Nanomedicine-based disulfiram and metal ion co-delivery strategies for cancer treatment.

Disulfiram (DSF) is a second-line drug for the clinical treatment of alcoholism and has long been proven to be safe for use in clinical practice. In recent years, researchers have discovered the cancer-killing activity of DSF, which is highly dependent on the presence of metal ions, particularly copper ions. Additionally, free DSF is highly unstable and easily degraded within few minutes in blood circulation. Therefore, an ideal DSF formulation should facilitate the co-delivery of metal ions and safeguard the DSF throughout its biological journey before reaching the targeted site. Extensive research have proved that nanotechnology based formulations can effectively realize this goal by strategic encapsulation therapeutic agents within nanoparticle. To be more specific, this is accomplished through precise delivery, coordinated release of metal ions at the tumor site, thereby amplifying its cytotoxic potential. Beyond traditional co-loading techniques, innovative approaches such as DSF-metal complex and metal nanomaterials, have also demonstrated promising results at the animal model stage. This review aims to elucidate the anticancer mechanism associated with DSF and its reliance on metal ions, as well as to provide a comprehensive overview of recent advances in the arena of nanomedicine based co-delivery strategies for DSF and metal ion in the context of cancer therapy.

An In Vitro Evaluation of the Effect of Bifidobacterium longum L556 on Microbiota Composition and Metabolic Properties in Patients with Coronary Heart Disease (CHD).

Bifidobacterium longum (B. longum) is a beneficial anaerobic bacteria that may improve cardiovascular disease (CVD). We studied B. longum L556, isolated from healthy human feces, in coronary heart disease (CHD) patients through anaerobic fermentation in vitro. Results showed that B. longum L556 increased Lactobacillus, Faecalibacterium, Prevotella, and Alistipes, while reducing Firmicutes to Bacteroidetes, Eggerthella, Veillonella, Holdemanella, and Erysipelotrichaceae_UCG-003 in the gut microbiota of CHD patients. B. longum L556 also enhanced anti-inflammatory effects by modulating gut microbiota and metabolites like SCFAs. Additionally, it regulated lipid and amino acid metabolism in fermentation metabolites from the CHD group. These findings suggest that B. longum L556 has potential for improving CHD by modulating the intestinal microbiota, promoting SCFA production, and regulating lipid metabolism and inflammation.

SP2509, a specific antagonist of LSD1, exhibits antiviral properties against Porcine epidemic diarrhea virus.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a type of coronavirus, is one of the main pathogens that can infect pigs of all ages. It causes diarrhea and acute death of newborn piglets, resulting in massive economic losses to the worldwide swine industry. While vaccination remains the primary approach in combating PEDV, it often fails to address all the challenges posed by the infection, particularly in light of the emergence of evolving mutant strains. Therefore, there is a critical need to identify potent antiviral drugs that can effectively safeguard pigs against PEDV infection. RESULTS: In this study, the antiviral efficacy of SP2509, a specific antagonist of Lysine-specific demethylase 1(LSD1), was evaluated in vitro. The RT-qPCR, Western blot, TCID50, and IFA showed that at a concentration of 1µmol/L, SP2509 significantly inhibited PEDV infection. Additionally, viral life cycle assays showed that SP2509 operates by impeding PEDV internalization and replication rather than attachment and release. Regarding mechanism, in Huh-7 cells, knockdowns LSD1 can suppress PEDV replication. This indicated that the inhibition effect of SP2509 on PEDV largely depends on the activity of its target protein, LSD1. CONCLUSION: Our results in vitro show that SP2509 can inhibit PEDV infection during the internalization and replication stage and revealed a role of LSD1 as a restriction factor for PEDV. These imply that LSD1 might be a target for interfering with the viral infection, and SP2509 could be developed as an effective anti-PEDV agent.

Risk factors and metabolomics of mild cognitive impairment in type 2 diabetes mellitus.

Objective: This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers. Results: Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group (p < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency. Conclusion: This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.

Norepinephrine may promote the progression of Fusobacterium nucleatum related colorectal cancer via quorum sensing signalling.

Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of ApcMin/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.

Circumvention of Topoisomerase IIα Intron 19 Intronic Polyadenylation (IPA) in Acquired Etoposide Resistant Human Leukemia K562 Cells.

DNA topoisomerase IIα (TOP2α, 170kDa, TOP2α/170) is an essential enzyme for proper chromosome dysjunction by producing transient DNA double-stranded breaks and is a significant target for DNA damage stabilizing anti-cancer agents such as etoposide. Therapeutic effects of TOP2α poisons can be limited due to acquired drug resistance. We previously demonstrated decreased TOP2α/170 levels in an etoposide-resistant human leukemia K562 subline, designated K/VP.5, accompanied by increased expression of a C-terminal truncated TOP2α isoform (90 kDa, TOP2α/90) which heterodimerized with TOP2α/170 and was a determinant of resistance by exhibiting dominant-negative effects against etoposide activity. Based on 3'-Rapid Amplification of cDNA Ends (3'-RACE), we confirmed TOP2α/90 as the translation product of a TOP2α mRNA in which a cryptic polyadenylation site (PAS) harbored in intron 19 (I19) was utilized. We hypothesized that resultant intronic polyadenylation (IPA) can would be attenuated by blocking or mutating the I19 PAS thereby circumventing acquired drug resistance. An antisense morpholino oligonucleotide (AMO) was used to hybridize/block the PAS in TOP2α pre-mRNA in K/VP.5 cells, resulting in decreased TOP2α/90 mRNA/protein levels in K/VP.5 cells and partially circumventing drug resistance. Subsequently, CRISPR/Cas9 homology-directed repair (HDR) was used to mutate the cryptic I19 PAS (AATAAA-->ACCCAA) to prevent IPA. Gene-edited clones exhibited increased TOP2α/170 and decreased TOP2α/90 mRNA/protein and demonstrated restored sensitivity to etoposide and other TOP2α-targeted drugs. Together, results indicated that blocking/mutating a cryptic I19 PAS in K/VP.5 cells reduced IPA and restored sensitivity to TOP2α-targeting drugs. Significance Statement Results presented here indicate that CRISPR/Cas9 gene editing of a cryptic polyadenylation site (PAS) within I19 of the TOP2α gene results in reversal of acquired resistance to etoposide and other TOP2-targeted drugs. An antisense morpholino oligonucleotide (AMO) targeting the PAS also partially circumvented resistance. Results demonstrate the importance of intronic polyadenylation (IPA) in acquired drug resistance and points to tractable strategies to overcome this form of resistance to TOP2-targeted agents.

Superfast Zincophilic Ion Conductor Enables Rapid Interfacial Desolvation Kinetics for Low-Temperature Zinc Metal Batteries.

Low-temperature rechargeable aqueous zinc metal batteries (AZMBs) as highly promising candidates for energy storage are largely hindered by huge desolvation energy barriers and depressive Zn2+ migration kinetics. In this work, a superfast zincophilic ion conductor of layered zinc silicate nanosheet (LZS) is constructed on a metallic Zn surface, as an artificial layer and ion diffusion accelerator. The experimental and simulation results reveal the zincophilic ability and layer structure of LZS not only promote the desolvation kinetics of [Zn(H2O)6]2+ but also accelerate the Zn2+ transport kinetics across the anode/electrolyte interface, guiding uniform Zn deposition. Benefiting from these features, the LZS-modified Zn anodes showcase long-time stability (over 3300 h) and high Coulombic efficiency with ≈99.8% at 2 mA cm-2, respectively. Even reducing the environment temperature down to 0 °C, ultralong cycling stability up to 3600 h and a distinguished rate performance are realized. Consequently, the assembled Zn@LZS//V2O5-x full cells deliver superior cyclic stability (344.5 mAh g-1 after 200 cycles at 1 A g-1) and rate capability (285.3 mAh g-1 at 10 A g-1) together with a low self-discharge rate, highlighting the bright future of low-temperature AZMBs.

Hollow UiO-66-NH2 encapsulated Pd catalysts for highly selective hydrogenation of furfural to furfuryl alcohol.

The selective hydrogenation of furfural (FFA) to furfuryl alcohol (FA) is regarded as attractive transformation to achieve the sustainable synthesis of value-added chemicals from biomass resources. However, the conventional supported catalysts are significantly restricted by their narrow pore size, ununiform dispersion and easy leaching or aggregation of catalytic sites. Herein, we designed hollow UiO-66-NH2 as the support to encapsulate Pd nanoparticles (Pd@H-UiO-66-NH2) to achieve the highly active and selective conversion of FFA to FA. Benefiting from the void-confinement effect and substrate enrichment of hollow structure, as well as the surface wrinkles, the as-prepared catalyst Pd@H-UiO-66-NH2 exhibited 96.8 % conversion of FFA with satisfactory selectivity reaching up to 92.4 % at 80 °C, 0.5 MPa H2 in isopropanol solvent within 6 h. More importantly, as-prepared Pd@H-UiO-66-NH2 catalyst exhibited excellent long-term stability, as well as good universality toward a series of hydrogenation of unsaturated hydrocarbons.

Serum uric acid is associated with midbrain enlarged perivascular spaces: Results from Multi-modality Medical imaging sTudy bAsed on KaiLuan Study (META-KLS).

BACKGROUND: Serum uric acid (SUA) is a major cause of cardiovascular and cerebrovascular diseases. Whether and to what extent the excess risk of enlarged perivascular spaces (EPVS) conferred by SUA is unknown. The study was conducted to investigate the association between SUA and EPVS in different brain regions. METHODS: Data are from Multi-modality medical imaging study based on Kailuan study (META-KLS) in this cross-sectional study. Participants were divided into five groups based on SUA levels, and EPVS in basal ganglia (BG), centrum semiovale (CSO) and midbrain (MB) was systematically assessed and divided into Low and High group. Odds ratio (OR) and 95% confidence intervals (95% CIs) for high EPVS outcomes were estimated using multivariable logistic regression analysis. Restricted cubic spline (RCS) was used to further investigate dose-response relationship. RESULTS: A total of 1014 participants aged 25-83 years from 11 centers were enrolled in the study. In the multivariable-adjusted model, SUA, as an independent risk factor, correlated positively with high degree of MB-EPVS (OR, 1.002; 95% CI, 1.000 to 1.004; p = 0.023) in general population. In addition, RCS further demonstrated the linear association between SUA and MB-EPVS (p = 0.072). No association was found between SUA and BG-EPVS or CSO-EPVS. CONCLUSION: SUA was an independent risk factor of MB-EPVS. High SUA levels were more predictive of increased risk occurrence of high degree of MB-EPVS, supporting a linear association between SUA and MB-EPVS and further indicating that SUA may play an important role in cerebral small vessel disease. TRIAL REGISTRATION: The KaiLuan Study and META-KLS were registered online (ChiCTR2000029767 on chictr.org.cn and NCT05453877 on Clinicaltrials.gov, respectively).

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Bioreduction of chromate in a syngas-based membrane biofilm reactor.

This study leveraged synthesis gas (syngas), a renewable resource attainable through the gasification of biowaste, to achieve efficient chromate removal from water. To enhance syngas transfer efficiency, a membrane biofilm reactor (MBfR) was employed. Long-term reactor operation showed a stable and high-level chromate removal efficiency > 95%, yielding harmless Cr(III) precipitates, as visualised by scanning electron microscopy and energy dispersive X-ray analysis. Corresponding to the short hydraulic retention time of 0.25 days, a high chromate removal rate of 80 µmol/L/d was attained. In addition to chromate reduction, in situ production of volatile fatty acids (VFAs) by gas fermentation was observed. Three sets of in situ batch tests and two groups of ex situ batch tests jointly unravelled the mechanisms, showing that biological chromate reduction was primarily driven by VFAs produced from in situ syngas fermentation, whereas hydrogen originally present in the syngas played a minor role. 16 S rRNA gene amplicon sequencing has confirmed the enrichment of syngas-fermenting bacteria (such as Sporomusa), who performed in situ gas fermentation leading to the synthesis of VFAs, and organics-utilising bacteria (such as Aquitalea), who utilised VFAs to drive chromate reduction. These findings, combined with batch assays, elucidate the pathways orchestrating synergistic interactions between fermentative microbial cohorts and chromate-reducing microorganisms. The findings facilitate the development of cost-effective strategies for groundwater and drinking water remediation and present an alternative application scenario for syngas.

Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity.

PURPOSE: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. METHODS: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). RESULTS: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). CONCLUSIONS: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

Nanobodies against African swine fever virus p72 and CD2v proteins as reagents for developing two cELISAs to detect viral antibodies.

African swine fever virus (ASFV) poses a significant threat to the global swine industry. Currently, there are no effective vaccines or treatments available to combat ASFV infection in pigs. The primary means of controlling the spread of the disease is through rapid detection and subsequent elimination of infected pig. Recently, a lower virulent ASFV isolate with a deleted EP402R gene (CD2v-deleted) has been reported in China, which further complicates the control of ASFV infection in pig farms. Furthermore, an EP402R-deleted ASFV variant has been developed as a potential live attenuated vaccine candidate strain. Therefore, it is crucial to develop detection methods that can distinguish wild-type and EP402R-deleted ASFV infections. In this study, two recombinant ASFV-p72 and -CD2v proteins were expressed using a prokaryotic system and used to immunize Bactrian camels. Subsequently, eight nanobodies against ASFV-p72 and ten nanobodies against ASFV-CD2v were screened. Following the production of these nanobodies with horse radish peroxidase (HRP) fusion proteins, the ASFV-p72-Nb2-HRP and ASFV-CD2v-Nb22-HRP fusions were selected for the development of two competitive ELISAs (cELISAs) to detect anti-ASFV antibodies. The two cELISAs exhibited high sensitivity, good specificity, repeatability, and stability. The coincidence rate between the two cELISAs and commercial ELISA kits was 98.6% and 97.6%, respectively. Collectively, the two cELISA for detecting antibodies against ASFV demonstrated ease of operation, a low cost, and a simple production process. The two cELISAs could determine whether pigs were infected with wild-type or CD2v-deleted ASFV, and could play an important role in monitoring ASFV infections in pig farms.

Effects of landfill void fraction and moisture content on the formation of aerobic areas in a semi-aerobic bioreactor.

The main disposal method for municipal solid waste (MSW), including the growing worldwide volumes of kitchen waste, involves transport to landfills. Because kitchen waste is mainly composed of organic matter and has a high moisture content, large amounts of leachate and landfill gas are generated when it is sent to landfills. Therefore, rapid waste stabilization is essential. In this study, four semi-aerobic bioreactors (named NS, SS, MS, and LS) were established with void fractions of 33.76%, 39.84%, 44.62%, and 41.31%, respectively. The results showed that the void fractions of landfill directly affected the gas flow path. When the landfill void fraction was small (e.g., NS), most airflow traveled directly through the pipeline and minimal airflow entered the waste layer. When the landfill void fraction was large (e.g., MS), air easily entered the waste layer and some air flowed into the gas vent with the landfill gas. As the reaction proceeded, the void fraction gradually decreased due to gravity-induced sedimentation. During the water addition experiment, the voids were occupied by water, leading to formation of an anaerobic area. Among the four bioreactors, only MS had negligible formation of an anaerobic zone in the center. Methane (CH4) generation was detected only at the connection between the gas vent and the leachate collection pipe. A larger void fraction led to formation of a smaller anaerobic zone. The ratio of air flowing in pipeline was lowest in MS. These results indicated that a large void fraction promotes the decomposition of organic matter.

Metabolome-microbiome insights into therapeutic impact of 8-O-acetylharpagide against breast cancer in a murine model.

Iridoid glycosides extract, which is the main active extract of Ajuga decumbens Thunb, has been proved to have anti-breast cancer activity in previous studies. However, it is still unknown whether 8-O-acetylharpagide, a main active compound in the extract, has anti-breast cancer activity. In this study, 4 T1 breast cancer mice model was first successfully established. Then the anti-breast cancer effect of 8-O-acetylharpagide was systematically investigated. Feces were collected for metabolomics and 16S rRNA analysis to assess the potential mechanism. The results showed that 8-O-acetylharpagide was effective in reducing 4 T1 mouse tumor volume and weight compared with the model group. Metabolome analysis revealed 12 potential metabolite biomarkers in feces, mainly involved in primary bile acid biosynthesis and arachidonic acid metabolism. The 16S rRNA sequencing results demonstrated that 8-O-acetylharpagide modulated the abundance of the intestinal flora in 4 T1 mice. Spearman correlation analysis showed that calcitriol and prostaglandin G2 strongly correlated with Akkermansia, Firmicutes and Muribaculum. Overall, the active compound 8-O-acetylharpagide could inhibit significantly breast cancer growth in 4 T1 breast cancer model mice. The mechanism of the anti-breast cancer effect of 8-O-acetylharpagide may be related to the regulation of primary bile acid biosynthesis and arachidonic acid metabolism and modulation of the abundance of Akkermansia and Firmicutes.

Spray-lithography of hybrid graphene-perovskite paper-based photodetectors for sustainable electronics.

Paper is an ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems. When combined with nanomaterial-based devices, it can be harnessed for various Internet-of-Things applications, ranging from wearable electronics to smart packaging. However, paper remains a challenging substrate for electronics due to its rough and porous nature. In addition, the absence of established fabrication methods is impeding its utilization in wearable applications. Unlike other paper-based electronics with added layers, in this study, we present a scalable spray-lithography on a commercial paper substrate. We present a non-vacuum spray-lithography of chemical vapor deposition (CVD) single-layer graphene (SLG), carbon nanotubes (CNTs), and perovskite quantum dots (QDs) on a paper substrate. This approach combines the advantages of two large-area techniques: CVD and spray-coating. The first technique allows for the growth of SLG, while the second enables the spray coating of a mask to pattern CVD SLG, electrodes (CNTs), and photoactive (QDs) layers. We harnessed the advantages of perovskite QDs in photodetection, leveraging their strong absorption coefficients. Integrating them with the graphene enhanced the photoconductive gain mechanism, leading to high external responsivity. The presented device shows high external responsivity of ~520A/W at 405nm at <1V bias due to photoconductive gain mechanism. The prepared paper-based photodetectors (PDs) achieved an external responsivity of 520 A/W under 405 nm illumination at <1V operating voltage. To the best of our knowledge, our devices have the highest external responsivity amongst paper-based PDs. By fabricating arrays of PDs on a paper substrate in the air, this work highlights the potential of this scalable approach for enabling ubiquitous electronics on paper.

Liver fibrosis showed a two-phase regression rate during long-term anti-HBV therapy by three-time biopsies assessments.

BACKGROUND: Evidence has proven that liver fibrosis or even cirrhosis can be reversed by anti-HBV treatment. However, the difference of fibrosis regression rates in short-term and long-term antiviral therapy remain unclear. Therefore, we aimed to identify the dynamic changes in fibrosis regression rate in patients with three-time liver biopsies during 5 years antiviral therapy. METHODS: CHB patients with three times of liver biopsies (baseline, after 1.5-year and 5-year antiviral therapy) from a prospective cohort were enrolled. All patients were biopsy-proved Ishak stage ≥ 3 at baseline (n = 92). Fibrosis regression was defined as Ishak stage decreased ≥ 1 or predominantly regressive categorized by P-I-R score. RESULTS: Totals of 65.2% (60/92) and 80.4% (74/92) patients attained fibrosis regression after 1.5-year and 5-year therapy, respectively. Median HBV DNA level declined from 6.5 log IU/ml (baseline) to 0 log IU/ml (1.5 years and 5 years, P < 0.001). The mean level of Ishak fibrosis stage in all patients decreased from stage 4.1 (baseline) to 3.7 (1.5 years) then 3.2 (5 years). Fibrosis regression rates were 0.27 stage/year between baseline to year 1.5 and 0.14 stage/year between year 1.5 and year 5. Furthermore, for patients who attained fibrosis regression after 5-year antiviral therapy, the two-phase regression rates were 0.39 stage/year (0 year-1.5 years) and 0.20 stage/year (1.5 years-5 years). This two-phase feature of regression rate was further confirmed by fully-quantification assessment of liver fibrosis based on SHG/TPEF. CONCLUSION: During the 5 years of long-term antiviral treatment, liver fibrosis rapidly regresses in the first 1.5 years before slowing down in the following 3.5 years.

Prevalence of sarcopenic obesity in the older non-hospitalized population: a systematic review and meta-analysis.

BACKGROUND: Sarcopenic obesity emerges as a risk factor for adverse clinical outcomes in non-hospitalized older adults, including physical disabilities, metabolic diseases, and even mortality. In this systematic review and meta-analysis, we investigated the overall SO prevalence in non-hospitalized adults aged ≥ 65 years and assessed the sociodemographic, clinicobiological, and lifestyle factors related to SO. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies reporting the prevalence of SO from database inception to October 2023. Two researchers independently screened the literature, evaluated the study quality, and extracted the data. Both fixed- and random-effects models were used in the meta-analysis to estimate the pooled SO prevalence and perform subgroup analyses. Publication and sensitivity bias analyses were performed to test the robustness of the associations. RESULTS: Among 46 studies eligible for review and a total of 71,757 non-hospitalized older adults, the combined prevalence of SO was 14% (95% CI:11-17%, I2 = 99.5%, P < 0.01). Subgroup analysis according to lifestyle factors demonstrated that the SO prevalence was 17% (95% CI: 8-29%, I2 = 99.5%, P < 0.01) in older adults without exercise habits. Regarding clinicobiological factors, older adults with a history of falls (15% [95% CI: 10-22%, I2 = 82%, P < 0.01]), two or more chronic diseases (19% [95% CI: 10-29%, I2 = 97%, P < 0.01]), functional impairment (33% [95% CI: 29-37%, I2 = 0%, P = 0.95]), cognitive impairment (35% [95% CI: 9-65%, I2 = 83%, P = 0.02]), osteoporosis (20% [95% CI: 8-35%, I2 = 96%, P < 0.01]), high fasting glucose level (17% [95% CI: 1-49%, I2 = 98%, P < 0.01]), or the use of antipsychotics (13% [95% CI: 2-28%, I2 = 0%, P = 0.32]) exhibited a higher SO prevalence. CONCLUSION: SO prevalence is high among non-hospitalized older adults, especially those with functional and cognitive impairments. Thus, SO is a potential problem for the aging population; implementation of planned interventions in the community is needed to reduce the prevalence and adverse outcomes of SO.

Rapid Photoacoustic Exhaust Gas Analyzer for Simultaneous Measurement of Nitrogen Dioxide and Sulfur Dioxide.

A rapid photoacoustic (PA) exhaust gas analyzer is presented for simultaneous measurements of nitrogen dioxide (NO2) and sulfur dioxide (SO2). A laser diode (LD) emitting at 450 nm and a light-emitting diode (LED) with a peak wavelength of 275 nm operated simultaneously, producing PA signals of NO2 and SO2, respectively. The LD and LED were modulated at different frequencies of 2568 and 2570 Hz, and their emission light beams were transmitted through two resonant tubes in a differential PA cell (DPAC), respectively. A self-made dual-channel digital lock-in amplifier was used to realize the simultaneous detection of dual-frequency PA signals. Cross interference between the PA signals at the two different frequencies was reduced to 0.02% by using a lock-in amplifier. In order to achieve a rapid dynamic measurement, gas sampling was accelerated by an air pump. The use of mufflers and the differential PA detection technique significantly reduced the gas sampling noise. When the gas flow rate was 1000 sccm, the response time of the PA dual-gas analyzer was 8 and 17 s for NO2 and SO2, respectively. The minimum detection limits of NO2 and SO2 were 1.7 and 26.1 ppb when the averaging time of the system was 10 s, respectively. Due to the wide spectral bandwidth of the LED, NO2 produced an interference to the detection of SO2. The interference was reduced by the precise detection of NO2. Since the radiations of the LD and LED passed through two different PA tubes, the impact of NO2 photochemical dissociation caused by UV LED luminescence on NO2 gas detection was negligible. The sharing of the PA cell, the gas lines, and the signal processing modules significantly reduced the size and cost of the PA dual-gas analyzer.