Insight to the Catalytic Activity of Atomically Precise Ag4Ni2 Nanoclusters on Silicon Carbide for Nitroarene Reduction.

Atomically precise Ag4Ni2 nanoclusters with 2,4-dimethylbenzenethiol as the ligands were synthesized and characterized as a cocatalyst of SiC for the selective hydrogenation of nitroarenes to arylamine in the presence of NaBH4. The obtained Ag4Ni2/SiC samples exhibited extraordinary catalytic activity, and a self-accelerated catalytic process was observed with the reduction of nitrophenol to aminophenol as the model reaction. Experimental comparison between the Ag4Ni2/SiC samples before and after the catalysis showed that the transformation of Ag4Ni2 clusters to polydisperse Ag particles as well as amorphous NiOx on the surface of SiC in the catalysis was the key to their high activity. AIMD calculations revealed that the transformation of Ag4Ni2 was driven by the presence of multiple hydrides on the cluster, which induced the detachment of the thiol ligand of the nanoclusters.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties.

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

Catalytic Hydrogenation of Nitroarenes over Ag33 Nanoclusters: The Ligand Effect.

Using ligand-protected metallic nanoclusters with atomic precision as catalysts and elucidating its ligand effect in the catalysis are the prerequisites to deepen the structure-catalysis relationship of nanoclusters at the molecular level. Herein, a series of Ag33 nanoclusters protected with different thiolate ligands (2-phenylethanethiol, 4-chlorobenzyl mercaptan, and 4-methoxybenzyl mercaptan as precursors) were synthesized and used as heterogeneous catalysts for the conversion of nitroarenes to arylamine with NaBH4 as reductant. The obtained nanoclusters exhibited ligand-dependent catalytic activity, with benzyl thiolate ligands distinctly superior to the phenethyl thiolate ligands. DFT calculations revealed that the ligand regulated catalytic activity of the nanoclusters was ascribed to the H-π and π-π interactions between the ligands and the substrates, owing to the presence of phenyl rings in these structures. This work highlighted the importance of the ligands on the metallic nanoclusters in catalysis and provides a strategy to regulate the catalytic activity by utilizing weak interactions between the catalysts and the substrates.

Causal effects of maternal exposure to PM2.5 during pregnancy on depression symptoms in adolescence: Identifying vulnerable windows and subpopulations in a national cohort study.

Few studies have examined the causal relationship between chronic exposure to air pollutants during pregnancy and depression in adolescent offspring. In addition, it has not been investigated whether exposure is most harmful to adolescents in certain populations and at certain stages of pregnancy. A total of 1975 adolescents from 1632 families from the China Family Panel Study, a representative national longitudinal cohort, were included in this study. We used high-resolution satellite retrieval data to assess the PM2.5 exposure of mothers during pregnancy. Specifically, we employed a two-stage instrumental variable model (IV-2SLS) within the counterfactual causal inference framework, and selected and validated appropriate instruments, thereby mitigating potentially biased results arising from bi-direction between dependent and independent variables. This approach allowed us to explore the causal relationship between maternal PM2.5 exposure during pregnancy and adolescent depression symptoms. The endogeneity of air pollution during pregnancy and the need for a causal model were suggested by the results of the model comparisons. Using the IV-2SLS model, we found that maternal exposure to PM2.5 during pregnancy exacerbates depressive symptoms in the offspring during adolescence (ß = 0.2, 95% CI: 0.05-0.34). We also found that exposure during the first trimester may cause greater harm. Adolescents with low household income, being male, irregular exercise habits, living in rural areas, and having mothers with poorer mental status may be more vulnerable. The findings suggest that maternal exposure to PM2.5 during pregnancy may have a negative impact on the depression symptoms of offspring in adolescence and that more attention should be paid to vulnerable populations and the window of vulnerability.

Silicone gel sheeting for treating keloid scars.

BACKGROUND: Keloid scarring is one of the most common types of pathological scarring. Keloid scars that fail to heal can affect a person's physical and psychological function by causing pain, pruritus, contractures, and cosmetic disfigurement. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for keloid scars. However, there is no up-to-date systematic review assessing the effectiveness of SGS for keloid scars. A clear and rigorous review of current evidence is required to guide clinicians, healthcare managers and people with keloid scarring. OBJECTIVES: To assess the effectiveness of silicone gel sheeting for the treatment of keloid scars compared with standard care or other therapies. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was December 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited people with any keloid scars and assessed the effectiveness of SGS. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment, data extraction and GRADE assessment of the certainty of evidence. We resolved initial disagreements by discussion, or by consulting a third review author when necessary. MAIN RESULTS: Two studies met the inclusion criteria. Study sample sizes were 16 and 20 participants. The trials were clinically heterogeneous with differences in causes for scarring (e.g. surgery, infected wounds, and trauma), site (e.g. chest and back), and ages of scars. The duration of follow-up was three and four and a half months. The included studies reported three comparisons; SGS compared with no treatment, SGS compared with non-silicone gel sheeting (a dressing similar to SGS but which does not contain silicone), and SGS compared with intralesional injections of triamcinolone acetonide. One trial had a split-body design and one trial had an unclear design (resulting in a mix of paired and clustered data). The included studies reported limited outcome data for the primary review outcome of scar severity measured by health professionals and no data were reported for severity of scar measured by patients or adverse events. For secondary outcomes some data on pain were reported, but health-related quality of life and cost-effectiveness were not reported. Both trials had suboptimal outcome reporting, thus many domains in the risk of bias were assessed as unclear. All evidence was rated as being very low-certainty, mainly due to risk of bias, indirectness, and imprecision.  SGS compared with no treatment Two studies with 33 participants (76 scars) reported the severity of scar assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with no treatment (very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). We are uncertain about the effect of SGS on pain compared with no treatment (21 participants with 40 scars; very low-certainty evidence, downgraded once for risk of bias, once for inconsistency, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with non-SGS One study with 16 participants (25 scars) was included in this comparison. We are uncertain about the effect of SGS on scar severity assessed by health professionals compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). We are also uncertain about the effect of SGS on pain compared with non-SGS (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. SGS compared with intralesional injections of triamcinolone acetonide One study with 17 participants (51 scars) reported scar severity assessed by health professionals, and we are uncertain about the effect of SGS on scar severity compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and once for imprecision). This study also reported pain assessed by health professionals among 5 participants (15 scars) and we are uncertain about the effect of SGS on pain compared with intralesional injections of triamcinolone acetonide (very low-certainty evidence, downgraded once for risk of bias, once for indirectness, and twice for imprecision). No data were reported for other outcomes including scar severity assessed by patients, adverse events, adherence to treatment, health-related quality of life and cost-effectiveness. AUTHORS' CONCLUSIONS: There is currently a lack of RCT evidence about the clinical effectiveness of SGS in the treatment of keloid scars. From the two studies identified, there is insufficient evidence to demonstrate whether the use of SGS compared with no treatment, non-SGS, or intralesional injections of triamcinolone acetonide makes any difference in the treatment of keloid scars. Evidence from the included studies is of very low certainty, mainly driven by the risk of bias, indirectness, and imprecision due to small sample size. Further well-designed studies that have good reporting methodologies and address important clinical, quality of life and economic outcomes are required to reduce uncertainty around decision-making in the use of SGS to treat keloid scars.

I-125 seeds brachytherapy with transcatheter arterial chemoembolization for subcapsular hepatocellular carcinoma.

BACKGROUND: I-125 seeds brachytherapy (ISB) has been used to improve the clinical effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We aim to appraise the safety and clinical efficacy of combined ISB and TACE for the treatment of subcapsular HCC. MATERIALS AND METHODS: A retrospective investigative study extending from January 2017 to December 2020, involved individuals suffering from subcapsular HCC, who were subjected to TACE treatment with or without ISB in our center. The clinical effectiveness was compared between 2 groups. RESULTS: Sixty-four patients, in total, with subcapsular HCC had to undergo TACE with (n = 32) or without (n = 32) ISB in our center. After CT-guided ISB, only 2 (6.3%) patients experienced a self-limited pneumothorax. Combined treatment resulted in a significantly higher complete response (56.3% vs. 18.8%, P = 0.002) and total response (90.7% vs. 59.4%, P = 0.004) rates than that of TACE alone. In comparison to the TACE alone group, the median progression-free survival was substantially longer in the combined treatment group (11 months vs. 5 months, P = 0.016). Further, 15 and 28 patients in combined and TACE alone groups respectively died within the follow-up. The median OS was comparable between combined and TACE alone groups (22 months vs. 18 months, P = 0.529). CONCLUSIONS: Combined TACE and ISB therapy is a safe treatment method for individuals suffering from subcapsular HCC. When compared, combined treatment had significantly enhanced clinical efficacy as a subcapsular HCC therapy, in comparison to TACE alone.

Stress-related disorders and subsequent cancer risk and mortality: a population-based and sibling-controlled cohort study in Sweden.

Prior research has suggested a potential role of psychological stress on cancer development while the role of familial factors on this association is underexplored. We conducted a nationwide cohort study including 167,836 individuals with a first-onset stress-related disorder (including post-traumatic stress disorder, acute stress reaction, adjustment disorder and other stress reactions) diagnosed between 1981 and 2016 in Sweden (i.e., exposed patients), 1,631,801 birth year- and sex-matched unexposed individuals, and 179,209 unaffected full siblings of the exposed patients. Cox models were used to estimate the hazard ratios (HRs) of newly diagnosed cancer and cancer-related death, beyond 1 year after diagnosis of stress-related disorders. We further examined the potential mediation roles of behavior-related morbidities in the associations of stress-related disorders with smoking or alcohol-related cancer incidence and mortality. We found modestly elevated risks of cancer incidence and mortality among exposed patients compared with matched unexposed individuals (incidence: HR = 1.03, 95% CI 1.01-1.06; mortality: HR = 1.13, 95% CI 1.07-1.18), while not when comparing with full siblings (incidence: HR = 1.03, 95% CI 0.99-1.08; mortality: HR = 1.09, 95% CI 1.00-1.19). Similarly, the suggested elevations in incidence and mortality of individual cancer sites (or groups) in the population-based comparison attenuated towards null in the between-sibling comparison. The risk elevations for smoking or alcohol-related cancers in the population-based comparison (incidence: HR = 1.18, 95% CI 1.11-1.24; mortality: HR = 1.20, 95% CI 1.12-1.29) were partially mediated by alcohol-related morbidities during follow-up. Collectively, our findings suggest that the association between stress-related disorders and cancer risk and mortality is largely explained by familial factors, including shared behavioral hazards.

Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review.

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.

Depression in multiple sclerosis across the adult lifespan.

OBJECTIVES: The objective of this study is to examine the burden of depressive symptoms across the adult age span in people with multiple sclerosis (MS) and test if the relationship between depressive symptoms and MS characteristics vary across age groups. METHODS: In analyses of the MS Partners Advancing Technology and Health Solutions (MS PATHS) network of adults with MS, we compared the prevalence of depression in MS PATHS with non-MS controls across age and evaluated for effect modification by age in the association between depressive symptoms and clinical and neuroperformance measures via multivariable-adjusted regression models. RESULTS: In total, 13,821 individuals with MS were included. The prevalence of depression was higher in MS versus non-MS controls, but was similar between men/women across age. The association between depression and processing speed (PST; p for interaction = 0.009) or walking speed (p for interaction = 0.04) varied by age. For example, younger depressed individuals had 0.45 standard deviation (SD) (95% confidence interval (CI) = -0.62, -0.29) worse PST Z-scores versus non-depressed younger participants, whereas older depressed individuals had 0.20 SD (95% CI = -0.32, -0.08) worse PST Z-scores versus non-depressed older participants. CONCLUSION: Depressive symptoms and age should be considered when interpreting measures of walking speed and cognitive function; these findings may have implications for analyses of neuroperformance change.

Hospital bed supply and inequality as determinants of maternal mortality in China between 2004 and 2016.

BACKGROUND: Driven by the government's firm commitment to promoting maternal health, maternal mortality ratio (MMR) in China has achieved a remarkable reduction over the past 25 years. Paralleled with the decline of MMR has been the expansion of hospital bed supply as well as substantial reduction in hospital bed distribution inequalities, which were thought to be significant contributors to the reduction in MMR. However, evidences on the impact of hospital bed supply as well as how its distribution inequality has affected MMR remains scarce in China. Addressing this uncertainty is essential to understand whether efforts made on the expansion of healthcare resource supply as well as on improving its distribution inequality from a geographical perspective has the potential to produce measurable population health improvements. METHODS: Panel data of 31 provinces in China between 2004 and 2016 were extracted from the national statistical data, including China Statistical Yearbooks, China Health Statistical Yearbooks and other national publications. We firstly described the changes in hospital bed density as well as its distribution inequality from a geographical perspective. Then, a linear mixed model was employed to evaluate the impact of hospital bed supply as well as its distribution inequality on MMR at the provincial level. RESULTS: The MMR decreased substantially from 48.3 to 19.9 deaths per 100,000 live births between 2004 and 2016. The average hospital bed density increased from 2.28 per 1000 population in 2004 to 4.54 per 1000 population in 2016, with the average Gini coefficient reducing from 0.32 to 0.25. As indicated by the adjusted mixed-effects regressions, hospital bed density had a negative association with MMR (ß = - 0.112, 95% CI: - 0.210--0.013) while every 0.1-unit reduction of Gini coefficient suggested 14.50% decline in MMR on average (ß = 1.354, 95% CI: 0.123-2.584). Based on the mediation analysis, the association between hospital bed density or Gini coefficient with MMR was found to be significantly mediated by facility birth rate, especially during the period from 2004 to 2009. CONCLUSIONS: This study provided empirical evidences on China's impressive success in the aspect of reducing MMR which could be attributed to the expansion of hospital beds as well as the improvement in its distribution inequality from a geographical perspective. Such findings were expected to provide evidence-based implications for long-term policy-making procedures in order to achieve rational healthcare resource allocations as well as promoting the equity and accessibility to obtaining health care from a holistic perspective. Constant efforts should be made on improving the equity in healthcare resource allocations in order to achieve the penetration of universal healthcare coverage.

Silicone gel sheeting for treating hypertrophic scars.

BACKGROUND: Each year, in high-income countries alone, approximately 100 million people develop scars. Excessive scarring can cause pruritus, pain, contractures, and cosmetic disfigurement, and can dramatically affect people's quality of life, both physically and psychologically. Hypertrophic scars are visible and elevated scars that do not spread into surrounding tissues and that often regress spontaneously. Silicone gel sheeting (SGS) is made from medical-grade silicone reinforced with a silicone membrane backing and is one of the most commonly used treatments for hypertrophic scars. OBJECTIVES: To assess the effects of silicone gel sheeting for the treatment of hypertrophic scars in any care setting. SEARCH METHODS: In April 2021 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled people with any hypertrophic scars and assessed the use of SGS. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, 'Risk of bias' assessment, data extraction and GRADE assessment of the certainty of evidence. We resolved initial disagreements by discussion, or by consulting a third review author when necessary. MAIN RESULTS: Thirteen studies met the inclusion criteria. Study sample sizes ranged from 10 to 60 participants. The trials were clinically heterogeneous with differences in duration of follow-up, and scar site. We report 10 comparisons, SGS compared with no SGS treatment and SGS compared with the following treatments: pressure garments; silicone gel; topical onion extract; polyurethane; propylene glycol and hydroxyethyl cellulose sheeting; Kenalog injection; flashlamp-pumped pulsed-dye laser; intense pulsed light  and Gecko Nanoplast (a silicone gel bandage). Six trials had a split-site design and three trials had an unclear design (resulting in a mix of paired and clustered data). Included studies reported limited outcome data for the primary review outcomes of severity of scarring measured by health professionals and adverse events (limited data reported by some included studies, but further analyses of these data was not possible) and no data were reported for severity of scarring reported by patients. For secondary outcomes some pain data were reported, but health-related quality of life and cost effectiveness were not reported. Many trials had poorly-reported methodology, meaning the risk of bias was unclear. We rated all evidence as being either of low or very low certainty, often because of imprecision resulting from few participants, low event rates, or both, all in single studies. SGS compared with no SGS Seven studies with 177 participants compared SGS with no SGS for hypertrophic scars. Two studies with 31 participants (32 scars) reported severity of scarring assessed by health professionals, and it is uncertain whether there is a difference in severity of scarring between the two groups (mean difference (MD) -1.83, 95% confidence interval (CI) -3.77 to 0.12; very low-certainty evidence, downgraded once for risk of bias, and twice for serious imprecision). One study with 34 participants suggests SGS may result in a slight reduction in pain level compared with no SGS treatment (MD -1.26, 95% CI -2.26 to -0.26; low-certainty evidence, downgraded once for risk of bias and once for imprecision). SGS compared with pressure garments One study with 54 participants was included in this comparison. The study reported that SGS may reduce pain levels compared with pressure garments (MD -1.90, 95% CI -2.99 to -0.81;  low-certainty evidence, downgraded once for risk of bias and once for imprecision). SGS compared with silicone gel One study with 32 participants was included in this comparison. It is unclear if SGS impacts on severity of scarring assessed by health professionals compared with silicone gel (MD 0.40, 95% CI -0.88 to 1.68; very low-certainty evidence, downgraded once for risk of bias, twice for imprecision). SGS compared with topical onion extract One trial (32 participants) was included in this comparison. SGS may slightly reduce severity of scarring compared with topical onion extract (MD -1.30, 95% CI -2.58 to -0.02; low-certainty evidence, downgraded once for risk of bias, and once for imprecision). SGS compared with polyurethane One study with 60 participants was included in this comparison. It is unclear if SGS impacts on the severity of scarring assessed by health professionals compared with polyurethane (MD 0.50, 95% CI -2.96 to 3.96; very low-certainty evidence, downgraded once for risk of bias, and twice for imprecision). SGS compared with self-adhesive propylene glycol and hydroxyethyl cellulose sheeting One study with 38 participants was included in this comparison. It is uncertain if SGS reduces pain compared with self-adhesive propylene glycol and hydroxyethyl cellulose sheeting (MD -0.12, 95% CI -0.18 to -0.06). This is very low-certainty evidence, downgraded once for risk of bias, once for imprecision and once for indirectness. SGS compared with Gecko Nanoplast One study with 60 participants was included in this comparison. It is unclear if SGS impacts on pain compared with Gecko Nanoplast (MD 0.70, 95% CI  -0.28 to 1.68; very low-certainty evidence, downgraded once for risk of bias and twice for imprecision. There was a lack of reportable data from the other three comparisons of SGS with Kenalog injection, flashlamp-pumped pulsed-dye laser or intense pulsed light. AUTHORS' CONCLUSIONS: There is currently limited rigorous RCT evidence available about the clinical effectiveness of SGS in the treatment of hypertrophic scars. None of the included studies provided evidence on severity of scarring validated by participants, health-related quality of life, or cost effectiveness. Reporting was poor, to the extent that we are not confident that most trials are free from risk of bias. The limitations in current RCT evidence suggest that further trials are required to reduce uncertainty around decision-making in the use of SGS to treat hypertrophic scars.

Estimating Phase Amplitude Coupling between Neural Oscillations Based on Permutation and Entropy.

Cross-frequency phase-amplitude coupling (PAC) plays an important role in neuronal oscillations network, reflecting the interaction between the phase of low-frequency oscillation (LFO) and amplitude of the high-frequency oscillations (HFO). Thus, we applied four methods based on permutation analysis to measure PAC, including multiscale permutation mutual information (MPMI), permutation conditional mutual information (PCMI), symbolic joint entropy (SJE), and weighted-permutation mutual information (WPMI). To verify the ability of these four algorithms, a performance test including the effects of coupling strength, signal-to-noise ratios (SNRs), and data length was evaluated by using simulation data. It was shown that the performance of SJE was similar to that of other approaches when measuring PAC strength, but the computational efficiency of SJE was the highest among all these four methods. Moreover, SJE can also accurately identify the PAC frequency range under the interference of spike noise. All in all, the results demonstrate that SJE is better for evaluating PAC between neural oscillations.

Pd-Mediated Synthesis of Ag33 Chiral Nanocluster with Core-Shell Structure in T Point Group.

We report a Pd-mediated synthesis and crystal structure of a new chiral Ag33(SCH2CH2Ph)24(PPh3)4 nanocluster with an open shell electronic structure. The single-crystal X-ray structure reveals that the kernel of the cluster comprises a keplerate Ag13 icosahedron core with one Ag atom in the center and a shell framework of Ag20S24P4 block. The Ag20S24P4 shell framework is fully arranged by helical -S-Ag-S- staples along four Ag-P bonds involved C3 axis, which endows the kernel structure of the nanocluster chirality and symmetry in the T point group. The geometry and chirality of the Ag33 nanocluster are further confirmed by nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) spectra, and time-dependent density functional theory calculations. Our results show that the formation of the new chiral Ag33 nanocluster is strongly dependent on the presence of Pd regent with the form of Pd(PPh3)4 functioning in the synthesis. This work not only presents a novel chiral structure of the silver nanocluster but also provides a new strategy for the development of a novel nanocluster.

Comparative transcriptomics and proteomics analysis of the symbiotic germination of Paphiopedilum barbigerum with Epulorhiza sp. FQXY019.

Introduction: Paphiopedilum barbigerum is currently the rarest and most endangered species of orchids in China and has significant ornamental value. The mature seeds of P. barbigerum are difficult to germinate owing to the absence of an endosperm and are highly dependent on mycorrhizal fungi for germination and subsequent development. However, little is known about the regulation mechanisms of symbiosis and symbiotic germination of P. barbigerum seeds. Methods: Herein, transcriptomics and proteomics were used to explore the changes in the P. barbigerum seeds after inoculation with (FQXY019 treatment group) or without (control group) Epulorhiza sp. FQXY019 at 90 days after germination. Results: Transcriptome sequencing revealed that a total of 10,961 differentially expressed genes (DEGs; 2,599 upregulated and 8,402 downregulated) were identified in the control and FQXY019 treatment groups. These DEGs were mainly involved in carbohydrate, fatty acid, and amino acid metabolism. Furthermore, the expression levels of candidate DEGs related to nodulin, Ca2+ signaling, and plant lectins were significantly affected in P. barbigerum in the FQXY019 treatment groups. Subsequently, tandem mass tag-based quantitative proteomics was performed to recognize the differentially expressed proteins (DEPs), and a total of 537 DEPs (220 upregulated and 317 downregulated) were identified that were enriched in processes including photosynthesis, photosynthesis-antenna proteins, and fatty acid biosynthesis and metabolism. Discussion: This study provides novel insight on the mechanisms underlying the in vitro seed germination and protocorm development of P. barbigerum by using a compatible fungal symbiont and will benefit the reintroduction and mycorrhizal symbiotic germination of endangered orchids.

Symbiotic seed germination and seedling growth of mycorrhizal fungi in Paphiopedilum hirsutissimun (Lindl.Ex Hook.) Stein from China.

Similar to other orchid species, Paphiopedilum hirsutissimum (Lindl.ex Hook.) Stein, relies on nutrients provided by mycorrhizal fungus for seed germination and seedling development in the wild owing to a lack of endosperm in its seeds. Therefore, obtaining suitable and specialized fungi to enhance seed germination, seedling formation, and further development is considered a powerful tool for orchid seedling propagation, reintroduction, and species conservation. In this study, we investigated the diversity, abundance, and frequency of endophytic fungal strains in the root organs of P. hirsutissimum. One family and five genera of the fungi were isolated and identified through rDNA-ITS sequencing. The ability of isolated fungi to germinate in vitro from the seeds of this species was evaluated, and the development of P. hirsutissimum protocorm has been described. The findings showed that the treatments inoculated with endophytic fungal DYXY033 may successfully support the advanced developmental stage of seedlings up to stage 5. In addition, scanning electron microscopy (SEM) revealed that the mycelium of this strain began to invade from either end of the seeds up to the embryo, extending rapidly from the inside to the outside. Its lengthening resulted in the bursting of the seed coat to form protocorms, which developed into seedlings. The results showed that DYXY033 has a high degree of mycobiont specificity under in vitro symbiotic seed germination conditions and is a representative mycorrhizal fungus with ecological value for the species. In summary, this strain may particularly be significant for the protection of P. hirsutissimum species that are endangered in China. In the long run, it may also contribute to global efforts in reintroducing orchid species and in realizing in situ restorations of threatened orchid populations.

Values of new ultrasonic imaging methods for the diagnosis of apical Takotsubo syndrome.

Background: Takotsubo syndrome (TTS) is a multifactorial disease contributed to by several pathological factors. It is characterized by transient left ventricular dysfunction, and patients with TTS can spontaneously recover within days or weeks. This study's objective was to investigate the ultrasonic characteristics of TTS during different periods and assess the clinical application value of real-time 3-dimensional echocardiography (RT-3DE) and speckle tracking imaging (STI) in TTS. Methods: In this prospective cohort study, the patients with apical TTS were evaluated by echocardiography on admission (within 1-3 days) and after 4 and 8 weeks. RT-3DE was performed to observe the structure and function of the left ventricle (LV). LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF) were calculated. The longitudinal peak systolic strain (LPSS) of all LV myocardial segments was acquired by 2D STI. For comparison, 20 healthy individuals were included as normal controls. Results: A total of 16 patients with TTS were included. Their LV was characterized as an "octopus pot" in morphology with obvious hypokinesis on admission. The LVEDV, LVESV, LVSV, and LVEF were 84.23±10.67, 55.94±8.51, 28.31±8.06 mL, and 33.59%±4.12%, respectively, in patients with TTS on admission with a significant difference from those of the controls (P=0.005, P<0.001, P<0.001, and P<0.001, respectively). A definite improvement was found upon follow-up, with these parameters even returning to normal morphology after 8 weeks. The LVEDV, LVESV, LVSV, and LVEF were 75.79±6.86, 28.05±4.33, 47.81±3.57 mL, and 63.02%±3.92%, respectively, in TTS patients after 8 weeks with no significant difference from those of the controls (P=0.907, P=0.235, P=0.162, and P=0.052, respectively). A significant decrease in LPSS was also found in patients with TTS on admission. In the eighth week of follow-up, the LPSS of the apical and middle segments in TTS patients remained significantly decreased compared with that of the normal controls (-18.54%±4.69% vs. -24.29%±3.46%, P<0.001; -19.38%±2.88% vs. -22.36%±3.23%, P<0.001), but that of the basal segments in TTS patients returned to normal and there was no significant differences from the normal controls (-20.75%±2.91% vs. -21.51%±2.85%; P=0.055). Conclusions: RT-3DE and STI played an indispensable role in visually and quantitatively inspecting the abnormalities of patients with TTS, including in diagnosis and follow-up.

A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.

Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.

Physiological functions of podosomes: From structure and function to therapy implications in osteoclast biology of bone resorption.

With increasing age, bone tissue undergoes significant alterations in composition, architecture, and metabolic functions, probably causing senile osteoporosis. Osteoporosis possess the vast majority of bone disease and associates with a reduction in bone mass and increased fracture risk. Bone loss is on account of the disorder in osteoblast-induced bone formation and osteoclast-induced bone resorption. As a unique bone resorptive cell type, mature bone-resorbing osteoclasts exhibit dynamic actin-based cytoskeletal structures called podosomes that participate in cell-matrix adhesions specialized in the degradation of mineralized bone matrix. Podosomes share many of the same molecular constitutions as focal adhesions, but they have a unique structural organization, with a central core abundant in F-actin and encircled by scaffolding proteins, kinases and integrins. Here, we conclude recent advancements in our knowledge of the architecture and the functions of podosomes. We also discuss the regulatory pathways in osteoclast podosomes, providing a reference for future research on the podosomes of osteoclasts and considering podosomes as a therapeutic target for inhibiting bone resorption.