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Background: Little is known about the effects of maintaining healthy sleep patterns on frailty transitions. Methods: Based on 23,847 Chinese adults aged 30–79 in a prospective cohort study, we examined the associations between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions. Results: During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89–0.96), 0.76 (0.74–0.77), and 0.85 (0.82–0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00–1.18) and 1.42 (1.31–1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend Conclusions: Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.

Objective: To identify the causative adenomatous polyposis coli (APC) gene defects associated with a pedigree of familial adenomatous polyposis (FAP). Methods: FAP was diagnosed based on clinical manifestations, family history, as well as endoscopic and pathological examinations. The blood samples of the FAP pedigree members, colonic polyp patients, and normal individuals were collected. Genomic DNA was then extracted from those samples. APC mutation analysis was conducted via direct polymerase chain reaction (PCR) sequencing. Results: Three synonymous mutations and a missense mutation were found: c.5034G>A (p.Gly1678Gly), c.5465T>A (p.Val1822Asp), c.5880G>A (p.Pro1960Pro), and c.5274T>G (p.Ser1758Ser). Among them, the homozygous mutation on APC gene c.5034G>A has been reported, while the other three mutations have not been reported in the Chinese Han population. Individuals with c.5465T>A (p.Val1822ASP) missense mutation eventually suffer from colon cancer and have poor prognosis. We found no mutation in patients with simple intestinal polyp and in normal individuals. In addition, there were homozygous and heterozygous mutations in different patients from the same family. Conclusion: Three new mutations of APC gene were firstly reported in Han population. The missense mutation of c.5465T>A (p.Val1822Asp) may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.

Pre-eclampsia (PE) is characterized by maternal hypertension and/or proteinuria after 20 weeks of gestation. Shallow trophoblast invasion into spiral artery (SpA) and defective decidualization have been implicated in the pathogenesis of PE. However, the underlying mechanisms remain unclear. AXL receptor tyrosine kinase is a biomarker and therapeutic target for a variety of metastatic cancers while tumorigenesis and placentation share many features. In this study, a new function of AXL in promoting SpA remodeling and trophoblast invasion were demonstrated. The pregnantAxlknockout (Axl−/−) mice exhibited typical PE symptoms, including increased blood pressure and proteinuria. Artificially induced decidualization experiments showed that appeared normal, however, RNA-seq results ofAxl−/−deciduoma revealed abnormal expression of a number of transcripts, includingCorin, which encodes a cardiac protease that activates atrial natriuretic peptide (ANP). Treatment with ANP reversed the PE symptoms. Moreover, in decidua from women afflicted with PE, AXL level was significantly lower than that in normal pregnancies. These data show that the abnormality of decidua-derived AXL-CORIN-ANP affects maternal-fetal crosstalk and contributes to PE.

In this study, Ag0.23/(S1.66-N1.91/TiO2-x) single-atom photocatalyst was synthesized by in-situ photo-reducing of silver on S,N-TiO2-x nanocomposite and used to degrade bisphenol A (BPA) through heterogeneous activation of potassium peroxymonosulfate (PMS) under visible-light illumination. The structure, physicochemical property, morphology, and electronic property were evalutated by X-ray diffraction (XRD), Raman spectrum, X-ray photoelectron spectra (XPS), high-resolution transmission electron microscopy (HR-TEM), UV–vis diffuse reflectance spectra (UV-vis DRS), electron paramagnetic resonance (EPR) spectrum. Ag0.23/(S1.66-N1.91/TiO2-x) single-atom photocatalyst exhibited 2.4 times higher activity for the synergetic degradation of BPA than that of its counterpart, and 48.73% mineralization rate of BPA also achieved. It was ascribed to the uniformly-dispersed metallic Ag atoms as the active site for accelerating the migration rate of photo-generated carrier for generation of high reactive radicals. The EPR experiments indicated that SO4•‒ and •OH was jointly involved in BPA degradation.

A novel Pt/Ru–Ir oxide catalyst has been successfully synthesized for efficient anodic destruction of perfluorooctanoic acid, a refractory organic pollutant with significant environmental and human health concerns.

Homopolypeptide poly(γ-benzyl-l-glutamate) can self-assemble into fluorescent toroids following an end-to-end closure mechanism.

Diabetic wounds are difficult to heal due to recurrent bacterial infection, decreased proliferation, and migration of epidermal and endothelial cells. This is related to impaired leukocyte function...

Self-amplifying RNA (saRNA) is a next-generation vaccine platform, but like all nucleic acids, requires a delivery vehicle to promote cellular uptake and protect the saRNA from degradation. To date, delivery platforms for saRNA have included lipid nanoparticles (LNP), polyplexes and cationic nanoemulsions; of these LNP are the most clinically advanced with the recent FDA approval of COVID-19 based-modified mRNA vaccines. While the effect of RNA on vaccine immunogenicity is well studied, the role of biomaterials in saRNA vaccine effectiveness is under investigated. Here, we tested saRNA formulated with either pABOL, a bioreducible polymer, or LNP, and characterized the protein expression and vaccine immunogenicity of both platforms. We observed that pABOL-formulated saRNA resulted in a higher magnitude of protein expression, but that the LNP formulations were overall more immunogenic. Furthermore, we observed that both the helper phospholipid and route of administration (intramuscular versus intranasal) of LNP impacted the vaccine immunogenicity of two model antigens (influenza hemagglutinin and SARS-CoV-2 spike protein). We observed that LNP administered intramuscularly, but not pABOL or LNP administered intranasally, resulted in increased acute interleukin-6 expression after vaccination. Overall, these results indicate that delivery systems and routes of administration may fulfill different delivery niches within the field of saRNA genetic medicines., Graphical abstract Unlabelled Image

Dented nanospheres show promising potential in drug delivery, nanomotors, etc. However, it is still challenging to prepare them by homopolymer self-assembly because of the strict structural requirements of the homopolymer. Herein, we propose a strategy for preparing dented nanospheres from homopolymers by co-assembly with a short peptide. They were co-assembled from poly(2-hydroxy-3-((4-(ethoxycarbonyl)phenyl)amino)propyl methacrylate) (PHBzoMA59) and (S)-2-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropanamido)-3-phenylpropanoic acid (Fmoc-FF-OH). PHBzoMA homopolymers can only self-assemble into nanospheres without dent, and the addition of a short peptide introduced hydrogen bonding and complementary π-π stacking interactions led to the final dented nanosphere morphology. The weight fractions of the short peptide can be adjusted to regulate the final morphology. It was confirmed that the radius of curvature of the dent on the surface was related to the organic bubble inside the protospheres prepared at critical aggregation concentration (CAC). The organic bubble can be adjusted by altering the kind of organic solvent and solution pH, which allowed control over the dented nanosphere dimension. The use of different organic solvents with various polarities allows adjustment of the interfacial tension, and hence the denting degree. This degree can also be controlled by manipulating the solution pH to (de)protonate the short peptide and homopolymer. Furthermore, the versatility of this method was highlighted by using a different homopolymer and the applicability of the resulting dented nanospheres was demonstrated by decoration with gold nanoparticles. Overall, this study provided important insights and a new simple strategy to prepare dented nanospheres in a controlled fashion.

Background: More than one-fifth of the world’s population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. Methods: A multicenter, patient- and outcome assessor–blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. Results: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was –5.0 (95% CI, –6.5 to –3.5) mm Hg and –2.8 (95% CI, –3.7 to –1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were –10.0 (95% CI, –12.1 to –7.9) mm Hg and –3.8 (95% CI, –5.0 to –2.5) mm Hg, respectively. The effect size did not differ among cuisines ( P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, –0.1 to 0.2; P =0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups ( P =0.259), and none of the adverse events was associated with the intervention. Conclusions: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03882645.

Antibacterial polypeptides as ancient immune defense systems are effective against bacteria. Here we report a novel kind of “armed” carrier: an antibacterial polypeptide-grafted chitosan-based nanocapsule with an excellent antibacterial efficacy against both Gram-positive and Gram-negative bacteria. This nanocapsule also has excellent blood compatibility and low cytotoxicity. Patients after tumor surgery may benefit from this “armed” carrier because it is highly anti-inflammation and is able to deliver anticancer and antiepileptic drugs simultaneously.

Hierarchical self-assembly offers great possibilities to mimic biological systems with finely arranged complex structures. Herein, we demonstrate the preparation and formation mechanism of an unusual giant polymer vesicle with a latticelike membrane (GVLM). This GVLM is formed by fusion-induced particle assembly (FIPA) of small vesicles that are self-assembled from poly(ethylene oxide)

Placentation and tumorigenesis have many common features. Human placentation builds a maternal–fetal connection, circumvents maternal immune rejection of the fetus, and utilizes mechanisms that support tumorigenesis, such as proliferation, invasion, angiogenesis, and immune tolerance. Trophoblasts of the human placenta mimic the behavior of malignant cells, proliferating and invading the uterine decidua until reaching the myometrium and remodeling the spiral arteries that establish a new vascular system and escape the maternal immune response. These processes are under precise temporal and spatial regulation, and their dysregulation is associated with different pregnancy syndromes, including preeclampsia (PE), a pregnancy syndrome that is the leading cause of maternal and perinatal mortality and morbidity. At present, the precise mechanisms underlying the development of PE remain unclear. Here, we summarize and dissect the features between physiological placentation and pathological tumorigenesis to explore the pathogenesis of PE – which we believe to be the result of insufficient placentation, compared to the overaggression of tumorigenesis – to provide novel strategies to prevent and treat PE.

Pre-eclampsia (PE) is a pregnancy-related disorder that occurs after 20 weeks of gestation. It seriously affects the health of maternity and the fetus. However, the pathogenesis of PE is still unknown. Decidualization deficiency is considered a contributing factor to the development of PE. CTP synthetase (CTPS) which is the rate-limiting enzyme in the CTP de novo biosynthesis, is essential for nucleic acid synthesis and cellular energy metabolism, and often appears as cytoophidium in many cell types. Here, we found that the expression of CTPS was significantly downregulated in decidual tissues of patients with severe PE compared with healthy pregnant women. During in vitro decidualization, changes in CTPS were accompanied by opposite fluctuation of the AMPK signaling pathway. Moreover, the downregulation of CTPS by glutamine analogs or CTPS small interfering RNA inhibited the decidualization process and the AMPK signaling pathway. Investigating the underlying mechanism of action by co-immunoprecipitation coupled with mass spectrometry showed that CTPS interacted with ATP synthase (ATPS) and maintained the content of ATP on Day 3 of decidualization. However, when combined with mitochondrial stress protein STRESS-70 instead of ATPS, the concentration of ATP on Day 6 of induction was reduced. Corresponding to this, CTPS was mainly distributes in the cytoplasm on Day 3 of induction, while it appeared both in the cytoplasm and the nucleus on Day 6 in decidualized cells, which was similar to that in cells before induction. In summary, we believe that CTPS plays an important role in decidualization by participating in energy metabolism. Abnormal expression of CTPS in decidualization would lead to abnormal decidualization and consequently result in the occurrence of PE.

Aging population has been boosting the need for orthopedic implants. However, biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine

Electrocatalytic oxidation is regarded as an effective technique for decomposing refractory organic compounds like perfluorooctanoic acid (PFOA). However, achieving highly efficient and long-life electrodes is still a great challenge. Herein, Ti/RuO

One major side effect of chemotherapy that young women with cancer suffer from is ovarian damage. Therefore, it is necessary to study the pathogenesis of chemotherapeutic drugs in order to develop pharmaceutical agents to preserve fertility. Epirubicin is one of the commonly used chemotherapy drugs for breast cancer patients. This research explored the side effects of epirubicin in mice. We found that epirubicin significantly reduced the body weight, the weight of the ovaries and uteri, and the pups' number, while melatonin, which is extremely resistant to oxidation, significantly reduced these damages. Moreover, co-treatment with melatonin prevented epirubicin-induced decrease in Einf2/infand progesterone, and the loss of follicles. Mechanism study showed that melatonin significantly reduced the levels of proapoptotic genes p53, Caspase3, and Caspase9 while it upregulated antiapoptotic factors Bcl-2 and Bcl2l1, and antioxidant genes superoxide dismutase 1 and catalase compared with the epirubicin group. In addition, melatonin markedly reduced reactive oxygen species (ROS) and the transcription of Caspase12 and Chop, which is vital in endoplasmic reticulum stress (ERS)-mediated apoptosis. These results indicate melatonin protects against epirubicin-induced ovarian damage by reducing ROS-induced ERS. Therefore, melatonin has a therapeutic potential for the protection of ovarian function and preservation of fertility during chemotherapy.

Controlling the compositions and morphologies of the electrocatalysts were conventionally used for improving the catalytic activities. Here, visible-light-enhanced electrocatalytic water reduction reactions on semimetal bismuth (Bi) nanorods were achieved. The Bi catalyst not only exhibited an ideal Faradaic efficiency of 98% for electrocatalytic hydrogen production, but also acted as a light absorber for improving the activity even under light irradiation up to 740 nm. As a result, the solar-to‑hydrogen conversion efficiency under simulated AM 1.5G illumination was reached to 0.82%, which is 2.7 times higher than that induced by plasmon Au nanoparticles. This conversion efficiency is attributed to the excellent solar light absorption property of Bi and the enhanced electron-transfer at the interface of Bi/electrolyte under irradiation. The low-cost Bi catalyst with the dual function could open a venue toward designing more-energy-efficient electrocatalysts for hydrogen production assisted by sunlight.

Transition metal single atoms (TM-SAs) coordinated with highly electronegative N atoms often suffer from low activity and poor stability, which limiting their application in catalysis. To solve it, a PH

RNA interference (RNAi) technology has great potential in cancer therapy, e.g., small interfering RNA (siRNA) can be exploited to silence specific oncogenes related to tumor growth and progression. However, it is critical to achieve high transfection efficiency while reducing cytotoxicity. In this paper, we report an siRNA delivery strategy targeting the oncogene KRAS based on arginine-modified poly(disulfide amine)/siRNA nanocomplexes. The poly(disulfide amine) is synthesized via aza-Michael polyaddition followed by the introduction of arginine groups onto its backbone to afford poly((N,N'-bis(acryloyl)cystamine-co-ethylenediamine)-g-Nω-p-tosyl-l-arginine) (PBR) polycations. Thus multiple interactions including electrostatic interaction, hydrogen bonding and a hydrophobic effect are introduced simultaneously between PBR and siRNA or cell membranes to improve transfection efficiency. By optimizing the grafting density of arginine groups, PBR/siRNA nanocomplexes achieve high cellular uptake efficiency, successful endosomal/lysosomal escape, and rapid biodegradation in the presence of high GSH concentration in the cytoplasm, and finally release siRNA to activate the RNAi mechanism. Additionally, compared to commercially available PEI 25K, PBR/siRNA nanocomplexes possess a significantly increased gene silencing effect on human pancreatic cancer cells (PANC-1) with decreased cytotoxicity and enhanced tumor penetration ability in PANC-1 multicellular spheroids in vitro. Overall, with both GSH-responsiveness and excellent tumor penetration, this safe and efficient poly(disulfide amine)-based siRNA delivery system is expected to provide a new strategy for gene therapy of pancreatic cancer and other stromal-rich tumors.

The application of tandem catalysis is rarely investigated in degrading organic pollutants in the environment. Herein, a tandem catalyst on single platinum (Pt) nanoparticles (Pt0 NPs) is prepared for the sequential degradation of formaldehyde (HCHO) to carbon dioxide gas [CO2(g)] at room temperature. The synthesis approach includes coating of uniform Pt NPs on SrBi2Ta2O9 platelets using a photoreduction process, followed by calcination of the sample in the atmosphere to tune partial transformation of Pt0 atoms to Pt2+ ions in the tandem catalyst. The conversion of HCHO to CO2(g) is monitored by in situ Fourier transform infrared spectroscopy, which shows first conversion of HCHO to CO32- ions onto Pt0 active sites and subsequently the conversion of CO32- ions to CO2(g) by neighboring Pt2+ species of the catalyst. The later process with Pt2+ species does not allow CO32- poisoning of the catalyst. The enhanced activity of the prepared tandem catalyst to oxidize HCHO is maintained continuously for 680 min. Comparatively, the catalyst without Pt2+ shows activity for only 40 min. Additionally, the tandem catalyst presented herein performs better than the Pt/titanium dioxide (TiO2) catalyst to degrade HCHO. Overall, the tandem catalyst may be applied to degrade organic pollutants efficiently.

The synthesis and aqueous self‐assembly of a new class of amphiphilic aliphatic polyesters are presented. These AB block polyesters comprise polycaprolactone (hydrophobe) and an alternating polyester from succinic acid and an ether‐substituted epoxide (hydrophile). They self‐assemble into biodegradable polymersomes capable of entering cells. Their degradation products are bioactive, giving rise to differentiated cellular responses inducing stromal cell proliferation and macrophage apoptosis. Both effects emerge only when the copolymers enter cells as polymersomes and their magnitudes are size dependent.

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator that has been characterized as master regulators of mitochondrial biogenesis. It has been reported that aberrant regulation of PGC-1α is involved in a variety of human cancers. However, whether PGC-1α is involved in the regulation of tumor growth and metastasis in gastric cancer (GC) remains unknown. In the present study, we found that the expression of PGC-1α was upregulated in GC tissues and GC cell lines. Inhibition of PGC-1α inhibited cell viability, migration, and invasion, and promoted cell apoptosis of GC cells. Furthermore, inhibition of PGC-1α downregulated the SNAI1 expression, whereas upregulated microRNA (miR)-128b expression. The expression of SNAI1 was upregulated and the expression of miR-128b was downregulated in GC tissues. We further found that there was a positive correlation between PGC-1α and SNAI1 expression, and a negative correlation between PGC-1α and miR-128b expression or between SNAI1 and miR-128b expression in GC tissues. Moreover, PGC-1α inhibition-induced increased miR-128b expression, and PGC-1α overexpression-induced decreased miR-128b expression were both markedly suppressed by SNAI1 overexpression. In addition, SNAI1 overexpression or miR-128b inhibition partly reversed the effects of PGC-1α inhibition in GC cells. Furthermore, inhibition of PGC-1α suppressed the tumor growth in a nude mouse model, which may be related with the dysregulation of SNAI1 and miR-128b. In conclusion, these data indicate that the PGC-1α/SNAI1/miR-128b axis plays a vital role in GC via regulating cell viability, migration, invasion, and apoptosis.

Graphitic carbon nitride (g-C3N4) with Pt co-catalyst was synthesized by in-situ photoreduction and used as a visible light photocatalyst. The size of Pt co-catalyst can be controlled form single atoms to nano-clusters by the induced amount of Pt precursor. The results indicated that compared with nano-clusters, the Pt0.1-CN (with 0.1 wt% Pt loading amount) which is characterized as single-atom Pt exhibits a pronounced photocatalytic hydrogen evolution capability. For Pt0.1-CN with single-atom Pt as co-catalyst, the H2 generation is up to 473.82 µmol mg−1pt under visible light irradiation (λ > 420 nm). The enhanced photocatalytic performance is mainly attributed to the synergistic effect of high light adsorption efficiency, effective charge separation, and high dispersed active sites of Pt atoms. The results of this work highlighted that loading g-C3N4 with Pt single atoms will achieve a maximum utilization efficiency of Pt atoms and an improvement photocatalytic performance.