Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study.

BACKGROUND: Portal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear. METHODS: 110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt-TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC. RESULTS: The incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI-II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group. CONCLUSION: Compared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.

Evaluation of Molecular Residual Disease by a Fixed Panel in Resectable Colorectal Cancer.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: 75 patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and pre-operative and post-operative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher pre-operative positive rate than the tumor-agnostic assay (73.3% vs 57.3%). The pre-op ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined post-op ctDNA positivity was significantly associated with worse DFS (HR, 20.74, 95%CI 7.19-59.83; p<0.001), which was an independent predictor by multivariable analysis (HR, 28.57, 95%CI 7.10-114.9; p<0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest pre-operative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in post-op landmark (HR, 26.34, 95%CI, 6.01-115.57; p<0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04, 95%CI, 0.94-9.89; p=0.052). Conclusion: Our study confirmed the prognostic value of the ctDNA positivity at post-op day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

PRTA:Joint extraction of medical nested entities and overlapping relation via parameter sharing progressive recognition and targeted assignment decoding scheme.

Nested entities and relationship extraction are two tasks for analysis of electronic medical records. However, most of existing medical information extraction models consider these tasks separately, resulting in a lack of consistency between them. In this paper, we propose a joint medical entity-relation extraction model with progressive recognition and targeted assignment (PRTA). Entities and relations share the information of sequence and word embedding layers in the joint decoding stage. They are trained simultaneously and realize information interaction by updating the shared parameters. Specifically, we design a compound triangle strategy for the nested entity recognition and an adaptive multi-space interactive strategy for relationship extraction. Then, we construct a parameter-shared information space based on semantic continuity to decode entities and relationships. Extensive experiments were conducted on the Private Liver Disease Dataset (PLDD) provided by Beijing Friendship Hospital of Capital Medical University and public datasets (NYT, ACE04 and ACE05). The results show that our method outperforms existing SOTA methods in most indicators, and effectively handles nested entities and overlapping relationships.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation.

OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

DSC-Recon: Dual-Stage Complementary 4D Organ Reconstruction from X-ray Image Sequence for Intraoperative Fusion.

Accurately reconstructing 4D critical organs contributes to the visual guidance in X-ray image-guided interventional operation. Current methods estimate intraoperative dynamic meshes by refining a static initial organ mesh from the semantic information in the single-frame X-ray images. However, these methods fall short of reconstructing an accurate and smooth organ sequence due to the distinct respiratory patterns between the initial mesh and X-ray image. To overcome this limitation, we propose a novel dual-stage complementary 4D organ reconstruction (DSC-Recon) model for recovering dynamic organ meshes by utilizing the preoperative and intraoperative data with different respiratory patterns. DSC-Recon is structured as a dual-stage framework: 1) The first stage focuses on addressing a flexible interpolation network applicable to multiple respiratory patterns, which could generate dynamic shape sequences between any pair of preoperative 3D meshes segmented from CT scans. 2) In the second stage, we present a deformation network to take the generated dynamic shape sequence as the initial prior and explore the discriminate feature (i.e., target organ areas and meaningful motion information) in the intraoperative X-ray images, predicting the deformed mesh by introducing a designed feature mapping pipeline integrated into the initialized shape refinement process. Experiments on simulated and clinical datasets demonstrate the superiority of our method over state-of-the-art methods in both quantitative and qualitative aspects.

Reconstruction of Historical Metal Backgrounds in Lacustrine Environments of China Using an Anodonta woodiana "Specimen Bank".

Anodonta woodiana samples from Xidong Water Works and Mashan in Taihu Lake, Yiyang near Dongting Lake, and Taiping Harbor in Gehu Lake preserved in a "specimen bank" established for the "Freshwater Mussel Watch" monitoring program were used to determine the historical metal backgrounds from different waters in the present study. The elements Co, Ni, Mo, Cd, Al, Cr, Mn, Fe, Cu, Zn, As, Ba, and Pb were determined using A. woodiana from four lacustrine sites. The results showed that Al, Cr, Mn, Fe, Cu, Zn, As, Ba, and Pb were all detected, whereas Co, Ni, Mo, and Cd were below the detection limits of 0.0165, 0.0106, 0.0189 and 0.0182 µg kg- 1, respectively. In particular, A. woodiana was noted to be an unusual Mn hyperaccumulator (ranged from 5124.09 to 13015.47 µg g- 1). The results of discriminant analysis showed that the four water samples could be accurately separated. This difference has the potential to infer the background difference of heavy metal pollution in different lacustrine habitats.

pH-Universal Electrocatalytic CO2 Reduction with Ampere-level Current Density on Doping-engineered Bismuth Sulfide.

The practical application of the electrocatalytic CO2 reduction reaction (CO2RR) to form formic acid fuel is hindered by the limited activation of CO2 molecules and the lack of universal feasibility across different pH levels. Herein, we report a doping-engineered bismuth sulfide pre-catalyst (BiS-1) that S is partially retained after electrochemical reconstruction into metallic Bi for CO2RR to formate/formic acid with ultrahigh performance across a wide pH range. The best BiS-1 maintains a Faraday efficiency (FE) of ~95% at 2000 mA cm-2 in a flow cell under neutral and alkaline solutions. Furthermore, the BiS-1 catalyst shows unprecedentedly high FE (~95%) with current densities from 100 to 1300 mA cm-2 under acidic solutions. Notably, the current density can reach 700 mA cm-2 while maintaining a FE of above 90% in a membrane electrode assembly electrolyzer and operate stably for 150 h at 200 mA cm-2. In-situspectra and density functional theory calculations reveals that the S doping modulates the electronic structure of Bi and effectively promotes the formation of the HCOO* intermediate for formate/formic acid generation. This work develops the efficient and stable electrocatalysts for sustainable formate/formic acid production.

Citric Acid: A Nexus Between Cellular Mechanisms and Biomaterial Innovations.

Citrate-based biodegradable polymers have emerged as a distinctive biomaterial platform with tremendous potential for diverse medical applications. By harnessing their versatile chemistry, these polymers exhibit a wide range of material and bioactive properties, enabling them to regulate cell metabolism and stem cell differentiation through energy metabolism, metabonegenesis, angiogenesis and immunomodulation. Moreover, the recent U.S. Food and Drug Administration (FDA) clearance of the biodegradable poly(octamethylene citrate) (POC)/hydroxyapatite-based orthopedic fixation devices represent a translational research milestone for biomaterial science. POC joins a short list of biodegradable synthetic polymers that have ever been authorized by the FDA for use in humans. The clinical success of POC has sparked enthusiasm and accelerated the development of next-generation citrate-based biomaterials. This review presents a comprehensive, forward-thinking discussion on the pivotal role of citrate chemistry and metabolism in various tissue regeneration and on the development of functional citrate-based metabotissugenic biomaterials for regenerative engineering applications. This article is protected by copyright. All rights reserved.

Mature astrocytes as source for astrocyte repopulation after deletion in the medial prefrontal cortex: Implications for depression.

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.

DEC1 deficiency protects against bone loss induced by ovariectomy through inhibiting inflammation.

Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis (PMOP), we utilized the two types (DEC1 +/+, DEC1 -/-) mice to establish an ovariectomy (OVX) model and found that the bone loss in DEC1 -/- OVX mice were much less than that in DEC1 +/+ OVX mice. The expression levels of RUNX2 and OSX significantly increased in DEC1 -/- OVX mice compared with those in DEC1 +/+ OVX mice. Whereas, NFATc1, c-Fos, CTSK and RANKL/OPG significantly decreased in DEC1 -/- OVX mice compared with those in DEC1 +/+ OVX mice. Likewise, DEC1 deficiency suppressed IL-6 and IL-1ß. Further study showed Runx2, Osx, Alp, and Ocn significantly increased in DEC1 -/- OVX BMSCs compared with those in DEC1 +/+ OVX BMSCs. And the mRNA levels of IL-1ß, IL-6, Tnf-α and Ifn-γ increased significantly in DEC1 +/+ OVX BMMs compared with those in DEC1 +/+ sham BMMs, but not in DEC1 -/- OVX BMMs compared with those in DEC1 -/- sham BMMs. Furthermore, the p-IκBα and p-P65 significantly increased in DEC1 +/+ OVX BMMs compared with those in DEC1 +/+ sham BMMs, but did not increase in DEC1 -/- OVX BMMs compared with those in DEC1 -/- sham BMMs. Taken together, DEC1 deficiency inhibits the NF-κB pathway induced by OVX, thereby decreasing cytokines, and subsequently, inhibits the decrease of osteogenesis and the increase of osteoclastogenesis caused by OVX. The findings provide a novel understanding of postmenopausal osteoporosis development, which offers potential avenues for the intervention strategies.

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

A genome-wide association study of escitalopram treatment outcomes in patients with major depressive disorder.

Major depressive disorder (MDD) is a common psychological condition, the consequences of which, such as suicide, can be severe. Escitalopram, a selective serotonin reuptake inhibitor, is a commonly used antidepressant in clinics. However, more than one-third of patients with MDD do not respond to this drug. Gene polymorphism may affect the efficacy of escitalopram, but the genetic architecture of the antidepressant response in patients with MDD remains unclear. We perform a genome-wide association study (GWAS) of the genetic effect on the outcome of escitalopram in patients with MDD. A total of 203 patients with MDD and 176 healthy control (HC) adults were recruited from Beijing Anding Hospital. Patients received 12 weeks of antidepressant treatment with escitalopram. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Hamilton depression scale (HAMD) were used to evaluate the severity of depression symptoms at the baseline and the end of 2 and 12 weeks of treatment. A total of 140 variants in MDD patients were identified by GWAS to have genome-wide significance (p < 5e - 8) compared with HCs. Similarly, 189 and 18 variants were identified to be associated with QIDS-SR and HAMD score changes in patients after antidepressant treatment (p < 1e - 5), including rs12602361, rs72799048, rs16842235, and rs2518256. In the two weeks QIDS-SR score study, the gene-level association for these variants and gene set enrichment analyses implicate the enrichment of genes involved in the synaptic plasticity process and nervous system development that may be impaired. Our results implicate the predictive capacity of the effect of escitalopram treatment, supporting a link between genetic basis and remission of depression disease.

Additive-Free Anode with High Stability: Nb2CTx MXene Prepared by HCl-LiF Hydrothermal Etching for Lithium-Ion Batteries.

MXenes, represented by Ti3C2Tx, have been widely studied in the electrochemical energy storage fields, including lithium-ion batteries, for their unique two-dimensional structure, tunable surface chemistry, and excellent electrical conductivity. Recently, Nb2CTx, as a new type of MXene, has attracted more and more attention due to its high theoretical specific capacity of 542 mAh g-1. However, the preparation of few-layer Nb2CTx nanosheets with high-quality remains a challenge, which limits their research and application. In this work, high-quality few-layer Nb2CTx nanosheets with a large lateral size and a high conductivity of up to 500 S cm-1 were prepared by a simple HCl-LiF hydrothermal etching method, which is 2 orders of magnitude higher than that of previously reported Nb2CTx. Furthermore, from its aqueous ink, the viscosity-tunable organic few-layer Nb2CTx ink was prepared by HCl-induced flocculation and N-methyl-2-pyrrolidone treatment. When using the organic few-layer Nb2CTx ink as an additive-free anode of lithium-ion batteries, it showed excellent cycling performance with a reversible specific capacity of 524.0 mAh g-1 after 500 cycles at 0.5 A g-1 and 444.0 mAh g-1 after 5000 cycles at 1 A g-1. For rate performance, a specific capacity of 159.8 mAh g-1 was obtained at a high current density of 5 A g-1, and an excellent capacity retention rate of about 95.65% was achieved when the current density returned to 0.5 A g-1. This work presents a simple and scalable process for the preparation of high-quality Nb2CTx and its aqueous/organic ink, which demonstrates important application potential as electrodes for electrochemical energy storage devices.

Bi Nanospheres Embedded in N-Doped Carbon Nanowires Facilitate Ultrafast and Ultrastable Sodium Storage.

Sodium ion batteries (SIBs) are considered as the ideal candidates for the next generation of electrochemical energy storage devices. The major challenges of anode lie in poor cycling stability and the sluggish kinetics attributed to the inherent large Na+ size. In this work, Bi nanosphere encapsulated in N-doped carbon nanowires (Bi@N-C) is assembled by facile electrospinning and carbonization. N-doped carbon mitigates the structure stress/strain during alloying/dealloying, optimizes the ionic/electronic diffusion, and provides fast electron transfer and structural stability. Due to the excellent structure, Bi@N-C shows excellent Na storage performance in SIBs in terms of good cycling stability and rate capacity in half cells and full cells. The fundamental mechanism of the outstanding electrochemical performance of Bi@N-C has been demonstrated through synchrotron in-situ XRD, atomic force microscopy, ex-situ scanning electron microscopy (SEM) and density functional theory (DFT) calculation. Importantly, a deeper understanding of the underlying reasons of the performance improvement is elucidated, which is vital for providing the theoretical basis for application of SIBs.

Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy.

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.

Stepwise Synthesis of Low-Symmetry Hexacationic Pyridinium Organic Cages.

An efficient approach was developed for the synthesis of the well-known BlueCage by pre-bridging two 2,4,6-tris(4-pyridyl)-1,3,5-triazine (TPT) panels with one linker followed by cage formation in a much improved yield and shortened reaction time. Such a stepwise methodology was further applied to synthesize three new pyridinium organic cages, C2, C3, and C4, where the low-symmetry cages C3 and C4 with angled panels demonstrated better recognition properties toward 1,1'-bi-2-naphthol (BINOL) than the high-symmetry analogue C2 featuring parallel platforms.

Divergent Synthesis of Cyclopropanated Tetrahydroquinolines by Tandem Functionalization of Quinoline Derivatives.

Here, reported is a new method for divergent synthesis of functionalized tetrahydroquinolines (THQs), featuring a biomedically interesting azabicyclo[4.1.0]heptane core, proceeding with mild conditions, good substrate and functionality tolerance, and operational simplicity. Mechanistic studies suggest that the products are formed via carbonucleophilic 1,4-addition-induced dearomatization of quinolinium salts and intramolecular cyclopropanation with α-halo ketones followed by α-nucleophilic addition with different nucleophiles. The present work lays a foundation to access new N-heterocycles via the dearomative tandem functionalization of azaarenes.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks.

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.