Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection.

Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.

Endothelial dysfunction (ED) is commonly considered a crucial initiating step in the pathogenesis of numerous cardiovascular diseases. The coupling of endothelial nitric oxide synthase (eNOS) is important in maintaining normal endothelial functions. However, it still remains elusive whether and how eNOS SUMOylation affects the eNOS coupling. In the study, we investigate the roles and possible action mechanisms of protein inhibitor of activated STAT 1 (PIAS1) in ED. Human umbilical vein endothelial cells (HUVECs) treated with palmitate acid (PA) in vitro and ApoE-/- mice fed with high-fat diet (HFD) in vivo were constructed as the ED models. Our in vivo data show that PIAS1 alleviates the dysfunction of vascular endothelium by increasing nitric oxide (NO) level, reducing malondialdehyde (MDA) level, and activating the phosphatidylinositol 3-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-AKT-eNOS) signaling in ApoE-/- mice. Our in vitro data also show that PIAS1 can SUMOylate eNOS under endogenous conditions; moreover, it antagonizes the eNOS uncoupling induced by PA. The findings demonstrate that PIAS1 alleviates the dysfunction of vascular endothelium by promoting the SUMOylation and inhibiting the uncoupling of eNOS, suggesting that PIAS1 would become an early predictor of atherosclerosis and a new potential target of the hyperlipidemia-related cardiovascular diseases.

Asprosin contributes to pathogenesis of obesity by adipocyte mitophagy induction to inhibit white adipose browning in mice.

BACKGROUND: Asprosin (ASP) is a newly discovered adipokine secreted by white adipose tissue (WAT), which can regulate the homeostasis of glucose and lipid metabolism. However, it is not clear whether it can regulate the browning of WAT and mitophagy during the browning process. Accordingly, this study aims to investigate the effects and possible mechanisms of ASP on the browning of WAT and mitophagy in vivo and in vitro. METHODS: In in vivo experiments, some mouse models were used including adipose tissue ASP-specific deficiency (ASP-/-), high fat diet (HFD)-induced obesity and white adipose browning; in in vitro experiments, some cell models were also established and used, including ASP-deficient 3T3-L1 preadipocyte (ASP-/-) and CL-316243 (CL, 1 µM)-induced browning. Based on these models, the browning of WAT and mitophagy were evaluated by morphology, functionality and molecular markers. RESULTS: Our in vivo data show that adipose tissue-specific deletion of ASP contributes to weight loss in mice; supplementation of ASP inhibits the expressions of browning-related proteins including UCP1, PRDM16 and PGC1ɑ during the cold exposure-induced browning, and promotes the expressions of mitophagy-related proteins including PINK1 and Parkin under the conditions of whether normal diet (ND) or HFD. Similarly, our in vitro data also show that the deletion of ASP in 3T3-L1 cells significantly increases the expressions of the browning-related proteins and decreases the expressions of the mitophagy-related proteins. CONCLUSIONS: These data demonstrate that ASP deletion can facilitate the browning and inhibit mitophagy in WAT. The findings will lay an experimental foundation for the development of new drugs targeting ASP and the clinical treatment of metabolic diseases related to obesity.

Single-crystalline van der Waals layered dielectric with high dielectric constant.

The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.

OsNAC3 regulates seed germination involving abscisic acid pathway and cell elongation in rice.

Seed germination is a critical trait for the success of direct seeding in rice cultivation. However, the underlying mechanism determining seed germination is largely unknown in rice. Here, we report that NAC transcription factor OsNAC3 positively regulates seed germination of rice. OsNAC3 regulates seed germination involving abscisic acid (ABA) pathway and cell elongation. OsNAC3 can directly bind to the promoter of ABA catabolic gene OsABA8ox1 and cell expansion gene OsEXP4, which consequently activates their expressions during seed germination. We also find that the expression of OsEXP4 is reduced by ABA during seed germination in rice. OsNAC3 regulates seed germination by influencing cell elongation of the embryo through directly affecting OsEXP4 expression and indirectly ABA-medicated OsEXP4 expression. The OsNAC3 elite haplotype is useful for genetic improvement of seed germination, and overexpression of OsNAC3 can significantly increase seed germination. We therefore propose that OsNAC3 is a potential target in breeding of rice varieties with high seed germination for direct seeding cultivation.

Resting cell formation in the marine diatom Thalassiosira pseudonana.

Resting cells represent a survival strategy employed by diatoms to endure prolonged periods of unfavourable conditions. In the oceans, many diatoms sink at the end of their blooming season and therefore need to endure cold and dark conditions in the deeper layers of the water column. How they survive these conditions is largely unknown. We conducted an integrative analysis encompassing methods from histology, physiology, biochemistry, and genetics to reveal the biological mechanism of resting-cell formation in the model diatom Thalassiosira pseudonana. Resting-cell formation was triggered by a decrease in light and temperature with subsequent catabolism of storage compounds. Resting cells were characterised by an acidic and viscous cytoplasm and altered morphology of the chloroplast ultrastructure. The formation of resting cells in T. pseudonana is an energy demanding process required for a biophysical alteration of the cytosol and chloroplasts to endure the unfavourable conditions of the deeper ocean as photosynthetic organisms. However, most resting cells (> 90%) germinate upon return to favorable growth conditions.

Targeting CD38/ ADP-ribosyl cyclase as a novel therapeutic strategy for identification of three potent agonists for leukopenia treatment.

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

Enzyme-Responsive Fluorescent Labeling Strategy for In Vivo Imaging of Gut Bacteria.

Myrosinase (Myr), as a unique ß-thioglucosidase enzyme capable of converting natural and gut bacterial metabolite glucosinolates into bioactive agents, has recently attracted a great deal of attention because of its essential functions in exerting homeostasis dynamics and promoting human health. Such nutraceutical and biomedical significance demands unique and reliable strategies for specific identification of Myr enzymes of gut bacterial origin in living systems, whereas the dearth of methods for bacterial Myr detection and visualization remains a challenging concern. Herein, we present a series of unique molecular probes for specific identification and imaging of Myr-expressing gut bacterial strains. Typically, an artificial glucosinolate with an azide group in aglycone was synthesized and sequentially linked with the probe moieties of versatile channels through simple click conjugation. Upon gut bacterial enzymatic cleavage, the as-prepared probe molecules could be converted into reactive isothiocyanate forms, which can further act as reactive electrophiles for the covalent labeling of gut bacteria, thus realizing their localized fluorescent imaging within a wide range of wavelength channels in live bacterial strains and animal models. Overall, our proposed method presents a novel technology for selective gut bacterial Myr enzyme labeling in vitro and in vivo. We envision that such a rational probe design would serve as a promising solution for chemoprevention assessment, microflora metabolic mechanistic study, and gut bacterium-mediated physiopathological exploration.

Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species.

Asprosin (ASP) is a newly-identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP-deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP-deficiency significantly alleviated the high-fat diet-induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator-activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP-deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF-κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl-CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.

Intracavity-loss controlled wavelength-tunable bidirectional mode-locked erbium-doped fiber laser.

Bidirectional wavelength-tunable mode-locked fiber lasers have demands for many applications. In our experiment, two frequency combs from a single bidirectional carbon nanotube mode-locked erbium-doped fiber laser are obtained. Continuous wavelength tuning is demonstrated in the bidirectional ultrafast erbium-doped fiber laser for the first time. We utilized the microfiber assisted differential loss-control effect on both directions to tune operation wavelength and it presents different wavelength tuning performances in two directions. Correspondingly, the repetition rate difference can be tuned from 98.6 Hz to 32 Hz by applying strain on microfiber within 23 µm stretching length. In addition, a minor repetition rate difference variation of 4.5 Hz is achieved. Such technique may provide possibility to expand wavelength range of dual-comb spectroscopy and broad its application fields.

Revealing the pulse dynamics in a Mamyshev oscillator: from seed signal to oscillator pulse.

The Mamyshev oscillator (MO) is a promising platform to generate high-peak-power pulse with environmentally stable operation. However, rare efforts have been dedicated to unveil the dynamics from seed signal to oscillator pulse, particularly for the multi-pulse operation. Herein, we investigate the buildup dynamics of the oscillator pulse from the seed signal in a fiber MO. It is revealed that the gain competition among the successively injected seed pulses leads to higher pump power that is required to ignite the MO, hence resulting in the higher optical gain that supports buildup of multiple oscillator pulses. The multiple oscillator pulses are identified to be evolved from the multiple seed pulses. Moreover, the dispersive Fourier transform (DFT) technique is used to reveals the real-time spectral dynamics during the starting process. As a proof-of-concept demonstration, a highly intensity-modulated pulse bunch was employed as the seed signal to reduce the gain competition effect and avoid the multi-pulse starting operation. The experimental results are verified by numerical simulations. These findings would give new insights into the pulse dynamics in MO, which will be meaningful to the communities interested in ultrafast laser technologies and nonlinear optics.

Observation of RIN reduction via spectral broadening in an NPR-based stretched pulse fiber laser.

We show that an optimum mode-locking state with low relative intensity noise (RIN) can be identified by continuous broadening of an optical spectrum in a stretched-pulse fiber laser based on nonlinear polarization rotation (NPR). Under the premise of keeping the overall spectral shape unchanged, either gradually increasing the pump power or unidirectionally adjusting the polarization controller (PC) can effectively reduce RIN as the optical spectral bandwidth broadens. The optimized intensity noise performance of the laser can be attributed to the increased pulse energy and reduced intra-cavity net dispersion. Moreover, the integrated RIN will further decrease as the maximum 3-dB bandwidth extends. In our experiment, the detected minimum integrated rms RIN is below 0.003% (from 100 Hz to 100 kHz). Our experimental results find that the absolute spectral width is not a necessary key condition for obtaining low RIN mode-locked laser, whereas it may help understand and design versatile low-noise ultrafast laser sources.

2B4 inhibits the apoptosis of natural killer cells through phosphorylated extracellular signal-related kinase/B-cell lymphoma 2 signal pathway.

BACKGROUND AIMS: Decades after the identification of natural killer (NK) cells as potential effector cells against malignantly transformed cells, an increasing amount of research suggests that NK cells are a prospective choice of immunocytes for cancer immunotherapy in addition to T lymphocytes for cancer immunotherapy. Recent studies have led to a breakthrough in the combination of hematopoietic stem-cell transplantation with allogeneic NK cells infusion for the treatment of malignant tumors. However, the short lifespan of NK cells in patients is the major impediment, limiting their efficacy. Therefore, prolonging the survival of NK cells will promote the application of NK-cell immunotherapy. As we have known, NK cells use a "missing-self" mechanism to lyse target cells and exert their functions through a wide array of activating, co-stimulatory and inhibitory receptors. Our previous study has suggested that CD244 (2B4), one of the co-stimulatory receptors, can improve the function of chimeric antigen receptor NK cells. However, the underlying mechanism of how 2B4 engages in the function of NK cells requires further investigation. Overall, we established a feeder cell with the expression of CD48, the ligand of 2B4, to investigate the function of 2B4-CD48 axis in NK cells, and meanwhile, to explore whether the newly generated feeder cell can improve the function of ex vivo-expanded NK cells. METHODS: First, K562 cells overexpressing 4-1BBL and membrane-bound IL-21 (mbIL-21) were constructed (K562-41BBL-mbIL-21) and were sorted to generate the single clone. These widely used feeder cells (K562-41BBL-mbIL-21) were named as Basic Feeder hereinafter. Based on the Basic feeder, CD48 was overexpressed and named as CD48 Feeder. Then, the genetically modified feeder cells were used to expand primary NK cells from peripheral blood or umbilical cord blood. In vitro experiments were performed to compare proliferation ability, cytotoxicity, survival and activation/inhibition phenotypes of NK cells stimulated via different feeder cells. K562 cells were injected into nude mice subcutaneously with tail vein injection of NK cells from different feeder system for the detection of NK in vivo persistence and function. RESULTS: Compared with Basic Feeders, CD48 Feeders can promote the proliferation of primary NK cells from peripheral blood and umbilical cord blood and reduce NK cell apoptosis by activating the p-ERK/BCL2 pathway both in vitro and in vivo without affecting overall phenotypes. Furthermore, NK cells expanded via CD48 Feeders showed stronger anti-tumor capability and infiltration ability into the tumor microenvironment. CONCLUSIONS: In this preclinical study, the engagement of the 2B4-CD48 axis can inhibit the apoptosis of NK cells through the p-ERK/BCL2 signal pathway, leading to an improvement in therapeutic efficiency.

Exfoliation of a Two-Dimensional Metal-Organic Framework for Enhanced Photocatalytic CO2 Reduction.

A two-dimensional metal-organic framework, FICN-12, was constructed from tris[4-(1H-pyrazole-4-yl)phenyl]amine (H3TPPA) ligands and Ni2 secondary building units. The triphenylamine moiety in the H3TPPA ligand readily absorbs UV-visible photons and sensitizes the Ni center to drive photocatalytic CO2 reduction. FICN-12 can be exfoliated into monolayer and few-layer nanosheets with a "top-down" approach, which exposes more catalytic sites and increases its catalytic activity. As a result, the nanosheets (FICN-12-MONs) showed photocatalytic CO and CH4 production rates of 121.15 and 12.17 µmol/g/h, respectively, nearly 1.4 times higher than those of bulk FICN-12.

The efficacy and safety of medication for treating overactive bladder in patients with Parkinson's disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials.

INTRODUCTION AND HYPOTHESIS: The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD). METHODS: Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis. RESULTS: We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy. CONCLUSIONS: Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

Genome-wide association study reveals candidate genes for pollution excreta traits in pigs.

Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.

Paeonol improves renal and vascular angiotensin II type 1 receptor function via inhibiting oxidative stress in spontaneously hypertensive rats.

BACKGROUND: Oxidative stress has been shown to play a critical role in the pathogenesis of hypertension. Paeonol, a major phenolic component extracted from Moutan Cortex, exerts a beneficial effect in preventing cardiovascular disease via reducing oxidative stress. The present study investigated the protective mechanism of paeonol against high blood pressure in spontaneous hypertension rats (SHRs). METHODS: Wistar-Kyoto (WKY) rats and SHRs received vehicle or peaonol in the drinking water for 5 weeks. Blood pressure was measured by tail-cuff plethysmography and oxidative stress in kidney and vascular tissue was examined by enzyme-linked immunosorbed assay. The functions of angiotensin II type 1 receptors (AT1R) in the kidney and mesenteric artery were measured by natriuresis and vasoconstrictor response, respectively. RESULTS: Compared with vehicle-treated WKY rats, vehicle-treated SHRs exhibited higher blood pressure, increased oxidative stress, accompanied by exaggerated diuretic and natriuretic responses to candesartan (AT1 receptor antagonist) and vasoconstrictor responses to angiotensin II (Ang II). Moreover, SHRs had higher ACE and AT1R in the kidney and mesenteric artery, and higher Ang II and lower renin levels. Interestingly, paeonol treatment reduced the candesartan-induced increase in diuresis and natriuresis and vasoconstrictor responses to Ang II, and lowered blood pressure in SHRs, accompanied by reducing AT1R protein expression in the kidney and mesenteric artery of SHR, and Ang II levels in plasma and increasing renin levels in renal cortex. In addition, these changes were associated with reducing oxidative stress. CONCLUSIONS: The present study suggests that paeonol improves renal and vascular AT1R functions by inhibition of oxidative stress, thus lowering blood pressure in SHRs.

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts.

Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. In recent years, the incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved. The platelets produced by MKs can treat thrombocytopenia-associated diseases in the body, and myeloid differentiation induced by MKs has the potential to improve myelosuppression and erythroleukemia. Currently, ethnomedicine is extensively used in the clinical treatment of blood diseases, and the recent literature has reported that many phytomedicines can improve the disease status through MK differentiation. This paper reviewed the effects of botanical drugs on megakaryocytic differentiation covering the period 1994-2022, and information was obtained from PubMed, Web of Science and Google Scholar. In conclusions, we summarized the role and molecular mechanism of many typical botanical drugs in promoting megakaryocyte differentiation in vivo, providing evidence as much as possible for botanical drugs treating thrombocytopenia and other related diseases in the future.

Averrhoa carambola L. fruit polyphenols ameliorate hyperlipidemia, hepatic steatosis, and hyperglycemia by modulating lipid and glucose metabolism in mice with obesity.

BACKGROUND: Hyperlipidemia, hepatic steatosis, and hyperglycemia are common metabolic complications of obesity. The objective of the present study is to investigate the in vivo protective effect of Averrhoa carambola L. fruit polyphenols (ACFP) on hyperlipidemia, hepatic steatosis, and hyperglycemia in mice with high-fat diet (HFD)-induced obesity and elucidate the mechanisms of action underlying the beneficial effects of ACFP. Thirty-six specific pathogen-free male C57BL/6J mice (4 weeks old, weighing 17.1-19.9 g) were randomly divided into three groups and fed with a low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with ACFP by intragastric administration for 14 weeks. Obesity-related biochemical indexes and hepatic gene expression levels were determined. The statistical analyses were conducted using one-way analysis of variance (ANOVA) followed by Duncan's multiple range test. RESULTS: The results showed that the body weight gain, serum triglycerides, total cholesterol, glucose, insulin resistance index, and steatosis grade in the ACFP group decreased by 29.57%, 26.25%, 27.4%, 19.6%, 40.32%, and 40%, respectively, compared to the HFD group. Gene expression analysis indicated that ACFP treatment improved the gene expression profiles involved in lipid and glucose metabolism compared to the HFD group. CONCLUSION: ACFP protected from HFD-induced obesity and obesity-associated hyperlipidemia, hepatic steatosis, and hyperglycemia by improving lipid and glucose metabolism in mice. © 2023 Society of Chemical Industry.

Influence of presurgical nasoalveolar molding (PNAM) treatment in maxillary dental arch width and nasolabial symmetry in patients with unilateral complete cleft lip and palate.

Unilateral complete cleft lip and palate (UCCLP) is one of the most severe clinical subphenotypes among nonsyndromic cleft lip and/or palate (NSCL/P), that complicates surgical repair operations. Presurgical nasoalveolar molding (PNAM) is a technique used to reshape the nose, lip and alveolar bone of infants with UCCLP before surgery (the modified Mohler rotation advancement cheiloplasty and two flap palatoplasty), with the potential to facilitate surgical repair. However, the effectiveness of PNAM treatment is still a matter of debate. In this paper, the 3Shape scanning system and 3dMD stereophotography were used to assess the short-term and long-term effects of PNAM treatment on the dental arch morphology and nasolabial features of patients with UCCLP, respectively. The findings indicated that PNAM treatment negatively affects both short-term and long-term dental arch shape compared to the treatment without PNAM, particularly in terms of limiting the transverse width of the maxillary canine-to-midline. Regarding the nasal and labial symmetry, PNAM improves the symmetry of the nasal alae in patients over 7 years old and the symmetry of the lip in patients under 7 years old. Moreover, UCCLP patients who received PNAM treatment exhibited a shorter and wider shape of the nostril on the cleft side compared to those without PNAM treatment. In clinical practice, the multidisciplinary team should carefully consider the advantages and disadvantages of the outcomes of PNAM treatment when treating infants with cleft lip and palate.