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Abstract Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent’s concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin’s action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections. Graphical Abstract

Abstract Rechargeable zinc (Zn) batteries have been regarded as a potential alternative for energy storage instrument, but the poor life‐span of Zn metal anodes restrain their commercial application. In this work, stripy Zn array (ZnSA) with preferential (002) crystal plane was designed and fabricated through the facile treatment with concentrated phosphoric acid. The depth of stripy array and the content of (002) plane were controlled through the optimization of etching time. The synergistic effect of stripy morphology and preferential crystal plane can increase the electroactive surface area, suppress the corrosion and hydrogen evolution of aqueous electrolyte, induce the horizontal growth along with basal (002) plane, and inhibit the formation of Zn dendrites. The as‐synthesized ZnSA electrodes can achieve ultra‐long lifespan of 2500 h at the current density of 2 mA cm−2 with a constant capacity of 2 mAh cm−2 and still maintain stable cycling of 1200 and 1400 h even at the higher current density of 10 mA cm−2 and plating/stripping depth of 5 mAh cm−2, respectively. This work proposes a facile and effective strategy to improve electrochemical performance of metallic Zn anodes and contributes to the commercial application of Zn ion batteries.

Abstract Considering the effect of SIRT1 on improving myocardial fibrosis and GAS5 inhibiting occurrence and development of myocardial fibrosis at the cellular level, the aim of the present study was to investigate whether LncRNA GAS5 could attenuate cardiac fibrosis through regulating mir-217/SIRT1, and whether the NLRP3 inflammasome activation was involved in this process. Isoprenaline (ISO) was given subcutaneously to the male C57BL/6 mice to induce myocardial fibrosis and the AAV9 vectors were randomly injected into the left ventricle of each mouse to overexpress GAS5. Primary myocardial fibroblasts (MCFs) derived from neonatal C57BL/6 mice and TGF-β1 were used to induce fibrosis. And the GAS5 overexpressed MCFs were treated with mir-217 mimics and mir-217 inhibitor respectively. Then the assays of expression levels of NLRP3, Caspase-1, IL-1β and SIRT1 were conducted. The findings indicated that the overexpression of GAS5 reduced the expression levels of collagen, NLRP3, Capase-1, IL-1β and SIRT1 in ISO treated mice and TGF-β1 treated MCFs. However, this effect was significantly weakened after mir-217 overexpression, but was further enhanced after knockdown of mir-217. mir-217 down-regulates the expression of SIRT1, leading to increased activation of the NLRP3 inflammasome and subsequent pyroptosis. LncRNA GAS5 alleviates cardiac fibrosis induced via regulating mir-217/SIRT1 pathway.

As a continuation of our previous work on the conservation and breaking of the pseudospin symmetry (PSS) in resonant states [Phys. Lett. B 847, 138320 (2023)], in this work, the PSS in nuclear single-particle bound and resonant states are investigated uniformly within a relativistic framework by exploring the poles of the Green's function in spherical Woods-Saxon potentials. As the potential depths increase from zero to finite depths, the PS partners evolve from resonant states to bound states. In this progress, the PSS is broken gradually with energy, width, and density splittings. Specially, the energy and width splittings for the resonant and bound states are directly determined by the ratio of the pseudo spin-orbit potentials between the PS partners. Obvious threshold effect is observed for the energy splitting at a critical potential depth, with which one PS partner has become a quasi-bound state inside the centrifugal barrier while the other one is still a high-energy resonant state outside the centrifugal barrier. The differences in the density distributions of the lower component between the PS partners are manifested in the phase shift for the resonant states and amplitudes for bound states.

We investigate the equilibrium structure and radial oscillations of strange quark stars admixed with fermionic dark matter. For strange quark matter, we employ a stiff equation of state from a color-superconductivity improved bag model. For dark matter, we adopt the cold free Fermi gas model. We rederive and numerically solve the radial oscillation equations of two-fluid stars based on general relativity, in which the dark matter and strange quark matter couple through gravity and oscillate with the same frequency. Our results show that the stellar maximum mass and radius are reduced by inclusion of dark matter. As to the fundamental mode of the radial oscillations, the frequency f0 is also reduced comparing to pure strange stars, and f02 reaches the zero point at the maximum stellar mass with dM/dϵq,c=0. Therefore, the stability criteria f02>0 and dM/dϵq,c>0 are consistent in our dark matter-mixed strange quark stars with a fixed fraction of dark matter. We also find a discontinuity of f0 as functions of the stellar mass, in contrast to the continuous function in pure strange stars. And it is also accompanied with discontinuity of the oscillation amplitudes as well as a discontinuous in-phase-to-out-phase transition between oscillations of dark matter and strange quark matter.

Pseudospin symmetry (PSS) is a relativistic dynamical symmetry connected with the lower component of the Dirac spinor. Here, we investigate the conservation and breaking of PSS in the single-nucleon resonant states, as an example, using Green's function method that provides a novel way to precisely describe not only the resonant energies and widths but also the spacial density distributions for both narrow and wide resonances. The PSS conservation and breaking are perfectly displayed in the evolution of resonant parameters and density distributions with the potential depth: In the PSS limit, i.e., when the attractive scalar and repulsive vector potentials have the same magnitude but opposite sign, PSS is exactly conserved with strictly the same energy and width between the PS partners as well as identical density distributions of the lower components. As the potential depth increases, the PSS is broken gradually with energy and width splittings and a phase shift in the density distributions.

AbstractObjective To explore potential biomarkers indicating endometriosis (EM).Materials and methods A proteomics method and combined quantitative transcriptomics were adopted to highlight markers in the EM. Venn analysis was used to integrate the ribonucleic acid sequencing (RNA-seq) and protein profiles. Promising candidate markers were tested by enzyme-related immunosorbent assay.Results A sum of 979 mRNAs and 39 proteins were tested to be significantly differentially expression in the standard cluster compared with the EM cluster. Venn analysis showed a filtered signature of only two down-regulated molecules in the EM group, i.e. fetuin B (FETUB) and serpin family C member 1 (SERPINC1); the latter showed a big variance between the control category and the EM set in the authentication test.Conclusion SERPINC1 may be a useful possible biomarker for the analysis of EM.

Neural progenitor cells (NPCs) capable of self-renewal and differentiation into neural cell lineages offer broad prospects for cell therapy for neurodegenerative diseases. However, cell therapy based on NPC transplantation is limited by the inability to acquire sufficient quantities of NPCs. Previous studies have found that a chemical cocktail of valproic acid, CHIR99021, and Repsox (VCR) promotes mouse fibroblasts to differentiate into NPCs under hypoxic conditions. Therefore, we used VCR (0.5 mM valproic acid, 3 μM CHIR99021, and 1 μM Repsox) to induce the reprogramming of rat embryonic fibroblasts into NPCs under a hypoxic condition (5%). These NPCs exhibited typical neurosphere-like structures that can express NPC markers, such as Nestin, SRY-box transcription factor 2, and paired box 6 (Pax6), and could also differentiate into multiple types of functional neurons and astrocytes in vitro. They had similar gene expression profiles to those of rat brain-derived neural stem cells. Subsequently, the chemically-induced NPCs (ciNPCs) were stereotactically transplanted into the substantia nigra of 6-hydroxydopamine-lesioned parkinsonian rats. We found that the ciNPCs exhibited long-term survival, migrated long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Moreover, the parkinsonian behavioral defects of the parkinsonian model rats grafted with ciNPCs showed remarkable functional recovery. These findings suggest that rat fibroblasts can be directly transformed into NPCs using a chemical cocktail of VCR without introducing exogenous factors, which may be an attractive donor material for transplantation therapy for Parkinson’s disease.

The present study systematically analyzed and evaluated the variations in chemical speciation, pollution assessment, and source identification of heavy metals in sediments of Huangpu River. The methods employed included heavy metal concentration, chemical speciation and Cu isotopic compositions analysis. Results showed that the chemical speciation of sediment-bound heavy metals, characterized by significant seasonal variation, shifted from non-residual fractions dominating in spring and summer to residual fractions dominating in autumn and winter. Precipitation was identified as an important factor influencing the chemical speciation of sediment-bound heavy metals. Furthermore, ratio of the secondary phase to the primary phase, RSP (=Cnon-residual/Cresidual) values in Huangpu River sediments were higher than 1 in spring and summer, indicating that sediment-bound heavy metals in Huangpu River were mainly composed of non-residual fractions and could potentially be released into the river water. Principal component analysis (PCA) revealed that navigation, traffic, agricultural, and industrial activities could be the potential sources of heavy metal pollution. Notably, the δ65Cu values in Huangpu River sediments were observed to be isotopically lighter (from −0.37 to +0.18 ‰), suggesting that navigation might be the primary pollution source. These results will not only provide guidance in reducing heavy metal concentrations, but also serve as a crucial basis for policy making regarding heavy metal control.

[INLINE:1] Classic paired associative stimulation can improve synaptic plasticity, as demonstrated by animal experiments and human clinical trials in spinal cord injury patients. Paired associative magnetic stimulation (dual-target peripheral and central magnetic stimulation) has been shown to promote neurologic recovery after stroke. However, it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury. We hypothesize that the current caused by central and peripheral magnetic stimulation will converge at the synapse, which will promote synapse function and improve the motor function of the relevant muscles. Therefore, this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials, motor and sensory function of the lower limbs, functional health and activities of daily living, and depression in patients with spinal cord injury. We will recruit 110 thoracic spinal trauma patients treated in the Department of Spinal Cord Injury, China Rehabilitation Hospital and randomly assign them to experimental and control groups in a 1:1 ratio. The trial group (n = 55) will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment. The control group (n = 55) will be treated with sham stimulation and conventional rehabilitation treatment. Outcomes will be measured at four time points: baseline and 4, 12, and 24 weeks after the start of intervention (active or sham paired associative magnetic stimulation). The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up. Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function score, motor evoked potentials, sensory evoked potentials, modified Ashworth scale score, Maslach Burnout Inventory score, and Hamilton Depression Scale score over time. Motor evoked potential latency reflects corticospinal tract transmission time, while amplitude reflects recruitment ability; both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency. Adverse events will be recorded. Findings from this trial will help to indicate whether paired associative magnetic stimulation (1) promotes recovery of lower limb sensory and motor function, reduces spasticity, and improves quality of life; (2) promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity; and (3) improves rehabilitation outcome in patients with spinal cord injury. Recruitment for this trial began in April 2021 and is currently ongoing. It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University, China (approval No. YZ2020-018) on May 18, 2020. The study protocol was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044794) on March 27, 2021 (protocol version 1.0). This trial will be completed in April 2022.

Ischemia/reperfusion (I/R) injury is a common pathological mechanism involved in many ocular diseases. I/R is characterized by microvascular dysfunction and neurodegeneration. However, the mechanisms of neurodegeneration induced by I/R remain largely unknown. This study showed that the expression of long non-coding RNA-CRNDE was significantly upregulated after retinal ischemia-reperfusion (RIR). LncRNA-CRNDE knockdown alleviated retinal neurodegeneration induced by RIR injury, as shown by decreased reactive gliosis and reduced retinal cells loss. Furthermore, lncRNA-CRNDE knockdown directly regulated Müller cell function and indirectly affected RGC function in vitro. In addition, lncRNA-CRNDE knockdown led to a significant reduction in the release of several cytokines after RIR. This study suggests that lncRNA-CRNDE is a promising therapeutic target for RIR.

Based on an equivparticle model, we investigate the in-medium quark condensate in neutron stars. Carrying out a Taylor expansion of the nuclear binding energy to the order of ρ3, we obtain a series of EOSs for neutron star matter, which are confronted with the latest nuclear and astrophysical constraints. The in-medium quark condensate is then extracted from the constrained properties of neutron star matter, which decreases non-linearly with density. However, the chiral symmetry is only partially restored with non-vanishing quark condensates, which may vanish at a density that is out of reach for neutron stars.

Abstract Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.