Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins.

The architectural protein histone-like protein from Escherichia coli strain U93 (HU) is the most abundant bacterial DNA binding protein and highly conserved among bacteria and Apicomplexan parasites. It not only binds to double-stranded DNA (dsDNA) to maintain DNA stability but also, interacts with RNAs to regulate transcription and translation. Importantly, HU is essential to cell viability for many bacteria; hence, it is an important antibiotic target. Here, we report that Gp46 from bacteriophage SPO1 of Bacillus subtilis is an HU inhibitor whose expression prevents nucleoid segregation and causes filamentous morphology and growth defects in bacteria. We determined the solution structure of Gp46 and revealed a striking negatively charged surface. An NMR-derived structural model for the Gp46-HU complex shows that Gp46 occupies the DNA binding motif of the HU and therefore, occludes DNA binding, revealing a distinct strategy for HU inhibition. We identified the key residues responsible for the interaction that are conserved among HUs of bacteria and Apicomplexans, including clinically significant Mycobacterium tuberculosis, Acinetobacter baumannii, and Plasmodium falciparum, and confirm that Gp46 can also interact with these HUs. Our findings provide detailed insight into a mode of HU inhibition that provides a useful foundation for the development of antibacteria and antimalaria drugs.

Metal complexes bearing EGFR-inhibiting ligands as promising anticancer agents.

Overexpression of the epidermal growth factor receptor (EGFR, erbB1) has been observed in a wide range of solid tumors and has frequently been associated with poor prognosis. As a result, EGFR inhibition has become an attractive anticancer drug design strategy, and a large number of small molecular inhibitors have been developed. Despite the widespread clinical use of EGFR tyrosine kinase inhibitors (TKIs), their drug resistance, inadequate accumulation in tumors, and severe side effects have spurred the search for better antitumor drugs. Metal complexes have attracted much attention because of their different mechanisms compared with EGFR-TKIs. Therefore, the combination of metals and inhibitors is a promising anticancer strategy. For example, Ru and Pt centers are introduced to design complexes with double or multiple targets, while Au complexes are combined with inhibitors to overcome drug resistance. Co complexes are designed as prodrugs with weak side effects and enhanced targeting by the hypoxia activation strategy, and other metals such as Rh and Fe enhance the anticancer effect of the complexes. In addition, the introduction of Ga center is beneficial to the development of nuclear imaging tracers. In this paper, metal EGFR-TKI complexes in the last 15 years are reviewed, their mechanisms are briefly introduced, and their advantages are summarized.

PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.

Homochiral Nanopropeller via Chiral Active Surface Growth.

Under the control of chiral ligand glutathione and in the presence of hexadecyltrimethylammonium bromide, Au deposition on Au seeds is known to give chiral nanostructures. We have previously shown that the protruding chiral patterns, as opposed to flat facets, are likely caused by active surface growth, where nonuniform ligand coverage could be responsible for the focused growth at a few active sites. By pushing the limit of such a growth mode, here, we use decahedral seeds to prepare homochiral nanopropellers with intricate patterns of deep valleys and protruding ridges. Control experiments show that the focused growth depends on the rates of Au deposition by changing either the seed concentration or the reductant concentration, consistent with the proposed mechanism. The dynamic growth competition between the ligand-deficient active sites and the ligand-rich surfaces gradually focuses the growth onto a few active sites, causing the expansion of grooves, squeezing of steep ridges, and a surprising 36° rotation of the pentagonal outline. The imbalanced deposition on the prochiral slopes is responsible for the tilted grooves, the twisted walls, and thus the well-separated and distorted blades, which become the origin of the chiroptical responses.

The role of proliferating stem-like plasma cells in relapsed or refractory multiple myeloma: Insights from single-cell RNA sequencing and proteomic analysis.

The management and comprehension of relapsed or refractory multiple myeloma (RRMM) continues to pose a significant challenge. By integrating single-cell RNA sequencing (scRNA-seq) data of 15 patients with plasma cell disorders (PCDs) and proteomic data obtained from mass spectrometry-based analysis of CD138+ plasma cells (PCs) from 144 PCDs patients, we identified a state of malignant PCs characterized by high stemness score and increased proliferation originating from RRMM. This state has been designated as proliferating stem-like plasma cells (PSPCs). NUCKS1 was identified as the gene marker representing the stemness of PSPCs. Comparison of differentially expressed genes among various PC states revealed a significant elevation in LGALS1 expression in PSPCs. Survival analysis on the MMRF CoMMpass dataset and GSE24080 dataset established LGALS1 as a gene associated with unfavourable prognostic implications for multiple myeloma. Ultimately, we discovered three specific ligand-receptor pairs within the midkine (MDK) signalling pathway network that play distinct roles in facilitating efficient cellular communication between PSPCs and the surrounding microenvironment cells. These insights have the potential to contribute to the understanding of molecular mechanism and the development of therapeutic strategies involving the application of stem-like cells in RRMM treatment.

Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients.

BACKGROUND: Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. METHODS: Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. RESULTS: There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. CONCLUSION: The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

SRS 16-86 promotes diabetic nephropathy recovery by regulating ferroptosis.

Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM), and cell death plays an important role. Ferroptosis is a recently discovered type of iron-dependent cell death and one that is different from other kinds of cell death including apoptosis and necrosis. However, ferroptosis has not been described in the context of DN. This study explored the role of ferroptosis in DN pathophysiology and aimed to confirm the efficacy of the ferroptosis inhibitor SRS 16-86 on DN. Streptozotocin injection was used to establish the DM and DN animal models. To investigate the presence or occurrence of ferroptosis in DN, we assessed the concentrations of iron, reactive oxygen species and specific markers associated with ferroptosis in a rat model of DN. Additionally, we performed haematoxylin-eosin staining, blood biochemistry, urine biochemistry and kidney function analysis to evaluate the efficacy of the ferroptosis inhibitor SRS 16-86 in ameliorating DN. We found that SRS 16-86 could improve the recovery of renal function after DN by upregulating glutathione peroxidase 4, glutathione and system xc -light chain and by downregulating the lipid peroxidation markers and 4-hydroxynonenal. SRS 16-86 treatment could improve renal organization after DN. The inflammatory cytokines interleukin 1ß and tumour necrosis factor α and intercellular adhesion molecule 1 were significantly decreased following SRS 16-86 treatment after DN. The results indicate that there is a strong connection between ferroptosis and the pathological mechanism of DN. The efficacy of the ferroptosis inhibitor SRS 16-86 in DN repair supports its use as a new therapeutic treatment for DN.

Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant.

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen.

Lipid metabolism mediates the association between body mass index change and bone mineral density: The Taizhou imaging study.

BACKGROUND: Limited research explores the impact of body mass index (BMI) change on osteoporosis, regarding the role of lipid metabolism. We aimed to cross-sectionally investigate these relationships in 820 Chinese participants aged 55-65 from the Taizhou Imaging Study. METHODS: We used the baseline data collected between 2013 and 2018. T-score was calculated by standardizing bone mineral density and was used for osteoporosis and osteopenia diagnosis. Multinomial logistic regression was used to examine the effect of BMI change on bone health status. Multivariable linear regression was employed to identify the metabolites corrected with BMI change and T-score. Exploratory factor analysis (EFA) and mediation analysis were conducted to ascertain the involvement of the metabolites. RESULTS: BMI increase served as a protective factor against osteoporosis (OR = 0.79[0.71-0.88], P-value<0.001) and osteopenia (OR = 0.88[0.82-0.95], P-value<0.001). Eighteen serum metabolites were associated with both BMI change and T-score. Specifically, high-density lipoprotein (HDL) substructures demonstrated negative correlations (ß = -0.08 to -0.06 and - 0.12 to -0.08, respectively), while very low-density lipoprotein (VLDL) substructions showed positive correlations (ß = 0.09 to 0.10 and 0.10 to 0.11, respectively). The two lipid factors (HDL and VLDL) extracted by EFA acted as mediators between BMI change and T-score (Prop. Mediated = 8.16% and 10.51%, all P-value<0.01). CONCLUSION: BMI gain among Chinese aged 55-65 is beneficial for reducing the risk of osteoporosis. The metabolism of HDL and VLDL partially mediates the effect of BMI change on bone loss. Our research offers novel insights into the prevention of osteoporosis, approached from the perspective of weight management and lipid metabolomics.

Exosomes from hypoxic pretreated ADSCs attenuate ultraviolet light-induced skin injury via GLRX5 delivery and ferroptosis inhibition.

Accumulation studies have found that adipose-derived stem cell (ADSC) exosomes have anti-oxidant and anti-inflammatory characteristics. The current study verified their therapeutic potential to elucidate mechanisms of ADSC exosome actions in ultraviolet B (UVB) light-induced skin injury. Exosomes were isolated from ADSCs and hypoxic pretreated ADSCs. Next-generation sequencing (NGS) was applied to characterize differential mRNA expression. A UV-induced mice skin injury model was generated to investigate therapeutic effects regarding the exosomes via immunofluorescence and ELISA analysis. Regulatory mechanisms were illustrated using luciferase report analysis and in vitro experiments. The results demonstrated that exosomes from hypoxic pretreated ADSCs (HExos) inhibited UVB light-induced vascular injury by reversing reactive oxygen species, inflammatory factor expression and excessive collagen degradation. NGS showed that HExos inhibits UV-induced skin damage via GLRX5 delivery, while GLRX5 downregulation inhibited the therapeutic effect of HExos on UV-induced skin damage. GLRX5 upregulation increased the protective Exo effect on UV-induced skin and EPC damage by inhibiting ferroptosis, inflammatory cytokine expression and excessive collagen degradation. Therefore, the data indicate that HExos attenuate UV light-induced skin injury via GLRX5 delivery and ferroptosis inhibition.

Grass carp Il-2 promotes neutrophil extracellular traps formation via inducing ROS production and autophagy in vitro.

Interleukin (IL)-2 has been reported to regulate neutrophil functions in humans, mice, pigs and chicken although it is a key regulator of T cells. Consistently, we found that grass carp (Ctenopharyngodon idellus) interleukin-2 (gcIl-2) is capable of modulating the antimicrobial activities of neutrophils via regulating granzyme B- and perforin-like gene expression in our previous study. In the present study, stimulation of gcIl-2 on neutrophil extracellular traps (NETs) formation in grass carp neutrophils was demonstrated by detecting free DNA release, histone H3 citrullination and morphological changes of the cells. Further investigation revealed that reactive oxygen species (ROS) production from NADPH oxidase but not mitochondria was involved in NETosis induced by gcIl-2. Aside from ROS, autophagy was disclosed to be indispensable for NETosis induced by gcIl-2. These converging lines of evidence suggested that fish Il-2 could induce NETs formation via NADPH oxidase-derived ROS- and autophagy-dependent pathways in fish species which is evolutionarily conserved with that in mammals. It is noteworthy that these two pathways did not interplay with each other in Il-2-stimulated NETosis. The mechanisms governing autophagy induced by Il-2 were also explored in the present study, showing that Il-2 modulated the action of high mobility group box 1 (HMGB1) protein to stimulate autophagy, leading to NETs formation in fish neutrophils. These results provided a new insight to the function of Il-2 in fish neutrophils, and a clue about the regulation of NETosis in the lower vertebrates.

Fast detection of hypobromous acid in cells and the water environment using a lysosome-targeted fluorescent probe.

A new fluorescent probe SWJT-23 with lysosomal targeting ability for detection of hypobromous acid (HBrO) was synthesised based on the naphthalimide skeleton. This probe exhibited a fast response (within 3s), a low detection limit (1.24 nM), excellent selectivity and a high fluorescence quantum yield (Φ = 0.490). Moreover, SWJT-23 not only realized the sensitive detection of HBrO in cells and water samples, but also was fabricated as a paper-based sensor. In consequence, SWJT-23 is expected to be an efficient and powerful tool for monitoring HBrO in organisms and the environment in realistic scenarios.

An AIE-active tetra-aryl imidazole-derived chemodosimeter for turn-on recognition of hydrazine and its bioimaging in living cells.

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.

*H migration-assisted MvK mechanism for efficient electrochemical NH3 synthesis over TM-TiNO.

The electrochemical NH3 synthesis on TiNO is proposed to follow the Mars-van Krevelen (MvK) mechanism, offering more favorable N2 adsorption and activation on the N vacancy (Nv) site, compared to the conventional associative mechanism. The regeneration cycle of Nv represents the rate-determining step in this process. This study investigates a series of TM (Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, and Pt)-TiNO to explore the *H migration (from TM to TiNO)-promoted Nv cycle. The screening results indicate that Ni-TiNO exhibits strong H2O decomposition for *H production with 0.242 eV and low *H migration resistance with 0.913 eV. Notably, *H migration from Ni to TiNO significantly reduces the Nv formation energy to 0.811 eV, compared to 1.387 eV on pure TiNO. Meanwhile, in the presence of *H, Nv formation takes precedence over Tiv and Ov. Lastly, electronic performance calculations reveal that the collaborative function provided by Ni and Nv enables highly stable and efficient NH3 synthesis. The *H migration-assisted MvK mechanism demonstrates effective catalytic cycle performance in electrochemical N2 fixation and may have potential applicability to other hydrogenation reactions utilizing water as a proton source.

NiRu-Mo2Ti2C3O2 as an efficient catalyst for alkaline hydrogen evolution reactions: the role of bimetallic site interactions in promoting Volmer-step kinetics.

The Volmer step in alkaline hydrogen evolution reactions (HERs), which supplies H* to the following steps by cleaving H-O-H bonds, is considered the rate-determining step of the overall reaction. The Volmer step involves water dissociation and adsorbed hydroxyl (*OH) desorption; Ru-based catalysts display a compelling water dissociation process in an alkaline HER. Unfortunately, the strong affinity of Ru for *OH blocks the active sites, resulting in unsatisfactory performance during HER processes. Hence, this study investigates a series of key descriptors (ΔG*H2O, ΔG*H-OH, ΔG*H, and ΔG*OH) of TM (Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, or Pt)-Ru/Mo2Ti2C3O2 to systematically explore the effects of bimetallic site interactions on the kinetics of the Volmer step. The results indicate that bimetallic catalysts effectively reduced the strong adsorption of *OH on Ru sites; especially, the NiRu diatomic state shows the highest electron-donating ability, which promoted the smooth migration of *OH from Ru sites to Ni sites. Therefore, Ru, Ni and MXenes are suitable to serve as water adsorption and dissociation sites, *OH desorption sites, and H2 release sites, respectively. Ultimately, NiRu/Mo2Ti2C3O2 promotes Volmer kinetics and has the potential to improve alkaline HERs. This work provides theoretical support for the construction of synergistic MXene-based diatomic catalysts and their wide application in the field of alkaline HERs.

Effects of different HIIT protocols on exercise performance, metabolic adaptation, and fat loss in middle-aged and older adults with overweight.

Introduction: There is evidence that aging and obesity are associated with increased oxidative stress and chronic inflammation. High-intensity interval training (HIIT) may be superior to moderate-intensity continuous training (MICT) in anti-inflammatory and anti-obesity benefits. Therefore, the objective of this study is to determine which HIIT prescriptions will be more effective in reducing fat accumulation, inflammation, and improving metabolic adaptation and exercise performance in middle-aged and older overweight adults. Methods: Thirty-six middle-aged with overweight adults were divided into one of three groups: 1. L-HIIT group: the long-interval HIIT group (4 × 4 min Exercise/4 min Rest), 2. M-HIIT group: the medium-interval HIIT group (8 × 2 min Exercise/2 min Rest), 3. Control group: no exercise training intervention. All groups underwent the training stage for eight weeks (three sessions per week), followed by a detraining stage of four weeks in order to investigate the effects induced by different HIIT interventions on inflammation, metabolic adaptation, anti-fatigue and exercise performance, and fat loss Results: There was a significant physiological response in the change rate of heart rate (HR) after an acute L-HIIT session compared with an acute M-HIIT session (ΔHR: ↑49.66±16.09% vs ↑33.22±14.37%, p=0.02); furthermore, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly following a single L-HIIT session. After an eight-week training stage, the L-HIIT and M-HIIT groups exhibited a significant increase in aerobic capacity (ΔVO2peak), with values of +27.93±16.79% (p<0.001) and +18.39±8.12% (p<0.001), respectively, in comparison to the control group. Furthermore, in the L-HIIT group, the anaerobic power of relative mean power (RMP) exhibited a significant increase (p=0.019). However, following a four-week detraining stage, the adiponectin concentration remained 1.78 times higher in the L-HIIT group than in the control group (p=0.033). The results of blood sugar, blood lipids, body composition, and inflammatory markers did not indicate any improved it did not indicate any improvements from the two different HIIT protocols. Conclusions: The results indicate that an eight-week L-HIIT or M-HIIT intervention (three sessions per week, 32 minutes per session) may be an effective approach for improving aerobic capacity. It can be posited that L-HIIT may be a more advantageous mode than M-HIIT for enhancing anaerobic power, adipokine levels, and improving blood pressure in an aged and overweight population due to the induced physiological responses.

Combined microfocused ultrasound and delicate pulsed light for facial rejuvenation: A prospective, randomized, and split-face study.

OBJECTIVES: Public's interest in noninvasive skin rejuvenation treatments continues to grow. The advantage of combination therapy lies in that it can target different aspects of skin rejuvenation. This study aimed to assess the efficacy and safety of microfocused ultrasound (MFU) combined with delicate pulsed light (DPL) for facial rejuvenation. METHODS: Twenty-one patients with facial relaxation were enrolled. All patients received whole-face MFU treatment, and one side of the face was randomly assigned to receive DPL. MFU treatment was performed at Months 0 and 3, while DPL treatment was performed at Months 1, 2, 4, and 5. The length and angle of the nasolabial fold and perioral wrinkles, melanin index (MI), erythema index (EI), transepidermal water loss (TEWL), and follow-up time were recorded at Months 0, 3, and 6. Side effects were recorded during treatment and each follow-up visit. RESULTS: Twenty patients successfully completed the study. At the sixth month, the average length of perioral wrinkles and nasolabial folds on the combined side decreased by 11.5% (pwithin < 0.001) and 6.5% (pwithin = 0.011), while 8.3% (pwithin = 0.012) and 3.8% (pwithin = 0.02) on the MFU side. Compared with MFU treatment alone, the combined treatment also showed significant improvements in nasolabial fold angle (from 28.8 ± 3.4° to 32.7 ± 5.0°) and perioral wrinkle angle (from 39.3 ± 5.0° to 43.7 ± 5.1°). In addition, the combined side had greater benefits than the MFU side in improving MI, EI, TEWL, and skin elasticity (pbetween < 0.05). Except for one patient who withdrew due to increased skin sensitivity after MFU treatment, other subjects did not experience permanent or serious side effects. CONCLUSIONS: The combination of MFU and DPL for facial rejuvenation treatment is safe and effective. The combined treatment has better efficacy in skin firmness, and improving skin tone.

Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data.

BACKGROUND: Acute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons. METHODS: Herein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations. RESULTS: There were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04-1.28) and 1.07 (95% CI, 0.97-1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 µg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29-1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01-1.14), 1.19 (95% CI, 1.11-1.27), and 1.22 (95% CI, 1.13-1.32) for ILI + A/H1N1, A/H3N2, and B, respectively. CONCLUSIONS: Our findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.

Social anxiety and loneliness among older adults: a moderated mediation model.

BACKGROUND: Few studies have clarified the mechanisms linking social anxiety and loneliness in older populations. The study aimed to explore how social network mediate the relationship between social anxiety and loneliness in older adults, with perceived social support playing a moderating role. METHODS: A total of 454 older patients completed the Social Avoidance and Distress Scale, Lubben Social Network Scale-6, Chinese version of the Short Loneliness Scale and Perceived Social Support Scale. Bootstrap and simple slope methods were used to test the moderated mediation model. RESULTS: Social anxiety had a significant positive predictive effect on loneliness and social network partially mediated this relationship. The relationship between social anxiety and social network, as well as the relationship between social network and loneliness, was moderated by perceived social support. Specifically, perceived social support buffered the effects of social anxiety on social network, but the buffering effect diminished with increasing levels of social anxiety. On the social network and loneliness pathway, the social network of older persons with higher perceived social support has a stronger prediction of loneliness. CONCLUSIONS: The study found that social anxiety can contribute to loneliness by narrowing older adults' social network. High perceived social support can buffer this process, but do not overstate its protective effects. Thus, interventions to reduce social anxiety and improve social network and social support may help prevent and alleviate loneliness in older adults.