Optical Gain Spectrum and Confinement Factor of a Monolayer Semiconductor in an Ultrahigh-Quality Cavity.

Two-dimensional (2D) semiconductors have attracted great attention as a novel class of gain materials for low-threshold, on-chip coherent light sources. Despite several experimental reports on lasing, the underlying gain mechanism of 2D materials remains elusive due to a lack of key information, including modal gain and the confinement factor. Here, we demonstrate a novel approach to directly determine the absorption coefficient of monolayer WS2 by characterizing the whispering gallery modes in a van der Waals microdisk cavity. By exploiting the cavity's high intrinsic quality factor of 2.5 × 104, the absorption coefficient spectrum and confinement factor are experimentally resolved with unprecedented accuracy. The excitonic gain reduces the WS2 absorption coefficient by 2 × 104 cm-1 at room temperature, and the experimental confinement factor is found to agree with the theoretical prediction. These results are essential for unveiling the gain mechanism in emergent, low-threshold 2D-semiconductor-based laser devices.

Engineering acetylation platform for the total biosynthesis of D-amino acids.

Optically pure D-amino acids are key chemicals with various applications. Although the production of specific D-amino acids has been achieved by chemical synthesis or with in vitro enzyme catalysts, it is challenging to convert a simple carbon source into D-amino acids with high efficiency. Here, we design an artificial metabolic pathway by engineering bacteria to heterologously express racemase and N-acetyltransferase to produce N-acetyl-D-amino acids from L-amino acids. This new platform allows the cytotoxicity of D-amino acids to be avoided. The universal potential of this acetylation protection strategy for effectively synthesizing optically pure D-amino acids is demonstrated by testing sixteen amino acid targets. Furthermore, we combine pathway optimization and metabolic engineering in Escherichia coli and achieve practically useful efficiency with four specific examples, including N-acetyl-D-valine, N-acetyl-D-serine, N-acetyl-D-phenylalanine and N-acetyl-D-phenylglycine, with titers reaching 5.65 g/L, 5.25 g/L, 8.025 g/L and 130 mg/L, respectively. This work opens up opportunities for synthesizing D-amino acids directly from simple carbon sources, avoiding costly and unsustainable conventional approaches.

Dome-shaped mode lasing from liquid crystals for full-color lasers and high-sensitivity detection.

In this communication, we report a new class of oscillation mode, dome-shaped mode (DSM), in liquid crystal (LC) microlasers. A record high Q-factor over 24 000 is achieved in LC soft-matter microlasers. We successfully presented a proof-of-concept demonstration of red, green, blue (RGB) LC-DSM microlaser pixels with a 74% broader achievable color gamut than the standard RGB color space. Besides, the detection limit for acetone vapor molecules is as low as 0.5 ppm, confirming the excellent potential of the proposed LC-DSM microlaser in ultra-high sensitivity detection.

Strong Purcell effect in deep subwavelength coaxial cavity with GeSn active medium.

We propose a deep subwavelength plasmonic cavity based on a metal-coated coaxial structure with Ge0.9Sn0.1 as the active medium. A fundamental surface plasmon polariton mode is strongly confined on the sidewall of the metal core, with the quality factor up to 5×103 at 10 K. By reducing the cavity dimension to a few nanometers, this cavity mode shows a strong plasmon binding with the mode volume down to 8×10-10 (λ/n)3, and significant size-dependent damping caused by the non-local optical response. The Purcell factor is achieved as high as 2×109 at 10 K and 7×108 at 300 K. This cavity design provides a systematic guideline of scaling down the cavity size and enhancing the Purcell factor. Our theoretical demonstration and understanding of the subwavelength plasmonic cavity represent a significant step toward the large-scale integration of on-chip lasers with a low threshold.

Artificial Intelligence Can Effectively Predict Early Hematoma Expansion of Intracerebral Hemorrhage Analyzing Noncontrast Computed Tomography Image.

This study aims to develop and validate an artificial intelligence model based on deep learning to predict early hematoma enlargement (HE) in patients with intracerebral hemorrhage. A total of 1,899 noncontrast computed tomography (NCCT) images of cerebral hemorrhage patients were retrospectively analyzed to establish a predicting model and 1,117 to validate the model. And a total of 118 patients with intracerebral hemorrhage were selected based on inclusion and exclusion criteria so as to validate the value of the model for clinical prediction. The baseline noncontrast computed tomography images within 6 h of intracerebral hemorrhage onset and the second noncontrast computed tomography performed at 24 ± 3 h from the onset were used to evaluate the prediction of intracerebral hemorrhage growth. In validation dataset 1, the AUC was 0.778 (95% CI, 0.768-0.786), the sensitivity was 0.818 (95% CI, 0.790-0.843), and the specificity was 0.601 (95% CI, 0.565-0.632). In validation dataset 2, the AUC was 0.780 (95% CI, 0.761-0.798), the sensitivity was 0.732 (95% CI, 0.682-0.788), and the specificity was 0.709 (95% CI, 0.658-0.759). The sensitivity of intracerebral hemorrhage hematoma expansion as predicted by an artificial intelligence imaging system was 89.3%, with a specificity of 77.8%, a positive predictive value of 55.6%, a negative predictive value of 95.9%, and a Yoden index of 0.671, which were much higher than those based on the manually labeled noncontrast computed tomography signs. Compared with the existing prediction methods through computed tomographic angiography (CTA) image features and noncontrast computed tomography image features analysis, the artificial intelligence model has higher specificity and sensitivity in the prediction of early hematoma enlargement in patients with intracerebral hemorrhage.

Expert Consensus for Treating Cancer Patients During the Pandemic of SARS-CoV-2.

The sudden pandemic of SARS-Cov-2 (also known as novel coronavirus disease 2019, COVID-19) poses a severe threat to hundreds of millions of lives in the world. The complete cure of the virus largely relies on the immune system, which becomes particularly a challenge for the cancer subjects, whose immunity is generally compromised. However, in a constant evolving situation, the clinical data on the prevalence of SARS-Cov-2 for cancer patients is still limited. On top of a wide range of medical references and interim guidelines including CDC, NCI, ASCO, ESMO, NCCN, AACR, ESMO, and the National Health Commission of China, etc., we formed into a guideline based on our experience in our specialized cancer hospital in Wuhan, the originally endemic center of the virus. Furthermore, we formulated an expert consensus which was developed by all contributors from different disciplines after fully discussion based on our understanding and analysis of limited information of COVID-19. The consensus highlighted a multidisciplinary team diagnostic model with assessment of the balance between risks and benefits prior to treatment, individualizing satisfaction of patients' medical needs, and acceptability in ethics and patients' socio-economic conditions.

Sustainable Aromatic Aliphatic Polyesters and Polyurethanes Prepared from Vanillin-Derived Diols via Green Catalysis.

The design and preparation of polymers by using biobased chemicals is regarded as an important strategy towards a sustainable polymer chemistry. Herein, two aromatic diols, 4-(hydroxymethyl)-2-methoxyphenol and 2-(4-(hydroxymethyl)-2-methoxyphenoxy)ethanol, have been prepared in good yields through the direct reduction of vanillin and hydroxyethylated vanillin (4-(2-hydroxyethoxy)-3-methoxybenzaldehyde) using NaBH4, respectively. The diols were submitted to traditional polycondensation and polyaddition with acyl chlorides and diisocyanatos, and serials of new polyesters and polyurethanes were prepared in high yields with moderate molecular weight ranging from 17,000 to 40,000 g mol-1. Their structures were characterized by 1H NMR, 13C NMR and FTIR, and their thermal properties were studied by TGA and differential scanning calorimetry (DSC), indicating that the as-prepared polyesters and polyurethanes have Tg in the range of 16.2 to 81.2 °C and 11.6 to 80.4 °C, respectively.

Vanillin derived a carbonate dialdehyde and a carbonate diol: novel platform monomers for sustainable polymers synthesis.

Vanillin has been regarded as one of the important biomass-based platform chemicals for aromatic polymers synthesis. Herein, novel symmetric bis(4-formyl-2-methoxyphenyl)carbonate (BFMC) and bis(4-(hydroxymethyl)-2-methoxyphenyl)carbonate (BHMC) polymeric monomers have been synthesized in high yields using vanillin as a raw chemical, which have been submitted for polymer synthesis via well-established polymeric strategies. A new class of poly(carbonate ester)s oligomers with amide moieties in their side chain can be prepared by using the BFMC as one of monomers via the Passerini three compound reaction (3CR). A new class of poly(carbonate ester)s oligomers and poly(carbonate urethane)s can be prepared via reactions between BHMC with dicarboxylic acid chlorides and diisocyanates, respectively. Their structure have been confirmed by 1H NMR, 13C NMR and FTIR, and the gel permeation chromatograph (GPC) analysis shows that the Mn of poly(carbonate ester)s oligomers ranges from 3100 to 7900 with PDI between 1.31 and 1.65, and the Mn of poly(carbonate urethane)s ranges from 16 400 to 24 400 with PDI ranging from 1.36 to 2.17. The DSC analysis shows that the poly(carbonate ester)s oligomers have relative low T g ranging from 37.4 to 74.1 °C, and the poly(carbonate urethane)s have T g ranging from 97.3 to 138.3 °C, mainly correlating to the structure of dicarboxylic acid chlorides and diisocyanates used.

Molecular Beam Epitaxy of Highly Crystalline Monolayer Molybdenum Disulfide on Hexagonal Boron Nitride.

Atomically thin molybdenum disulfide (MoS2), a direct-band-gap semiconductor, is promising for applications in electronics and optoelectronics, but the scalable synthesis of highly crystalline film remains challenging. Here we report the successful epitaxial growth of a continuous, uniform, highly crystalline monolayer MoS2 film on hexagonal boron nitride (h-BN) by molecular beam epitaxy. Atomic force microscopy and electron microscopy studies reveal that MoS2 grown on h-BN primarily consists of two types of nucleation grains (0° aligned and 60° antialigned domains). By adopting a high growth temperature and ultralow precursor flux, the formation of 60° antialigned grains is largely suppressed. The resulting perfectly aligned grains merge seamlessly into a highly crystalline film. Large-scale monolayer MoS2 film can be grown on a 2 in. h-BN/sapphire wafer, for which surface morphology and Raman mapping confirm good spatial uniformity. Our study represents a significant step in the scalable synthesis of highly crystalline MoS2 films on atomically flat surfaces and paves the way to large-scale applications.

Chemical Vapor Deposition of High-Quality Large-Sized MoS2 Crystals on Silicon Dioxide Substrates.

Large-sized MoS2 crystals can be grown on SiO2/Si substrates via a two-stage chemical vapor deposition method. The maximum size of MoS2 crystals can be up to about 305 µm. The growth method can be used to grow other transition metal dichalcogenide crystals and lateral heterojunctions. The electron mobility of the MoS2 crystals can reach ≈30 cm2 V-1 s-1, which is comparable to those of exfoliated flakes.

Metformin Protects Cells from Mutant Huntingtin Toxicity Through Activation of AMPK and Modulation of Mitochondrial Dynamics.

Huntington's disease (HD) is a devastating neurodegenerative disease caused by the pathological elongation of the CAG repeats in the huntingtin gene. Caloric restriction (CR) has been the most reproducible environmental intervention to improve health and prolong life span. We have demonstrated that CR delayed onset and slowed disease progression in a mouse model of HD. Metformin, an antidiabetic drug, mimics CR by acting on cell metabolism at multiple levels. Long-term administration of metformin improved health and life span in mice. In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT. Further mechanistic study indicated that metformin activated AMP-activated protein kinase (AMPK) and that inhibition of AMPK activation reduced its protective effects on mutant HTT toxicity, suggesting that AMPK mediates the protection of metformin in HD cells. Furthermore, metformin treatment prevented mitochondrial membrane depolarization and excess fission and modulated the disturbed mitochondrial dynamics in HD cells. We confirmed that metformin crossed the blood-brain barrier after oral administration and activated AMPK in the mouse brain. Our results urge further evaluation of the clinical potential for use of metformin in HD treatment.

An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through modulation of the NF-κB signaling pathway.

The role of the adenosine A3 receptor (A3AR) in experimental colitis is controversial. The A3AR agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR-deficient mice suggest a pro-inflammatory role. However, there are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo. Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. Here we demonstrate a role for the NF-κB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-κB signaling pathway.

Activation of adenosine A3 receptor alleviates TNF-α-induced inflammation through inhibition of the NF-κB signaling pathway in human colonic epithelial cells.

To investigate the expression of adenosine A3 receptor (A3AR) in human colonic epithelial cells and the effects of A3AR activation on tumor necrosis factor alpha (TNF-α-) induced inflammation in order to determine its mechanism of action in human colonic epithelial cells, human colonic epithelial cells (HT-29 cells) were treated with different concentrations of 2-Cl-IB-MECA prior to TNF-α stimulation, followed by analysis of NF-κB signaling pathway activation and downstream IL-8 and IL-1ß production. A3AR mRNA and protein were expressed in HT-29 cells and not altered by changes in TNF-α or 2-Cl-IB-MECA. Pretreatment with 2-Cl-IB-MECA prior to stimulation with TNF-α attenuated NF-κB p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of IκB-α, and reduced phosphorylated-IκB-α level significantly, compared to TNF-α-only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF-α-stimulated IL-8 and IL-1ß mRNA expression and secretion, compared to the TNF-α-only treated group. These results confirm that A3AR is expressed in human colonic epithelial cells and demonstrate that its activation has an anti-inflammatory effect, through the inhibition of NF-κB signaling pathway, which leads to inhibition of downstream IL-8 and IL-1ß expression. Therefore, A3AR activation may be a potential treatment for gut inflammatory diseases such as inflammatory bowel disease.

Effects of delivering recombinant tissue plasminogen activator on a new infusion system during endovascular intervention in patients with lower limb ischemia.

BACKGROUND: To evaluate the feasibility and effects of recombinant tissue plasminogen activator (rt-PA) delivered by a new infusion system during endovascular intervention therapy in patients who had limb ischemia within 6 months. METHODS: From November 2006 to December 2010, 103 consecutive patients were randomly distributed in two groups. 10 mg (group A) and 5 mg (group B) bolus of rt-PA was respectively injected into the proximal occlusive lesion by a new infusion system. Subsequently, additional rt-PA of 10 mg (group A) and 5 mg (group B) was injected into the thrombotic occlusion, respectively. Significant underlying lesions were treated by endovascular intervention or surgery. Rates of major and minor complication, procedural success, and clinical success were evaluated statistically. RESULTS: Rates of complete lysis and partial lysis success were 12.6% (13 of 103) and 87.4% (90 of 103), respectively. To treat underlying lesions, 84.5% (84 of 103) patients received balloon angioplasty/stent implantation and 4.9% (5 of 103) patients received surgical correction. After final definitive treatment, procedural success rate was up to 99% (102 of 103) and clinical success rate was 100%. Comorbidity conditions and patient characteristics did not statistically influence the rates of success and complication. During the follow-up period of 30-day, 6-, 12- month, there was no statistical difference in the amputation-free survival rates between these two groups. CONCLUSION: It is safe and effective to treat lower limb ischemia by combining adjunctive endovascular intervention with bolus of rt-PA (10 to 20 mg) given by a new infusion system. But long-term effects of thrombolysoangioplasty therapy in treating lower limb ischemia must be confirmed by large-scale population studies before routine use.

Gastrointestinal bleeding after intracerebral hemorrhage: a retrospective review of 808 cases.

BACKGROUND: This study examined the incidence and risk factors for gastrointestinal (GI) bleeding after spontaneous intracerebral hemorrhage (ICH). METHODS: The available medical records of patients with ICH admitted from June 2008 to December 2009 for any episode of GI bleeding, possible precipitating factors and administration of ulcer prophylaxis were reviewed. RESULTS: The prevalence of GI bleeding was 26.7%, including 3 cases of severe GI bleeding (0.35%). Patients with GI bleeding had significantly longer hospital stay and higher in-hospital mortality compared with patients without GI bleeding. Multivariate logistic regression analyses showed that age, Glasgow Coma Scale scores, sepsis and ICH volume were independent predictors of GI bleeding. About 63.4% of patients with ICH received stress ulcer prophylaxis. CONCLUSIONS: GI bleeding occurred frequently after ICH, but severe events were rare. Age, Glasgow Coma Scale score, sepsis and ICH volume were independent predictors of GI bleeding occurring after ICH.

Clinical pharmacology considerations in biologics development.

Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram.

Impact of disrupting adenosine A3 receptors (A3⁻/⁻ AR) on colonic motility or progression of colitis in the mouse.

BACKGROUND: Pharmacological studies suggest that adenosine A3AR influences motility and colitis. Functional A3⁻/⁻AR knockout mice were used to prove whether A3AR activation is involved in modulating either motility or colitis. METHODS: A3AR was probed by polymerase chain reaction (PCR) genotyping, Western blot, and immunochemistry. Motility was assessed in vivo by artificial bead-expulsion, stool-frequency, and FITC-dextran transit. Colitis was induced with dextran sodium sulfate (DSS) in A3⁻/⁻AR or wildtype (WT) age- and sex-matched controls. Progression of colitis was evaluated by histopathology, changes in myeloperoxidase (MPO), colon length, CD4(+) -cells, weight-loss, diarrhea, and the guaiac test. RESULTS: Goat anti-hu-A3 antiserum identified a 66 kDa immunogenic band in colon. A3AR-immunoreactivity is expressed in SYN(+) -nerve varicosities, s-100(+) -glia, and crypt cells, but not 5-HT(+) (EC), CD4(+) (T), tryptase(+) (MC), or muscle cells. A3AR immunoreactivity in myenteric ganglia of distal colon >> proximal colon by a ratio of 2:1. Intestinal transit and bead expulsion were accelerated in A3⁻/⁻AR mice compared to WT; stool retention was lower by 40%-60% and stool frequency by 67%. DSS downregulated A3AR in epithelia. DSS histopathology scores indicated less mucosal damage in AA3⁻/⁻AR mice than WT. A3⁻/⁻AR phenotype protected against DSS-induced weight loss, neutrophil (MPO), or CD4(+) -T cell infiltration, colon shortening, change in splenic weight, diarrhea, or occult-fecal blood. CONCLUSIONS: Functional disruption of A3AR in A3⁻/⁻AR mice alters intestinal motility. We postulate that ongoing release of adenosine and activation of presynaptic-inhibitory A3AR can slow down transit and inhibit the defecation reflex. A3AR may be involved in gliotransmission. In separate studies, A3⁻/⁻AR protects against DSS colitis, consistent with a novel hypothesis that A3AR activation contributes to development of colitis.

Activation of adenosine low-affinity A3 receptors inhibits the enteric short interplexus neural circuit triggered by histamine.

We tested the novel hypothesis that endogenous adenosine (eADO) activates low-affinity A3 receptors in a model of neurogenic diarrhea in the guinea pig colon. Dimaprit activation of H2 receptors was used to trigger a cyclic coordinated response of contraction and Cl(-) secretion. Contraction-relaxation was monitored by sonomicrometry (via intracrystal distance) simultaneously with short-circuit current (I(sc), Cl(-) secretion). The short interplexus reflex coordinated response was attenuated or abolished by antagonists at H2 (cimetidine), 5-hydroxytryptamine 4 receptor (RS39604), neurokinin-1 receptor (GR82334), or nicotinic (mecamylamine) receptors. The A1 agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) abolished coordinated responses, and A1 antagonists could restore normal responses. A1-selective antagonists alone [8-cyclopentyltheophylline (CPT), 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX), or 8-cyclopentyl-N(3)-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-xanthine (FSCPX)] caused a concentration-dependent augmentation of crypt cell secretion or contraction and acted at nanomolar concentrations. The A3 agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) abolished coordinated responses and the A3 antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) could restore and further augment responses. The IB-MECA effect was resistant to knockdown of adenosine A1 receptor with the irreversible antagonist FSCPX; the IC(50) for IB-MECA was 0.8 microM. MRS1191 alone could augment or unmask coordinated responses to dimaprit, and IB-MECA suppressed them. MRS1191 augmented distension-evoked reflex I(sc) responses. Adenosine deaminase mimicked actions of adenosine receptor antagonists. A3 receptor immunoreactivity was differentially expressed in enteric neurons of different parts of colon. After tetrodotoxin, IB-MECA caused circular muscle relaxation. The data support the novel concept that eADO acts at low-affinity A3 receptors in addition to high-affinity A1 receptors to suppress coordinated responses triggered by immune-histamine H2 receptor activation. The short interplexus circuit activated by histamine involves adenosine, acetylcholine, substance P, and serotonin. We postulate that A3 receptor modulation may occur in gut inflammatory diseases or allergic responses involving mast cell and histamine release.

Gynura root induces hepatic veno-occlusive disease: a case report and review of the literature.

Gynura root has been used extensively in Chinese folk medicine and plays a role in promoting microcirculation and relieving pain. However, its hepatic toxicity should not be neglected. Recently, we admitted a 62-year old female who developed hepatic veno-occlusive disease (HVOD) after ingestion of Gynura root. Only a few articles on HVOD induced by Gynura root have been reported in the literature. It is suspected that pyrrolizidine alkaloids in Gynura root might be responsible for HVOD. In this paper, we report a case of HVOD and review the literature.