Analysis of the chain mediation effect between intergenerational support and mental health of older adults in urban China: a structural equation model.

BACKGROUND: This study aimed investigate the impact of intergenerational support on the mental health of older adults in urban China. It also sought to evaluate the chain mediation effect of attitudes toward younger people and willingness to interact with younger people within a non-familial context between intergenerational support and mental health. METHODS: Data were derived from a community survey that adopted quota sampling in mainland China in 2022 (N = 780). Structural equation modeling was used to analyze the data, and the bootstrap technique was used to test the mediation effect. RESULTS: A significant positive association was found between intergenerational support and the mental health of older adults in urban China (B = 0.852, 95% confidence interval CI [0.157,1.617]). Intergenerational support had a specific indirect effect on mental health through older adults' attitudes toward younger people within a non-familial context (B = 0.665, 95% CI [0.443,1.046]). There was a chain mediation effect (B = 0.126, 95% CI [0.069,0.224]) in relation to attitudes toward younger people and the willingness to interact with younger people between intergenerational support and mental health. Mediation accounted for 44.44% of the total effects in the model. CONCLUSION: These findings help identify modifiable factors that can improve the mental health of older adults. In line with the proposed serial multiple mediation model, this study provides theoretical and practical insights concerning the synergistic effect of intergenerational support at the family level and intergenerational interaction at the community level. Policy and social service implications are also discussed.

Mechanically Strong and Tough Poly(urea-urethane) Thermosets Capable of Being Degraded under Mild Condition.

The development of degradable polymeric materials such as degradable polyurethane or polyurea has been much highlighted for resource conservation and environmental protection. Herein, a facile strategy of constructing mechanically strong and tough poly(urea-urethane) (PUU) thermosets that can be degraded under mild conditions by using triple boron-urethane bonds (TBUB) as cross-linkers is demonstrated. By tailoring the molecular weight of the soft segment of the prepolymers, the mechanical performance can be finely controlled. Based on the cross-linking of TBUB units and hydrogen-binding interactions between TBUB linkages, the as-prepared PUU thermosets have excellent mechanical strength of ≈40.2 MPa and toughness of ≈304.9 MJ m-3 . Typically, the PBUU900 strip can lift a barbell with 60 000 times its own weight, showing excellent load-bearing capacity. Meanwhile, owing to the covalent cross-linking of TBUB units, all the PUU thermosets show initial decomposition temperatures over 290 °C, which are comparable to those of the traditional thermosets. Moreover, the TBUB cross-linked PUU thermosets can be easily degraded in a mild acid solution. The small pieces of the PBUU sample can be fully decomposed in 1 m HCl/THF solution for 3.5 h at room temperature.

Hybrid ultrathin-silicon/graphene waveguide photodetector with a loop mirror reflector.

Graphene has emerged as a promising solution for on-chip ultrafast photodetection for its advantages of easy integration, high mobility, adjustable chemical potential, and wide operation wavelength range. In order to realize high-performance photodetectors, it is very important to achieve efficient light absorption in the active region. In this work, a compact and high-speed hybrid silicon/graphene photodetector is proposed and demonstrated by utilizing an ultra-thin silicon photonic waveguide integrated with a loop mirror. With this design, the graphene absorption rate for the fundamental mode of TE polarization is improved by ∼5 times compared to that in the conventional hybrid silicon/graphene waveguide with hco=220 nm. One can achieve 80% light absorption ratio within the active-region length of only 20 µm for the present silicon/graphene waveguide photodetector at 1550 nm. For the fabricated device, the responsivity is about 25 mA/W under 0.3V bias voltage and the 3-dB bandwidth is about 17 GHz. It is expected to achieve very high bandwidth by introducing high-quality Al2O3 insulator layers and reducing the graphene channel length in the future.

Ultra-dense dual-polarization waveguide superlattices on silicon.

A dual-polarization waveguide superlattice is designed and realized by using 340 nm-thick silicon photonic waveguides. The silicon waveguide superlattices are formed with periodically arranged waveguides. Each period consists of five optical waveguides with core-widths designed optimally for minimizing the crosstalk among the optical waveguides. The optimized core-widths are 390 nm, 320 nm, 260 nm, 360 nm, and 300 nm when the separation between two adjacent waveguides is as small as 0.8 µm. With this design, the silicon waveguide superlattice works with low crosstalk (nearly -18 dB or less) for both polarizations within the range of 1530 nm to 1560 nm, which agrees well with the theoretical analysis.

Erythrocyte Membrane-Camouflaged IR780 and DTX Coloading Polymeric Nanoparticles for Imaging-Guided Cancer Photo-Chemo Combination Therapy.

Conventional systemic chemotherapy leads to poor therapeutic outcomes at moments in cancer therapy because the nontargeting anticancer drug release results in adverse effects and consequently drug resistance. The combination therapeutic strategy provides an alternative way to solve the conundrums. Herein, drug delivery systems with a rational design and tumor-targeting abilities become the ideal carriers for combinatorial therapy. IR780 iodide possesses near-infrared fluorescence intensity for fluorescence imaging (FI) and photothermal conversion for photoacoustic imaging (PAI), which also can be employed for tumor phototherapy (including photothermal therapy and photodynamic therapy). However, hydrophobicity and rapid elimination in vivo limit its biomedical applications. Furthermore, the hydrophobicity and high crystallization of IR780 result in poor drug-loading capacity and low stability. In this study, the high-pressure homogenization method was utilized for hydrophobic molecular IR780 and DTX coloading to construct IR780/DTX-PCEC nanoparticles which exhibit narrow size distribution and satisfactory drug-loading capacity. With further erythrocyte membrane [red blood cell (RBC)] camouflaging, the obtained IR780/DTX-PCEC@RBC nanoparticles present desired stability and prolonged circulation time in vivo. Additionally, the IR780/DTX-PCEC@RBC nanoparticles not only can be employed as a FI/PAI dual model imaging probe but also exhibit the property for phototherapy and chemotherapy of tumors. Based on the therapeutic outcome of combination therapy, the IR780/DTX-PCEC@RBC nanoparticles can serve as promising FI- and PAI-guided photo-chemo combination therapy agents for the future treatment of breast cancer.

Salmonella serotype determination utilizing high-throughput genome sequencing data.

Serotyping forms the basis of national and international surveillance networks for Salmonella, one of the most prevalent foodborne pathogens worldwide (1-3). Public health microbiology is currently being transformed by whole-genome sequencing (WGS), which opens the door to serotype determination using WGS data. SeqSero (www.denglab.info/SeqSero) is a novel Web-based tool for determining Salmonella serotypes using high-throughput genome sequencing data. SeqSero is based on curated databases of Salmonella serotype determinants (rfb gene cluster, fliC and fljB alleles) and is predicted to determine serotype rapidly and accurately for nearly the full spectrum of Salmonella serotypes (more than 2,300 serotypes), from both raw sequencing reads and genome assemblies. The performance of SeqSero was evaluated by testing (i) raw reads from genomes of 308 Salmonella isolates of known serotype; (ii) raw reads from genomes of 3,306 Salmonella isolates sequenced and made publicly available by GenomeTrakr, a U.S. national monitoring network operated by the Food and Drug Administration; and (iii) 354 other publicly available draft or complete Salmonella genomes. We also demonstrated Salmonella serotype determination from raw sequencing reads of fecal metagenomes from mice orally infected with this pathogen. SeqSero can help to maintain the well-established utility of Salmonella serotyping when integrated into a platform of WGS-based pathogen subtyping and characterization.

Self-Assembled Nanodelivery System with Rapamycin and Curcumin for Combined Photo-Chemotherapy of Breast Cancer.

Nanodelivery systems combining photothermal therapy (PTT) and chemotherapy (CT), have been widely used to improve the efficacy and biosafety of chemotherapeutic agents in cancer. In this work, we constructed a self-assembled nanodelivery system, formed by the assembling of photosensitizer (IR820), rapamycin (RAPA), and curcumin (CUR) into IR820-RAPA/CUR NPs, to realize photothermal therapy and chemotherapy for breast cancer. The IR820-RAPA/CUR NPs displayed a regular sphere, with a narrow particle size distribution, a high drug loading capacity, and good stability and pH response. Compared with free RAPA or free CUR, the nanoparticles showed a superior inhibitory effect on 4T1 cells in vitro. The IR820-RAPA/CUR NP treatment displayed an enhanced inhibitory effect on tumor growth in 4T1 tumor-bearing mice, compared to free drugs in vivo. In addition, PTT could provide mild hyperthermia (46.0 °C) for 4T1 tumor-bearing mice, and basically achieve tumor ablation, which is beneficial to improving the efficacy of chemotherapeutic drugs and avoiding damage to the surrounding normal tissue. The self-assembled nanodelivery system provides a promising strategy for coordinating photothermal therapy and chemotherapy to treat breast cancer.

Nanoformulations of small molecule protein tyrosine kinases inhibitors potentiate targeted cancer therapy.

Protein tyrosine kinases (PTKs) are closely related to tumor development and usually participate in apoptosis, DNA repair, and cell proliferation by activating signaling pathways. Therefore, PTKs have become the most promising targets for cancer therapy. In recent years, a large number of studies on the mechanism of tyrosine kinase activation have indicated that tyrosine kinase inhibitors (TKIs) have important clinical significance and application prospects as targeted anticancer drugs because they can effectively block certain cellular signaling pathways, inhibit tumor metastases and reduce tumor proliferation. Although the increasing emergence of anticancer drug resistance limits the clinical application of TKIs, emerging nanotechnology has made it possible to solve this problem. In this work, the state-of-art of small molecule protein tyrosine kinase inhibitors and the applications of drug delivery systems for TKIs are reviewed, and the potentials and challenges for future research of small molecule TKIs are addressed.

Nanogel: A Versatile Nano-Delivery System for Biomedical Applications.

Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, within their 3D polymer network. The nanosized nature of the carriers endows them with a specific surface area and inner space, increasing the stability of loaded drugs and prolonging their circulation time. Reactions or the cleavage of chemical bonds in the structure of drug-loaded nanogels have been shown to trigger the controlled or sustained drug release. Through the design of specific chemical structures and different methods of production, nanogels can realize diverse responsiveness (temperature-sensitive, pH-sensitive and redox-sensitive), and enable the stimuli-responsive release of drugs in the microenvironments of various diseases. To improve therapeutic outcomes and increase the precision of therapy, nanogels can be modified by specific ligands to achieve active targeting and enhance the drug accumulation in disease sites. Moreover, the biomembrane-camouflaged nanogels exhibit additional intelligent targeted delivery features. Consequently, the targeted delivery of therapeutic agents, as well as the combinational therapy strategy, result in the improved efficacy of disease treatments, though the introduction of a multifunctional nanogel-based drug delivery system.

High-performance silicon-graphene hybrid plasmonic waveguide photodetectors beyond 1.55 µm.

Graphene has attracted much attention for the realization of high-speed photodetection for silicon photonics over a wide wavelength range. However, the reported fast graphene photodetectors mainly operate in the 1.55 µm wavelength band. In this work, we propose and realize high-performance waveguide photodetectors based on bolometric/photoconductive effects by introducing an ultrathin wide silicon-graphene hybrid plasmonic waveguide, which enables efficient light absorption in graphene at 1.55 µm and beyond. When operating at 2 µm, the present photodetector has a responsivity of ~70 mA/W and a setup-limited 3 dB bandwidth of >20 GHz. When operating at 1.55 µm, the present photodetector also works very well with a broad 3 dB bandwidth of >40 GHz (setup-limited) and a high responsivity of ~0.4 A/W even with a low bias voltage of -0.3 V. This work paves the way for achieving high-responsivity and high-speed silicon-graphene waveguide photodetection in the near/mid-infrared ranges, which has applications in optical communications, nonlinear photonics, and on-chip sensing.

Hybrid manganese dioxide-bovine serum albumin nanostructure incorporated with doxorubicin and IR780 for enhanced breast cancer chemo-photothermal therapy.

The therapeutic outcome of chemotherapy is limited, although it is still the preferent strategy for cancer therapy. By regulation of tumor microenvironment and introduction of another therapeutic manner for combination therapy can enhance the anticancer activity of chemotherapeutics. Herein, we have constructed a hybrid nanostructure which composed of manganese dioxide (MnO2) and doxorubicin (DOX) as well as IR780 by stabilizing with BSA (BMDI) in one-pot procedure to alleviate tumor hypoxia and enhance tumor growth inhibition. The MnO2 can react with H2O2 to generate oxygen, and additionally react with GSH to realize tumor microenvironment responsive drug controlled release. And the release Mn ions further enhanced the magnetic resonance signal which made the BMDI a promising contrast agent for MRI. Moreover, the introduction of MnO2 has enhanced the anticancer activity of DOX in vitro and in vivo, and efficiently suppressed the tumor growth. By further introducing with photothermal therapy (PTT), the tumor growth was almost inhibited. It demonstrated that the BMDI hybrid nanostructure has great potential in tumor growth inhibition as therapeutics carrier.

Silicon-graphene conductive photodetector with ultra-high responsivity.

Graphene is attractive for realizing optoelectronic devices, including photodetectors because of the unique advantages. It can easily co-work with other semiconductors to form a Schottky junction, in which the photo-carrier generated by light absorption in the semiconductor might be transported to the graphene layer efficiently by the build-in field. It changes the graphene conduction greatly and provides the possibility of realizing a graphene-based conductive-mode photodetector. Here we design and demonstrate a silicon-graphene conductive photodetector with improved responsivity and response speed. An electrical-circuit model is established and the graphene-sheet pattern is designed optimally for maximizing the responsivity. The fabricated silicon-graphene conductive photodetector shows a responsivity of up to ~105 A/W at room temperature (27 °C) and the response time is as short as ~30 µs. The temperature dependence of the silicon-graphene conductive photodetector is studied for the first time. It is shown that the silicon-graphene conductive photodetector has ultra-high responsivity when operating at low temperature, which provides the possibility to detect extremely weak optical power. For example, the device can detect an input optical power as low as 6.2 pW with the responsivity as high as 2.4 × 107 A/W when operating at -25 °C in our experiment.

Brucella suis Vaccine Strain 2 Induces Endoplasmic Reticulum Stress that Affects Intracellular Replication in Goat Trophoblast Cells In vitro.

Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER), and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2) in goat trophoblast cells (GTCs) and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm), a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA), a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR) chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist) in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.

Brucella suis vaccine strain S2-infected immortalized caprine endometrial epithelial cell lines induce non-apoptotic ER-stress.

Brucella, which is regarded as an intracellular pathogen responsible for a zoonotic disease called brucellosis, survives and proliferates within several types of phagocytic and non-phagocytic cells. Brucella infects not only their preferred hosts but also other domestic and wild animal species, inducing abortion and infertility. Therefore, the interaction between uterine cells and Brucella is important for understanding the pathogenesis of this disease. In this study, we describe the Brucella suis vaccine strain S2 (B.suis.S2) infection and replication in the immortalized caprine endometrial epithelial cell line hTERT-EECs and the induced cellular and molecular response modulation in vitro. We found that B.suis S2 was able to infect and replicate to high titers and inhibit the proliferation of EECs and induce non-apoptotic pathways, as determined by B.suis.S2 detection using MTT and acridine orange/ethidium bromide (AO/EB) staining and flow cytometry. We explored the evidence of non-apoptotic pathways using real-time quantitative RT-PCR and by western blot analysis. Finally, we discovered the over-expression of GRP78, ATF4, ATF6, PERK, eIF2α, CHOP, and cytochrome c (Cyt-c) but not IRE1, xbp-1, and caspase-3 in B.suis.S2 (HK)-attacked and B.suis.S2-infected cells, suggesting that the molecular mechanism of ER stress sensor activation by B.suis.S2 is basically concomitant with that by B.suis.S2 (HK) and that ER stress, especially the PERK pathway, plays an important role in the process of B.suis.S2 infecting EEC, which may, in part, explain the role of the uterus in the pathogenesis of B.suis.S2.