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We show the generation of a tunable linearly chirped microwave waveform (LCMW) with an ultra-large time-bandwidth product (TBWP) based on a hybrid Fourier-domain mode-locked (FDML) laser. The key device in the hybrid FDML laser is a silicon photonic integrated micro-disk resonator (MDR) which functions as an optical bandpass filter, to have strong wavelength selectivity and fast frequency tunability. By incorporating the integrated MDR in the fiber-based ring cavity to perform frequency-domain mode locking, an FDML laser is realized and a broadband frequency-chirped optical pulse is generated. By beating the frequency-chirped optical pulse with an optical carrier from a laser diode (LD) at a photodetector (PD), an LCMW is generated. The bandwidth of the LCMW is over 50 GHz and the temporal duration is over 30 µs, with an ultra-large TBWP of 1.5 × 10 6 . Thanks to the strong tunability of the MDR in the FDML laser, the generated LCMW is fully tunable in terms of bandwidth, temporal duration, chirp rate, and center frequency. Linearly chirped microwave waveforms with high time-bandwidth products would have important applications but are difficult to achieve. Here the authors generate such a waveform in a photonic setting by implementing a micro-disk resonator as a tunable optical bandpass filter in a Fourier-domain mode-locked laser.

Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.This Review summarizes adaptive immune cell dysregulation in obesity and type 2 diabetes mellitus (T2DM). Under-appreciated comorbidities of obesity and T2DM (oral cavity inflammation, neuroinflammation and dysbiosis) are considered, and previous clinical trials of anti-inflammatory therapies for T2DM are discussed.

Flue-cured tobacco (FCT) with irritating and undesirable flavor must be aged. However, the spontaneous aging usually takes a very long time for the low efficiency. Bioaugmentation with functional strains is a promising method to reduce aging time and improve sensory quality. To eliminate the adverse effect of excessive starch or protein content on the FCT quality, we used the flow cytometry to sort Bacillus amyloliquefaciens LB with high alpha-amylase and Bacillus kochii SC with high neutral protease from the FCT microflora. The mono, co-culture of strains was performed the solid-state fermentation with FCT. Bacillus amyloliquefaciens monoculture for 2 days and Bacillus kochii monoculture for 2.5 days achieved the optimum quality. B. amyloliquefaciens – B. kochii co-culture at a ratio of 3:1 for 2 days of fermentation showed a more comprehensive quality enhancement and higher functional enzyme activity than mono-cultivation. Through OPLS-DA model (orthogonal partial least-squares-discriminant analyzes), there were 38 differential compounds between bioaugmentation samples. In co-cultivation, most of Maillard reaction products and terpenoid metabolites were at a higher level than other samples, which promoted an increase in aroma, softness and a decrease in irritation. This result validated the hypothesis of quality improvement via the co-culture. In our study, we presented a promising bioaugmentation technique for changing the sensory attributes of FCT in a short aging time.

Aromatic compounds constitute the primary chemical components responsible for the distinctive flavor characteristics of cigars and play a pivotal role in cigar quality assessment. This study employed solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC-MS) and liquid-liquid extraction/gas chromatography-mass spectrometry (LLE/GC-MS) to analyze the aroma profiles of Chinese and international cigars under smoking and simulated oral environment conditions. Based on multidimensional statistical and model evaluations—including One-way analysis of variance ( P  ≤ 0.05), odor activity threshold (OAV ≥ 1), variable importance in projection (VIP ≥ 2), and fold change (≥ 1.5)—six key aromatic compounds were identified as significant contributors to the characteristic flavor of Chinese cigars: methylpyrazine, tabanone, 3-methylbutyric acid, limonene, 2,6-dimethylphenol, and malic acid. To elucidate the sensory perception mechanisms of these compounds, molecular dynamics simulations were conducted to investigate interactions between the human oral cavity receptor T1R1 and the identified aromatic compounds. The results revealed that 2,6-dimethylphenol, 3-methylbutyric acid, malic acid, and methylpyrazine exhibited specific binding interactions with the T1R1 receptor. These molecular interactions are hypothesized to facilitate receptor-mediated perception of the compounds in the oral environment, thereby contributing to the overall sensory experience of Chinese cigar.

BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

In this paper, a novel one-pot strategy was utilized to immobilize gold nanorods (GNRs) onto the surface of PEGylated graphene oxide (GO-PEG) via polydopamine (PDA) to fabricate GNRs/GO@PDA hybrid nanosheets. The GNRs/GO@PDA nanosheets possessed excellent photostability and photothermal conversion efficiency (36.10%), due to the robust interfacial immobilization of PDA between GNRs and GO-PEG. Besides, GNRs/GO@PDA also could be utilized to be an efficient drug nano-vehicle that possessed an excellent loading ability for anticancer drug doxorubicin hydrochloride (DOX) (86.16%). Furthermore, the drug release of hybrid nanosheets could be triggered by pH value and near-infrared (NIR) light irradiation, which could be mainly ascribed to the strong π–π stacking interaction between GNRs/GO@PDA and DOX, as well as the brilliant NIR-responsive property of GNRs/GO@PDA. It was found that GNRs/GO@PDA possessed extremely low cytotoxicity to MCF-7 cells even at 250 μg mL−1, while GNRs/GO@PDA(DOX) showed obvious cytotoxicity at 100 μg mL−1. Thus, this paper presents a feasible strategy to fabricate GNRs/GO hybrid nanosheets with high drug loading capacity, excellent photothermal conversion property and pH/NIR-stimuli-responsive drug delivery performance, which possesses brilliant potentials to be an efficient platform for remotely triggered drug delivery.

Previous epidemiological studies on the relation between dietary legume consumption and risk of colorectal cancer (CRC) remain controversial. We conducted a meta-analysis based on prospective cohort studies to investigate the association between dietary legume consumption and risk of CRC. Fourteen cohort studies were finally included, containing a total of 1903459 participants and 12261 cases who contributed 11628960 person-years. We found that higher legume consumption was associated with a decreased risk of CRC (RR, relative risk = 0.91; 95% CI, confidence interval = 0.84–0.98). Subgroup analyses suggested that higher legume consumption was inversely associated with CRC risk in Asian (RR = 0.82; 95% CI = 0.74–0.91) and soybean intake was associated with a decreased risk of CRC (RR = 0.85; 95% CI = 0.73–0.99). Findings from our meta-analysis supported an association between higher intake of legume and a reduced risk of CRC. Further studies controlled for appropriate confounders are warranted to validate the associations.

Drug resistance is a major problem to overcome in the treatment of cancer; therefore, identifying therapeutic targets for drug resistance is a point of focus in the field of cancer research. Long non-coding RNAs (lncRNAs) and microRNAs (miRs) not only affect gene expression regulation during cell proliferation, but also have several potential roles in the drug resistance of malignant tumors. Reverse transcription-quantitative PCR was used to detect the expression levels of DDX11 antisense RNA 1 (DDX11-AS1) and miR-497 in MCF-7 and MDA-MB-231 cells. Cell transfection techniques were used to interfere with the expression levels of DDX11-AS1 and miR-497. Cell Counting Kit-8 and MTT assays were used to detect cell viability. A colony formation assay was used to detect cell proliferation. Wound-healing and Transwell assays were performed to measure the levels of cell migration and invasion. Western blotting was used to analyze the expression levels of migration-associated proteins, and immunofluorescence and western blotting were used to determine the expression levels of the epithelial-mesenchymal transition-related proteins E-cadherin and N-cadherin, respectively. A luciferase reporter gene assay was used to verify the targeted binding of DDX11-AS1 and miR-497. The present study demonstrated that the expression levels of lncRNA DDX11-AS1 were markedly increased in paclitaxel (PTX)-resistant breast cancer cell lines. By contrast, knockdown of DDX11-AS1 expression inhibited PTX resistance of breast cancer cells, and suppressed the proliferation, invasion and migration of breast cancer cells, which was achieved via upregulation of miR-497 expression. In conclusion, knockdown of lncRNA DDX11-AS1 could inhibit the proliferation, migration and PTX resistance of breast cancer cells by upregulating miR-497 expression.

Green technological innovation is crucial for the manufacturing industry's green transformation and sustainable development. This study examines the impact of executive overconfidence on corporate green innovation, focusing on the internal drivers of corporate innovation and using a sample of Shanghai and Shenzhen A-share listed manufacturing companies from 2013 to 2020. We further examine the mediating role of digital transformation and the moderating role of external attention. The findings indicate that executive overconfidence promotes corporate green technological innovation. Overconfident executives enhance green innovation by accelerating digital transformation. Moreover, external attention from analysts and media positively moderates the relationship between executive overconfidence and corporate green innovation. Heterogeneity analysis reveals that the positive impact of executive overconfidence on green innovation is more significant in non-state-owned enterprises, high-tech firms, and enterprises with lower pollution levels.

The aphid, Aphis gossypii Glover, and the leaf beetle, Lema decempunctata Gebler, are two catastrophic pests affecting the production of the organic goji berry, Lycium barbarum L. Our previous studies have demonstrated that the defense responses of goji berry induced by aphid infestations can facilitate the growth and development of beetles. However, the reciprocal effects of these two insect infestations on aphids remained unclear. In this study, the impacts of these two pest infestations on the development, survival, and reproduction of aphids were examined. Additionally, the levels of plant defense-related hormones, salicylic acid (SA) and jasmonic acid (JA), were measured. Subsequently, host plants were treated with two hormone analogues, 2, 1, 3-benzothiadiazole (BTH) and methyl jasmonate (Me-JA), to identify their effects on aphid development, survival, and reproduction. The results showed that the total developmental duration was accelerated by 33.60%, and the total reproduction of aphids was increased by 82.98% compared to the control after aphid infestation, without influencing survival. In contrast, the beetle infestation did not significantly influence any aspect of the aphid population. The content of SA in plants after the aphid infestation and JA after the beetle infestation increased 19.42 times and 400.50 times, respectively, compared with the control. The total developmental duration of aphids treated with BTH was reduced by 13.44%, while their reproduction increased by 60.52% compared with the control. The total developmental duration of aphids treated with Me-JA was prolonged by 23.51% compared to the control, while survival rates and reproduction were unchanged. Our research elucidates the intricate interspecific relationship between A. gossypii and L. decempunctata, providing valuable insights into the complex interspecific relationship between the two pests and informing effective strategies for their scientific prevention and control.