), a higher height standard deviation score (SDS; −1.2 ± 1.8 versus −4.0 ± 1.4, p < 0.001), a lower Z‐score of bone mineral density (BMD) at lumbar spine (LS) (−3.9 [6.0] versus +1.8 [7.0], p < 0.001), and a higher serum intact fibroblast growth factor 23 (FGF23) level (500.27 ± 87.20 versus 121.71 ± 70.94 pg/mL, p < 0.001), corresponding to a lower serum phosphate level (0.52 ± 0.07 versus 0.64 ± 0.11 mmol/L, p = 0.005) and a higher serum alkaline phosphatase (ALP) level (557 [631] versus 305 [249] U/L, p = 0.005). We generated receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). The AUCs of onset age, FGF23, and LS Z‐score were equal to 1, suggesting that these are excellent indices for the differential diagnosis between TIR/O and XLH. In summary, our study furthers our understanding of the spectrum of clinical, biochemical, and pathologic findings associated with TIR/O. For children and adolescent patients with HR/O, a comprehensive and careful clinical and laboratory evaluation is of great importance, and we recommend enquiry of the family history, onset age, and dental problems, as well as measurement of serum FGF23 and BMD. © 2021 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Orthogonal time-frequency space (OTFS) bears the potential to achieve excellent performance in high mobility scenarios. However, conventional linear equalizer performs poorly. In this letter, we propose a novel two-stage equalizer, wherein received signals are judiciously processed in two domains. First, in the time-frequency domain, a sliding window-assisted minimum mean square error (SW-MMSE) equalizer is proposed to restrict the inter-carrier interference effectively. Then in the second stage, a delay-doppler domain equalizer further mitigates the residual inter-symbol interference of the first stage. Our proposed two-stage equalizer enjoys low implementation complexity, and simulation validates its performance advantage over the conventional one-stage MMSE equalizer. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy is limited. Auditory neuropathies (AN) were proved to play a substantial role in SNHL recently, and spiral ganglion neuron (SGN) dysfunction is a dominant pathogenesis of AN. Auditory pathway is a high energy consumption system, and SGNs required sufficient mitochondria. Mitochondria are known treatment target of SNHL, but mitochondrion mechanism and pathology in SGNs are not valued. Mitochondrial dysfunction and pharmacological therapy were studied in neurodegeneration, providing new insights in mitochondrion-targeted treatment of AN. In this review, we summarized mitochondrial biological functions related to SGNs and discussed interaction between mitochondrial dysfunction and AN, as well as existing mitochondrion treatment for SNHL. Pharmaceutical exploration to protect mitochondrion dysfunction is a feasible and effective therapeutics for AN. [ABSTRACT FROM AUTHOR]

Many kinds of lymphocytes are involved in Schistosoma japonicum (S. japonicum) infection-induced disease. γδ T cells comprise a small number of innate lymphocytes that quickly respond to foreign materials. In this study, the role of γδ T cells in the lung of S. japonicum -infected C56BL/6 mice was investigated. The results demonstrated that S. japonicum infection induces γδ T cell accumulation in the lung, expressing higher levels of CD25, MHCII, CD80, and PDL1, and lower levels of CD127 and CD62L (P < 0.05). The intracellular cytokines staining results illustrated higher percentages of IL-4-, IL-10-, IL-21-, and IL-6-producing γδ T cells and lower percentages of IFN-γ-expressing γδ T cells in the lung of infected mice (P < 0.05). Moreover, the granuloma size in lung tissue was significantly increased in Vδ−/− mice (P < 0.05). In the lung of S. japonicum -infected Vδ−/− mice, both type 1 and type 2 immune responses were decreased significantly (P < 0.05). In addition, the expression of CD80 and CD69 on B cells was decreased significantly (P < 0.05), and the SEA-specific antibody was markedly decreased (P < 0.05) in the blood of infected Vδ−/− mice. In conclusion, this study indicates that γδ T cells could adjust the Th2 dominant immune response in the lung of S. japonicum -infected mice. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) play an important role in regulating immune responses during pathogen infection. However, roles of TLRs on T cells reside in the mesenteric lymph node (MLN) were not be fully elucidated in the course of S. japonicum infection. In this study, T lymphocytes from the mesenteric lymph node (MLN) of S. japonicum-infected mice were isolated and the expression and roles of TLR2, TLR3, TLR4, and TLR7 on both CD4+ and CD8+ T cells were compared. We found that the expression of TLR7 was increased in the MLN cells of S. japonicum-infected mice, particularly in CD4+ and CD8+ T cells (P < 0.05). R848, a TLR7 agonist, could enhance the production of IFN-γ from MLN T cells of infected mice (P < 0.05), especially in CD8+ T cells (P < 0.01). In TLR7 gene knockedout (KO) mice, the S. japonicum infection caused a significant decrease (P < 0.05) of the expression of CD25 and CD69, as well as the production of IFN-γ and IL-4 inducted by PMA plus ionomycin on both CD4+ and CD8+ T cells. Furthermore, the decreased level of IFN-γ and IL-4 in the supernatants of SEA- or SWA-stimulated mesenteric lymphocytes was detected (P < 0.05). Our results indicated that S. japonicum infection could induce the TLR7 expression on T cells in the MLN of C57BL/6 mice, and TLR7 mediates T cell response in the early phase of infection. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that CD103 is an important marker for tissue-resident memory T cells (TRM) which plays an important role in anti-infection. However, the role of CD103+ TRM was not elucidated in the progress of S. japonicum infection induced disease.Methods: 6-8 weeks old C57BL/6 mice were infected by S. japonicum. Mice were sacrificed and the lungs were removed 5-6 weeks after infection. Immunofluorescent staining and Q-PCR were performed to identify the expression of CD103 molecule. Single cellular populations were made, percentages of CD103 on both CD4+ and CD8+ T lymphocytes were dynamical observed by flow cytometry (FCM). Moreover, the expression of memory T cells related molecules CD69 and CD62L, T cell function associated molecules CD107a, IFN-γ, IL-4, IL-9, and IL-10 were compared between CD103+ CD4+ and CD8+ T cells by FCM.Results: CD103+ cells were emerged in the lung of both naive and S. japonicum infected mice. Both the percentage and the absolute numbers of pulmonary CD4+ and CD8+ cells were increased after S. japonicum infection (P < 0.05). The percentage of CD103+ cells in CD8+ T cells decreased significantly at the early stage of S. japonicum infection (P < 0.05). Increased CD69, decreased CD62L and CD107a expressions were detected on both CD4+ and CD8+ CD103+ T cells in the lungs of infected mice (P < 0.05). Compared to CD8+ CD103+ T cells, CD4+ CD103+ T cells from infected mice expressed higher level of CD69 and lower level CD62L molecules (P < 0.05). Moreover, higher percentage of IL-4+, IL-9+ and IL-10+ cells on CD4+ CD103+ pulmonary T cells was found in infected mice (P < 0.05). Significantly increased IL-4 and IL-9, and decreased IFN-γ expressing cells were detected in CD8+CD103+ cells of infected mice (P < 0.05).Conclusions: CD103-expressing pulmonary CD4+ and CD8+ T cells play important roles in mediating S. japonicum infection induced granulomatous inflammation in the lung. [ABSTRACT FROM AUTHOR]

CD4+ T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in granulomatous responses to Schistosoma japonicum (S. japonicum) infection. However, the role and underlying mechanisms of Tfh cell aggregation in S. japonicum infection remain incompletely understood. In this study, we provide evidence that S. japonicum infection enhances the accumulation of Tfh cells in the spleen, lymph nodes, and peripheral blood of C57BL/6 mice. Infection-induced Tfh cells exhibited more potent effects directly on B cell responses than the control Tfh cells (P < 0.05). Furthermore, reduced apoptosis of Tfh cells was found both in S. japonicum infected mice and in soluble egg antigen (SEA) treated Tfh cells (P < 0.05). Mechanistic studies reveal that caspase-3 is the primary drivers of down-regulated apoptotic Tfh cell death in S. japonicum infection. In summary, this study demonstrates that Tfh cell accumulation might have an impact on the generation of immune responses in S. japonicum infection, and caspase-3 signaling mediated apoptosis down-regulation might responsible for the accumulation of Tfh cell in this course. [ABSTRACT FROM AUTHOR]