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1.
Adv Healthc Mater ; : e2400091, 2024 May 09.
Article En | MEDLINE | ID: mdl-38722148

The role of the biomechanical stimulation generated from soft tissue has not been well quantified or separated from the self-regulated hard tissue remodeling governed by Wolff's Law. Prosthodontic overdentures, commonly used to restore masticatory functions, can cause localized ischemia and inflammation as they often compress patients' oral mucosa and impede local circulation. This biomechanical stimulus in mucosa is found to accelerate the self-regulated residual ridge resorption (RRR), posing ongoing clinical challenges. Based on the dedicated long-term clinical datasets, we developed an in-silico framework with a combination of techniques, including advanced image post-processing, patient-specific finite element models and unsupervised machine learning Self-Organizing map algorithm, to identify the soft tissue induced residual ridge resorption and quantitatively elucidate the governing relationship between the RRR and hydrostatic pressure in mucosa. The proposed governing equation has not only enabled a predictive simulation for RRR as showcased in this study, providing a biomechanical basis for optimizing prosthodontic treatments, but also extended our understanding of the mechanobiological responses in the soft-hard tissue interfaces and the role in bone remodeling. This article is protected by copyright. All rights reserved.

2.
Ann Clin Microbiol Antimicrob ; 23(1): 40, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702782

BACKGROUND: Pretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug. METHODS: To investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020. RESULTS: We observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2-4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes. CONCLUSIONS: Our results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.


Antitubercular Agents , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Humans , Antitubercular Agents/pharmacology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/epidemiology , Prevalence , Nitroimidazoles/pharmacology , Genotype , Mutation , Whole Genome Sequencing
3.
Health Sci Rep ; 7(5): e2069, 2024 May.
Article En | MEDLINE | ID: mdl-38706804

Background and Aims: The effectiveness of immune checkpoint inhibitors (ICIs) in low programmed death ligand 1 (PD-L1) expression in cervical cancer (CC) patients remains unknown. We aimed to evaluate the efficacy of ICIs in low PD-L1 expression CC patients. Methods: The study is an individual patient data (IPD)-based meta-analysis. IPD were compiled through KMSubtraction and IPDfromKM methodologies from high-quality randomized clinical trials and single-arm studies which reported overall survival (OS) or progression-free survival (PFS) stratified by PD-L1 expression. Kaplan-Meier curves and Cox regression analysis were employed to evaluate the survival benefits of ICIs. Results: A total of eight studies and 1110 cases were included in the analysis. Within the low PD-L1 expression subgroup, ICI combination therapy, but not ICI monotherapy, demonstrated significant OS benefits over non-ICI treatment (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.36-1.04, p = 0.06). Concerning PFS, ICI monotherapy was associated with a negative effect compared to non-ICI treatment (HR = 4.59, 95% CI: 2.32-9.07, p < 0.001). Notably, both OS and PFS outcomes were unfavorable for ICI monotherapy compared to both non-ICI and ICI combination therapy in the combined positive score <1 subgroup (OS: HR = 2.60, 95% CI: 1.31-5.16, p = 0.008; PFS: HR = 7.59, 95% CI: 3.53-16.31, p < 0.001). Conclusion: In patients with CC and low PD-L1 expression, ICI monotherapy may not be considered as the optimal treatment strategy when compared to non-ICI treatment or ICI combination therapy. Registration: CRD42023395103.

4.
J Inflamm Res ; 17: 2697-2710, 2024.
Article En | MEDLINE | ID: mdl-38707955

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

5.
Front Genet ; 15: 1365285, 2024.
Article En | MEDLINE | ID: mdl-38689653

Hypoxia is a mounting problem that affects the world's freshwaters, with severe consequence for many species, including death and large economical loss. The hypoxia problem has increased recently due to the combined effects of water eutrophication and global warming. In this study, we investigated the transcriptome atlas for the bony fish Ancherythroculter nigrocauda under hypoxia for 1.5, 3, and 4.5 h and its recovery to normal oxygen levels in heart and brain tissues. We sequenced 21 samples for brain and heart tissues (a total of 42 samples) plus three control samples and obtained an average of 32.40 million raw reads per sample, and 95.24% mapping rate of the filtered clean reads. This robust transcriptome dataset facilitated the discovery of 52,428 new transcripts and 6,609 novel genes. In the heart tissue, the KEGG enrichment analysis showed that genes linked to the Vascular smooth muscle contraction and MAPK and VEGF signaling pathways were notably altered under hypoxia. Re-oxygenation introduced changes in genes associated with abiotic stimulus response and stress regulation. In the heart tissue, weighted gene co-expression network analysis pinpointed a module enriched in insulin receptor pathways that was correlated with hypoxia. Conversely, in the brain tissue, the response to hypoxia was characterized by alterations in the PPAR signaling pathway, and re-oxygenation influenced the mTOR and FoxO signaling pathways. Alternative splicing analysis identified an average of 27,226 and 28,290 events in the heart and brain tissues, respectively, with differential events between control and hypoxia-stressed groups. This study offers a holistic view of transcriptomic adaptations in A. nigrocauda heart and brain tissues under oxygen stress and emphasizes the role of gene expression and alternative splicing in the response mechanisms.

6.
Front Neurol ; 15: 1296758, 2024.
Article En | MEDLINE | ID: mdl-38689882

Objective: To evaluate the clinical effectiveness of combining postural control with electroacupuncture in the treatment of dysphagia following stroke, with the goal of establishing a solid clinical foundation for this therapeutic approach and investigating potential mechanisms to stimulate additional research and progress in post-stroke dysphagia management. Methods: 138 patients who met the diagnostic and inclusion criteria were enrolled and divided into control group and observation group. Both groups received conventional rehabilitation training. Additionally, the control group received swallowing training and diet optimize, while the observation group received swallowing training, diet optimize, posture control as well as electroacupuncture therapy. After four weeks, swallowing function was assessed and compared between the two groups using the Standardized Swallowing Assessment (SSA) score and water swallowing test (WST). Results: Patients who underwent postural control therapy in combination with electroacupuncture demonstrated significantly higher treatment efficacy compared to the control group. Notably, The SSA score and WST score in both groups decreased significantly, and the observation group showed more improvements in aspiration compared to the control group. Conclusion: The integration of posture control, electroacupuncture, and conventional rehabilitation training can effectively lower the degree of post-stroke swallowing disorders, restore swallowing function, and significantly reduce the occurrence of complications such as aspiration, fever, and nutritional disorders. Moreover, this approach significantly improves the quality of life of patients and is more effective than conventional rehabilitation training in treating post-stroke swallowing disorders. Clinical trial registration: https://www.chictr.org.cn/, Identifier ChiCTR2300075870.

7.
Inorg Chem ; 2024 May 01.
Article En | MEDLINE | ID: mdl-38691448

Potocatalytic hydrogen evolution represnets a promising way to achieve renewable energy sources. Dual heterojunctions with an inverse opal structure are proposed for addressing fundamental challenges (low surface area, inefficient light absorption, and poor charge separation) in photocatalytic water splitting. Inverse opal structure and Co3O4 were introduced to design and synthesize a ZnO/ZnS/Co3O4 (IO-ZnO/ZnS/Co3O4) photocatalyst. Morphology characterizations and photoelectric measurements reveal that the introduction of three-dimensional (3D) structures and dual heterojunctions improves light utilization efficiency and accelerates charge separation, greatly promoting photoelectric performance. The as-prepared IO-ZnO/ZnS/Co3O4 manifests superior photocurrent density (0.49 mA/cm2), which is 4 times higher than that of IO-ZnO/ZnS due to the existence of dual heterojunctions. The result is further confirmed by an enhanced H2 production rate (153.01 µmol/g/h) in pure water. Notably, excellent cycling stability is achieved in pure water because Co3O4 can rapidly capture photogenerated holes to inhibit severe photocorrosion of ZnO/ZnS. Therefore, this work presents a new insight into inhibiting photocorrosion of metal sulfides and promoting their photoelectric performance by combining 3D structures and dual heterojunctions.

8.
Adv Healthc Mater ; : e2400760, 2024 May 04.
Article En | MEDLINE | ID: mdl-38703026

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

9.
Cancer Lett ; : 216935, 2024 May 02.
Article En | MEDLINE | ID: mdl-38704136

Hepatocellular carcinoma (HCC) is a prevalent malignancy characterized by complex heterogeneity and drug resistance. Resistance to ferroptosis is closely related to the progression of HCC. While HCC tumors vary in their sensitivity to ferroptosis, the precise factors underlying this heterogeneity remain unclear. In this study, we sought to elucidate the mechanisms that contribute to ferroptosis resistance in HCC. Whole-genome CRISPR/Cas9 screen using a subtoxic concentration (IC20) of ferroptosis inducer erastin in the HCC cell line Huh7 revealed TRIM34 as a critical driver of ferroptosis resistance in HCC. Further investigation revealed that TRIM34 suppresses ferroptosis in HCC cells, promoting their proliferation, migration, and invasion both in vitro and in vivo. Furthermore, TRIM34 expression is elevated in HCC tumor tissues, correlating with a poor prognosis. Mechanistically, TRIM34 directly interacts with Up-frameshift 1 (UPF1), a core component of the nonsense-mediated mRNA decay (NMD) pathway, to promote its ubiquitination and degradation. This interaction suppresses GPX4 transcript degradation, thus promoting the protein levels of this critical ferroptosis suppressor in HCC. In light of the close crosstalk between ferroptosis and the adaptive immune response in cancer, HCC cells with targeting knockdown of TRIM34 exhibited an improved response to anti-PD-1 treatment. Taken together, the TRIM34/UPF1/GPX4 axis mediates ferroptosis resistance in HCC, thereby promoting malignant phenotypes. Targeting TRIM34 may thus represent a promising new strategy for HCC treatment.

10.
PLoS One ; 19(5): e0301484, 2024.
Article En | MEDLINE | ID: mdl-38696398

BACKGROUND AND STUDY AIM: The klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones. METHODS: Data was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones. RESULTS: In the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all P<0.01) and negatively correlated with TSH, tT4/tT3, and fT4/fT3 (all P<0.05). Furthermore, tT3, tT4, fT3and tT3/fT3 (P < 0.05) were still significant in the adjusted model. And it is worth noting that there is an approximately L-shaped nonlinear relationship between ln(klotho) and fT3,tT3 with a cut-off point of 6.697 (P-non-linear < 0.05). The stratification analysis showed gender and iodine level differences in the relationship between serum Klotho levels and thyroid hormones. CONCLUSION: There is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.


Glucuronidase , Klotho Proteins , Thyroid Hormones , Humans , Male , Female , Glucuronidase/blood , Cross-Sectional Studies , Thyroid Hormones/blood , Middle Aged , Adult , Aged
11.
Article En | MEDLINE | ID: mdl-38695344

BACKGROUND AND AIM: The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi-society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. METHOD: We conducted a population-based cross-sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. RESULTS: A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non-MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA-IR (adjusted OR: 1.33, 95% CI: 1.10-2.03) was associated with higher risk of moderate-to-severe steatosis for MASLD non-MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations. CONCLUSION: Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.

12.
Article En | MEDLINE | ID: mdl-38696011

Water contamination by hexavalent chromium (Cr(VI)) seriously jeopardizes human health, which is a pressing environmental concern. Biochar-loaded green-synthesized nZVI, as a green and environmentally friendly material, can efficiently reduce Cr(VI) to Cr(III) while removing Cr(VI) from water. Therefore, in this study, an efficient green-modified biochar material (TP-nZVI/BC) was successfully prepared using tea polyphenol (TP) and sludge biochar (BC) using a low-cost and environmentally friendly green synthesis method. The preparation conditions of TP-nZVI/BC were optimized using response surface methodology (RSM), revealing that the dosage of tea polyphenols plays a crucial role in the removal performance (R2 = 1271.09), followed by reaction time and temperature. The quadratic regression model proved accurate. The optimal preparation conditions are as follows: tea polyphenols (TP) dosage at 48 g/L, reaction temperature at 75 ℃, and a reaction time of 3 h. TP-nZVI/BC removed Cr(VI) from water at a rate 7.6 times greater than BC. The pseudo-second-order kinetic model (R2 = 0.987) accurately describes the adsorption process, suggesting that chemical adsorption predominantly controls the removal process. The adsorption of Cr(VI) by TP-nZVI/BC can be well described by the Langmuir model, and the maximum adsorption capacity reached 105.65 mg/g. FTIR and XPS analyses before and after adsorption demonstrate that nZVI plays a crucial role in the reduction process of Cr(VI), and the synergistic effects of surface adsorption, reduction, and co-precipitation enhance Cr(VI) removal. In summary, using green-modified biochar for Cr(VI) removal is a feasible and promising method with significant potential.

13.
JCI Insight ; 9(9)2024 May 08.
Article En | MEDLINE | ID: mdl-38716726

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope protein 1 (SYNE1), a cardiovascular candidate gene, in 3 of 16 families with early-onset COEH without an antecedent family history. By leveraging exome sequence data from an additional 48 COEH families, 1,700 in-house trios, and publicly available data sets, we demonstrate that compound heterozygous SYNE1 variation in these COEH individuals occurred more often than expected by chance and that this class of biallelic rare variation was significantly enriched among individuals of African genetic ancestry. Using in vitro shRNA knockdown of SYNE1, we show that reduced SYNE1 expression resulted in a substantial decrease in the elasticity of smooth muscle vascular cells that could be rescued by pharmacological inhibition of the downstream RhoA/Rho-associated protein kinase pathway. These results provide insights into the molecular genetics and underlying pathophysiology of COEH and suggest a role for precision therapeutics in the future.


Cytoskeletal Proteins , Essential Hypertension , Exome Sequencing , Nerve Tissue Proteins , Adolescent , Child , Female , Humans , Male , Age of Onset , Cytoskeletal Proteins/genetics , Essential Hypertension/genetics , Exome/genetics , Genetic Predisposition to Disease , Mutation, Missense/genetics , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Pedigree , rhoA GTP-Binding Protein/genetics , United States/epidemiology , Infant, Newborn , Infant , Child, Preschool , Young Adult
14.
BMJ Open ; 14(5): e081940, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719309

OBJECTIVES: This study aimed to determine the potential profiles of self-psychological adjustment in patients with lung cancer undergoing chemotherapy, including sense of coherence (SOC) and positive cognitive emotion regulation (PCER). The relationship between these profiles with post-traumatic growth (PTG) and the relevant factors of self-psychological adjustment in different profiles was analysed. DESIGN: Cross-sectional study. SETTING: Patients with lung cancer undergoing chemotherapy in China. PARTICIPANTS: A total of 330 patients with lung cancer undergoing chemotherapy were recruited out of which 321 completed the questionnaires effectively. METHODS: Latent profile analysis was used to identify self-psychological adjustment classes based on the two subscales of the Sense of Coherence Scale and Cognitive Emotion Regulation Questionnaire. One-way analysis of variance and multinomial logistic regression were performed to examine the subgroup association with characteristics and PTG. RESULTS: Three latent profiles of self-psychological adjustment were identified: low level (54.5%), high SOC-low PCER (15.6%) and high PCER (29.9%). The results of univariate analysis showed a significant difference in PTG scores among different self-psychological adjustment subgroups (F=11.55, p<0.001). Patients in the high-PCER group were more likely living in urban areas (OR=2.41, 95% CI 1.17 to 4.97, p=0.02), and time since cancer diagnosis was ≥6 months and <1 year (OR=3.54, 95% CI 1.3 to 9.64, p<0.001). CONCLUSION: This study revealed that most patients with lung cancer undergoing chemotherapy belonged to the low-level group. Three profiles are associated with PTG. There were differences in characteristics between patients treated with chemotherapy for lung cancer in the high-PCER and low-PCER groups. Thus, these profiles provide useful information for developing targeted individualised interventions based on demographic characteristics that would assist PTG in patients with lung cancer undergoing chemotherapy.


Lung Neoplasms , Posttraumatic Growth, Psychological , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/psychology , Male , Cross-Sectional Studies , Female , Middle Aged , China/epidemiology , Aged , Adaptation, Psychological , Sense of Coherence , Surveys and Questionnaires , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Adult , Emotional Adjustment
15.
Toxicol Appl Pharmacol ; 486: 116951, 2024 May 03.
Article En | MEDLINE | ID: mdl-38705401

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

16.
ACS Biomater Sci Eng ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38696332

The present work describes a preclinical trial (in silico, in vivo and in vitro) protocol to assess the biomechanical performance and osteogenic capability of 3D-printed polymeric scaffolds implants used to repair partial defects in a sheep mandible. The protocol spans multiple steps of the medical device development pipeline, including initial concept design of the scaffold implant, digital twin in silico finite element modeling, manufacturing of the device prototype, in vivo device implantation, and in vitro laboratory mechanical testing. First, a patient-specific one-body scaffold implant used for reconstructing a critical-sized defect along the lower border of the sheep mandible ramus was designed using on computed-tomographic (CT) imagery and computer-aided design software. Next, the biomechanical performance of the implant was predicted numerically by simulating physiological load conditions in a digital twin in silico finite element model of the sheep mandible. This allowed for possible redesigning of the implant prior to commencing in vivo experimentation. Then, two types of polymeric biomaterials were used to manufacture the mandibular scaffold implants: poly ether ether ketone (PEEK) and poly ether ketone (PEK) printed with fused deposition modeling (FDM) and selective laser sintering (SLS), respectively. Then, after being implanted for 13 weeks in vivo, the implant and surrounding bone tissue was harvested and microCT scanned to visualize and quantify neo-tissue formation in the porous space of the scaffold. Finally, the implant and local bone tissue was assessed by in vitro laboratory mechanical testing to quantify the osteointegration. The protocol consists of six component procedures: (i) scaffold design and finite element analysis to predict its biomechanical response, (ii) scaffold fabrication with FDM and SLS 3D printing, (iii) surface treatment of the scaffold with plasma immersion ion implantation (PIII) techniques, (iv) ovine mandibular implantation, (v) postoperative sheep recovery, euthanasia, and harvesting of the scaffold and surrounding host bone, microCT scanning, and (vi) in vitro laboratory mechanical tests of the harvested scaffolds. The results of microCT imagery and 3-point mechanical bend testing demonstrate that PIII-SLS-PEK is a promising biomaterial for the manufacturing of scaffold implants to enhance the bone-scaffold contact and bone ingrowth in porous scaffold implants. MicroCT images of the harvested implant and surrounding bone tissue showed encouraging new bone growth at the scaffold-bone interface and inside the porous network of the lattice structure of the SLS-PEK scaffolds.

17.
Front Plant Sci ; 15: 1367299, 2024.
Article En | MEDLINE | ID: mdl-38716337

Angelica dahurica is a kind of Chinese traditional herbs with economic and ornament value, widely distributed in China. Despite its significance, there have been limited comprehensive investigations on the genome of A. dahurica, particularly regarding mitochondrial genomes. To investigate the conversion between mitochondrial genome and chloroplast genome, a complete and circular mitochondrial genome was assembled using Oxford Nanopore Technologies (ONT) long reads. The mitochondrial genome of A. dahurica had a length of 228,315 base pairs (bp) with 45.06% GC content. The mitochondrial genome encodes 56 genes, including 34 protein-coding genes, 19 tRNA genes and 3 rRNA genes. Moreover, we discovered that 9 homologous large fragments between chloroplast genome and mitochondrial genome based on sequence similarity. This is the first report for A. dahurica mitochondrial genome, which could provide an insight for communication between plastid genome, and also give a reference genome for medicinal plants within the Angelica family.

18.
J Infect Dis ; 2024 May 08.
Article En | MEDLINE | ID: mdl-38718217

BACKGROUND: The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among U.S. adults with and without HIV-1 infection is not well-characterized in the conjugate vaccine era. METHODS: We determined Spn colonization frequency by culture and specific lytA gene QPCR and microbiota profile by 16S rRNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics. RESULTS: The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; p=0.46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (i.e., beta-diversity. NP: p=0.0028, OP: p=0.0098), decreased alpha-diversity (NP: p=0.024, OP: p=0.0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered beta-diversity in the NP (p=0.011), but not OP (p=0.21). CONCLUSIONS: Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the pre-conjugate era. The persistently increased risk of pneumococcal disease despite ART may relate to behavioral and immunologic variables other than colonization.

19.
Light Sci Appl ; 13(1): 110, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724516

Entanglement plays a vital role in quantum information processing. Owing to its unique material properties, silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities. To date, however, only entanglement of nuclear spins has been reported in silicon carbide, while an entangled photon source, whether it is based on bulk or chip-scale technologies, has remained elusive. Here, we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time. Specifically, strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform. The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW, corresponding to a pair generation rate of (9 ± 1) × 103 pairs/s. Energy-time entanglement is created and verified for such signal-idler photon pairs, with the two-photon interference fringes exhibiting a visibility larger than 99%. The heralded single-photon properties are also measured, with the heralded g(2)(0) on the order of 10-3, demonstrating the SiC platform as a prospective fully integrated, complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.

20.
Environ Sci Technol ; 58(15): 6736-6743, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38564367

Acidity is an important property of particulate matter (PM) in the atmosphere, but its association with PM toxicity remains unclear. Here, this study quantitively reports the effect of the acidity level on PM toxicity via pH-control experiments and cellular analysis. Oxidative stress and cytotoxicity potencies of acidified PM samples at pH of 1-2 were up to 2.8-5.2 and 2.1-13.2 times higher than those at pH of 8-11, respectively. The toxic potencies of PM samples from real-world smoke plumes at the pH of 2.3 were 9.1-18.2 times greater than those at the pH of 5.6, demonstrating a trend similar to that of acidified PM samples. Furthermore, the impact of acidity on PM toxicity was manifested by promoting metal dissolution. The dramatic increase by 2-3 orders of magnitude in water-soluble metal content dominated the variation in PM toxicity. The significant correlation between sulfate, the pH value, water-soluble Fe, IC20, and EC1.5 (p < 0.05) suggested that acidic sulfate could enhance toxic potencies by dissolving insoluble metals. The findings uncover the superficial association between sulfate and adverse health outcomes in epidemiological research and highlight the control of wet smoke plume emissions to mitigate the toxicity effects of acidity.


Air Pollutants , Particulate Matter , Particulate Matter/analysis , Air Pollutants/toxicity , Air Pollutants/analysis , Metals/toxicity , Metals/analysis , Smoke/analysis , Sulfates/analysis , Water , Environmental Monitoring
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