Highly Efficient Fabrication of Biomimetic Nanoscaled Tendrils for High-Performance PM0.3 Air Filters.

Particulate matter pollution has become a serious public health issue, especially with the outbreak of new infectious diseases. However, most existing air filtration materials face challenges such as being too bulky, having high resistance, and a trade-off between filtration efficiency and air permeability. Here, a unique electro-blown spinning technique is used to prepare an air filter made of biomimetic nanoscaled tendril nonwovens (Nano-TN). The introduction of an airflow field significantly increases the whipping frequency and the strain mismatch of composite jets, achieving large-scale and highly efficient preparation of Nano-TN. The resultant Nano-TN has an ultrahigh porosity (97%) and a small pore size (2.9 µm). At the same filtration level, its air resistance is 37% lower than that of traditional straight nanofibrous nonwovens and has a higher dust-holding capacity. Moreover, compared with traditional three-dimensional air filters, the Nano-TN filter is thinner, offering tremendous application prospects in various environmental purification and personal protection fields.

Late-Stage Saturation of Drug Molecules.

The available methods of chemical synthesis have arguably contributed to the prevalence of aromatic rings, such as benzene, toluene, xylene, or pyridine, in modern pharmaceuticals. Many such sp2-carbon-rich fragments are now easy to synthesize using high-quality cross-coupling reactions that click together an ever-expanding menu of commercially available building blocks, but the products are flat and lipophilic, decreasing their odds of becoming marketed drugs. Converting flat aromatic molecules into saturated analogues with a higher fraction of sp3 carbons could improve their medicinal properties and facilitate the invention of safe, efficacious, metabolically stable, and soluble medicines. In this study, we show that aromatic and heteroaromatic drugs can be readily saturated under exceptionally mild rhodium-catalyzed hydrogenation, acid-mediated reduction, or photocatalyzed-hydrogenation conditions, converting sp2 carbon atoms into sp3 carbon atoms and leading to saturated molecules with improved medicinal properties. These methods are productive in diverse pockets of chemical space, producing complex saturated pharmaceuticals bearing a variety of functional groups and three-dimensional architectures. The rhodium-catalyzed method tolerates traces of dimethyl sulfoxide (DMSO) or water, meaning that pharmaceutical compound collections, which are typically stored in wet DMSO, can finally be reformatted for use as substrates for chemical synthesis. This latter application is demonstrated through the late-stage saturation (LSS) of 768 complex and densely functionalized small-molecule drugs.

Slit-Robo signalling establishes a Sphingosine-1-phosphate gradient to polarise fin mesenchyme.

Immigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical domain of the fin, orientate limb mesenchyme cell polarity, migration, division and adhesion. The zebrafish mutant stomp displays defects in fin morphogenesis including blister formation and associated loss of orientation and adhesion of immigrating fin mesenchyme cells. Positional cloning of stomp identifies a mutation in the gene encoding the axon guidance ligand, Slit3. We provide evidence that Slit ligands derived from immigrating mesenchyme act via Robo receptors at the apical ectodermal ridge (AER) to promote release of sphingosine-1-phosphate (S1P). S1P subsequently diffuses back to the mesenchyme to promote their polarisation, orientation, positioning and adhesion to the interstitial matrix of the fin fold. We thus demonstrate the coordination of the Slit-Robo and S1P signalling pathways in fin fold morphogenesis. Our work introduces a mechanism regulating the orientation, positioning and adhesion of its constituent cells.

Intermolecular donor-acceptor stacking to suppress triplet exciton diffusion for long-persistent organic room-temperature phosphorescence.

Controlling triplet states is crucial to improve the efficiency and lifetime of organic room temperature phosphorescence (ORTP). Although the intrinsic factors from intramolecular radiative and non-radiative decay have been intensively investigated, the extrinsic factors that affect triplet exciton quenching are rarely reported. Diffusion to the defect sites inside the crystal or at the crystal surface may bring about quenching of triplet exciton. Here, the phosphorescence lifetime is found to have a negative correlation with the triplet exciton diffusion coefficient based on the density functional theory (DFT)/time-dependent density functional theory (TD-DFT) calculations on a series of ORTP materials. For systems with a weak charge transfer (CT) characteristic, close π-π stacking will lead to strong triplet coupling and fast triplet exciton diffusion in most cases, which is detrimental to the phosphorescence lifetime. Notably, for intramolcular donor-acceptor (D-A) type systems with a CT characteristic, intermolecular D-A stacking results in ultra-small triplet coupling, thus contributing to slow triplet diffusion and long phosphorescence lifetime. These findings shed some light on molecular design toward high-efficiency long persistent ORTP.

Tracing the Flu Symptom Progression via a Smart Face Mask.

Respiration and body temperature are largely influenced by the highly contagious influenza virus, which poses persistent global public health challenges. Here, we present a wireless all-in-one sensory face mask (WISE mask) made of ultrasensitive fibrous temperature sensors. The WISE mask shows exceptional thermosensitivity, excellent breathability, and wearing comfort. It offers highly sensitive body temperature monitoring and respiratory detection capabilities. Capitalizing on the advances in the Internet of Things and artificial intelligence, the WISE mask is further demonstrated by customized flexible circuitry, deep learning algorithms, and a user-friendly interface to continuously recognize the abnormalities of both the respiration and body temperature. The WISE mask represents a compelling approach to tracing flu symptom progression in a cost-effective and convenient manner, serving as a powerful solution for personalized health monitoring and point-of-care systems in the face of ongoing influenza-related public health concerns.

Recent Advances in Dearomative Partial Reduction of Benzenoid Arenes.

Dearomative partial reduction is an extraordinary approach for transforming benzenoid arenes and has been well-known for many decades, as exemplified by the dehydrogenation of Birch reduction and the hydroarylation of Crich addition. Despite its remarkable importance in synthesis, this field has experienced slow progress over the last half-century. However, a revival has been observed with the recent introduction of electrochemical and photochemical methods. In this Minireview, we summarize the recent advancements in dearomative partial reduction of benzenoid arenes, including dihydrogenation, hydroalkylation, arylation, alkenylation, amination, borylation and others. Further, the intriguing utilization of dearomative partial reduction in the synthesis of natural products is also emphasized. It is anticipated that this Minireview will stimulate further progress in arene dearomative transformations.

FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis.

In brief: The appropriate growth and functions of Sertoli cells are crucial to testis development and spermatogenesis in mammals. This study reveals a novel mechanism of follicle-stimulating hormone in immature porcine Sertoli cell proliferation. Abstract: Follicle-stimulating hormone (FSH) is a major Sertoli cell mitogen that binds to the FSH receptor. Sertoli cells are indispensable for testis development and spermatogenesis. However, the regulatory mechanisms of FSH in immature Sertoli cell proliferation have not been determined, particularly in domestic animals. In the present study, we identified the regulatory mechanisms of FSH during immature porcine Sertoli cell proliferation. Transcriptome analysis revealed 114 differentially expressed genes that were induced by FSH treatment, which contains 68 upregulated and 46 downregulated genes. These differentially expressed genes were enriched in multiple pathways, including the Ras signaling pathway. Knockdown of the CC-chemokine receptor 7 (CCR7) gene, which was upregulated by FSH, inhibited cell cycle progression by arresting cells in the G1 phase and reduced the cell proliferation and ERK1/2 phosphorylation. In addition, Kobe0065 inhibited Ras signaling in a similar manner as CCR7 knockdown. Furthermore, FSH abolished the effects of Ras signaling pathway inhibition and CCR7 knockdown. Collectively, FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis. Our results provide novel insights into the regulatory mechanism of FSH in porcine testis development and spermatogenesis by deciding the fate of immature porcine Sertoli cells.

Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer.

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation and Birch reduction are the two broadly utilized approaches for (hetero)arene reduction across academia and industry over the last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline and isoquinoline reduction protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom transfer (HAT). The design of this protocol bypasses the conventional metric of reduction reaction, that is, the reductive potential, and instead relies on the triplet energies of the chemical moieties and the kinetic barriers of energy and hydrogen atom transfer events. Many reducing labile functional groups, which were incompatible with previous (hetero)arene reduction reactions, are retained in this reaction. We anticipate that this protocol will trigger the further advancement of chemoselective arene reduction and enable the current arene-rich drug space to escape from flatland.

Visible-Light Photocatalyzed peri-(3 + 2) Cycloadditions of Quinolines.

Cycloaddition reactions─epitomized by the Diels-Alder reaction─offer an arguably unmatched springboard for achieving chemical complexity, often with excellent selectivity, in a modular single step. We report the synthesis of aza-acenaphthenes in a single step by an unprecedented formal peri-(3 + 2) cycloaddition of simple quinolines with alkynes. A commercially available iridium complex exerts a dual role of photosensitizer and photoredox catalyst, fostering a cyclization/rearomatization cascade. The initial energy-transfer phase leads to the acenaphthene skeleton, while the ensuing redox shuttling step leads to aromatization. We applied this technology to 8-substituted quinolines and phenanthrolines, which smoothly reacted with both terminal and internal alkynes with excellent levels of regio- and diastereoselectivity. Density functional theory calculations revealed the intertwined EnT/SET nature of the process and offered guiding design principles for the synthesis of new aza-acenaphthenes.

Photochemical Dearomative Cycloadditions of Quinolines and Alkenes: Scope and Mechanism Studies.

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically congested products and reaction of highly substituted alkenes and allenes. In addition, the mechanistic details of the process are studied, which revealed a reversible radical addition and a selectivity-determining radical recombination. The regio- and stereochemical outcome of the reaction is also rationalized.

Activated Galectin-9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia.

Tim-3 is a negative immunoregulator in anti-tumor response, but its mechanism in chronic lymphocytic leukemia (CLL) is not yet clear. The aim of this study was to understand the role of Galectin-9/Tim-3 signaling pathway in the regulation of CD4+ T cell subsets in CLL patients. Flow cytometry results showed that the number of Treg cells obviously increased, and there was a significant Treg/Th17 imbalance in CLL patients. In addition, Tim-3 overexpressed on the surface of Th1 and Treg cells in CLL patients. The levels of Galectin-9 and IL-10 were significantly elevated in patients of CLL, especially in stages of Binet B, and C. However, IFN-γ decreased. Moreover, Galectin-9 in CLL patients was positively correlated with the number of Tim-3+ Treg cells and the level of IL-10. Interestingly, when the Tim-3/Galectin-9 pathway was blocked in vitro, the level of IL-10 in the culture supernatant of CD4+ T was significantly reduced, while the levels of IFN-γ and TNF-α were increased. After co-culture with activated Th1 cells, the apoptosis of CLL cells was significantly increased, and this effect was reversed after treatment with Tim-3+ Tregs. In summary, Galectin-9/Tim-3 are elevated in CLL and associated with disease progression. By the negative regulation of CD4+ T cells, activated Galectin-9/Tim-3 suppresses Th1 effector function and also promotes Treg to be involved in immune escape of CLL. This pathway might become the potential target of immunotherapy in CLL patients.

Effects of Sevoflurane-Propofol-Balanced Anesthesia on Flash Visual Evoked Potential Monitoring in Spine Surgery: A Randomized Noninferiority Trial.

BACKGROUND: Intraoperative flash visual evoked potential (FVEP) can be used to monitor visual function during spine surgery. However, it is limited due to the previous perception of its sensitivity to inhalation anesthesia. We conducted this trial to test the noninferiority of sevoflurane-propofol-balanced anesthesia (BA) versus popular propofol-based total intravenous anesthesia (TIVA) on the amplitude of FVEP during spine surgery. METHODS: A total of 60 patients undergoing spine surgery were randomized to receive either sevoflurane-propofol-balanced anesthesia (BA group) or propofol-based total intravenous anesthesia (TIVA group) for anesthesia maintenance. We titrated the propofol plasma concentration to keep the bispectral index (BIS) values between 40 and 50. The primary outcome was the P100-N145 amplitudes of FVEP at 120 minutes after induction of anesthesia. The noninferiority margin (δ) was defined as 10% of the P100-N145 amplitude at 120 minutes after induction in the TIVA group. If the confidence interval (CI) for mean differences of P100-N145 amplitude at 120 minutes after induction between BA and TIVA groups lied above the lower limit of -δ with P < .025, we defined BA group was noninferior to TIVA group. RESULTS: Fifty-nine patients were included in the final analysis. The amplitude of P100-N145 at 120 minutes after anesthesia induction in group BA was noninferior to group TIVA (3.8 [1.3] µV vs 3.2 [1.6] µV, -δ = -0.32, mean difference, 0.57, 95% CI, -0.18 to 1.33, P for noninferiority = .015). CONCLUSIONS: The effect of 0.5 minimum alveolar concentration (MAC) of sevoflurane-propofol-balanced anesthesia on the P100-N145 amplitude of FVEP was noninferior to that of propofol-based TIVA under comparable BIS range.

EIF5A2 Is Involved in the Biological Process of Cervical Cancer Cells through AGR2.

INTRODUCTION: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer. METHODS: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined. RESULTS: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells. CONCLUSION: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.

miR-140-3p impedes the proliferation of human cervical cancer cells by targeting RRM2 to induce cell-cycle arrest and early apoptosis.

Cervical cancer is a critically malignant tumor with the second mortality of females worldwide. MicroRNAs (miRNAs) are short but regulatory non-coding RNAs playing a pivotal role in many biological processes including tumorigenesis. However, the exact role of miR-140-3p in cervical cancer remains to be elucidated. Here we identified that miR-140-3p was significantly reduced in cervical cancer tissues by comprehensive analysis of TCGA data, hinting that higher expression level of miR-140-3p predicted a good clinical prognosis. Quantitative real-time PCR (RT-qPCR) assay was performed to confirm the negative correlation between miR-140-3p expression level and human cervical cancer tissues as well as various cervical cancer cell lines. To clarify the certain role of miR-140-3p, forced expression by microRNA mimics was applied in Caski and C33A cells, showing that miR-140-3p overexpression significantly impeded the proliferation of cervical cancer cells by cell count kit (CCK-8) assay. Western blot analysis of cell cycle-related proteins Cyclin A, Cyclin B1 and Cyclin D1 have further confirmed the cell cycle arrest was induced by the ectopic expression of miR-140-3p. Annexin-V based FACS analysis also found the simultaneous appearance of early apoptotic cell population in miR-140-3p overexpression cells. The protein level of BCL-2 was attenuated in accompany with elevated Bax and Cleaved caspase-3 protein, indicating miR-140-3p overexpression induced early apoptosis. Mechanistically, we demonstrated that miR-140-3p could target the 3'UTR of RRM2 which has been proved to be highly involved in the onset of cancer. Furthermore, upregulation of miR-140-3p and RRM2 failed to inhibit the proliferation of human cervical cancer cells, revealing that RRM2 served as the target downstream gene of miR-140-3p abolishing its ability as a tumor suppressor. Overall, we figured out the new role of miR-140-3p in cervical cancer and concluded that miR-140-3p was a candidate of cancer control in preclinical.

Gadolinium Photocatalysis: Dearomative [2+2] Cycloaddition/Ring-Expansion Sequence with Indoles.

Lanthanide photocatalysts are much less investigated in synthetic chemistry than rare and expensive late transition metals. We herein introduce GdIII photocatalysis of a highly regioselective, intermolecular [2+2] photocycloaddition/ring-expansion sequence with indoles, which could provide divergent access to cyclopenta[b]indoles and indolines. A simple and commercially available Gd(OTf)3 salt is sufficient for this visible-violet-light-induced transformation. The reaction proceeds either through a transient or start-to-end dearomatization cascade and shows excellent regioselectivity (usually >95:5 r.r.), broad scope (59 examples), good functional group tolerance and facile scale-up under mild, direct visible-light-excitation conditions. Mechanistic investigations reveal that direct excitation of the Gd(OTf)3 /indole mixture gives an excited state intermediate, which undergoes the subsequent [2+2] cycloaddition and cyclobutane-expansion cascade.

Total laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma under a single surgical position.

BACKGROUND: To assess the feasibility and effectiveness of total laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma (UUTUC) under a single surgical position. METHODS: The medical data of 89 UUTUC patients were collected, who were treated in our institution from Jan 2016 to Jun 2018. The 45 cases that underwent total laparoscopic nephroureterectomy with a single position were allocated in the test group, while the 44 patients who received retroperitoneal laparoscopy combined with hypogastric oblique incision were assigned in the control group. We compared the two groups in perioperative indicators and tumor recurrence rate and analyzed the clinical effect of the new surgical treatment of UUTUC. RESULTS: All 89 operations for UUTUC were successful and had no conversion to open surgery. No obvious complications occurred during the perioperative period. The test group had significantly shorter average operation time (96.58 ± 8.56 min versus 147.45 ± 9.16 min), less blood loss (39.58 ± 4.15 ml versus 46.50 ± 4.58 ml), earlier ambulation (7.47 ± 1.01 h versus 11.39 ± 1.82 h), and shorter length of stay in hospital (6.98 ± 1.14 days versus 9.89 ± 1.51 days) (P < 0.05). The visual analogue scale (VAS) scores of the test group at 1 h, 12 h, and 24 h after operation were lower compared with those of the control group (P < 0.05). No significant difference was found in the tumor stage, tumor grade, postoperative gastrointestinal function recovery time, follow-up time, and tumor recurrence rate between the two groups. CONCLUSIONS: Compared with the traditional surgical methods, the total laparoscopic treatment of UUTUC under a single surgical position had advantages of shorter operation time, less blood loss, and early postoperative ambulation. The new operative method could shorten the length of stay and accelerate recovery of patients, and it is a viable surgical procedure which deserved clinical application and promotion. TRIAL REGISTRATION: Our trial was approved and has been registered in the ethics committee of the Yantai Yuhuangding Hospital (Approval NO.[2015]171) .

Visible-Light-Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions.

Despite significant progress in aliphatic decarboxylation, an efficient and general protocol for radical aromatic decarboxylation has lagged far behind. Herein, we describe a general strategy for rapid access to both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters followed by their successive use in divergent carbon-heteroatom and carbon-carbon bond-forming reactions. Identification of a suitable activator for carboxylic acids is the key to bypass a competing single-electron-transfer mechanism and "switch on" an energy-transfer-mediated homolysis of unsymmetrical σ-bonds for a concerted fragmentation/decarboxylation process.

Catalytic Asymmetric Synthesis of Fluoroalkyl-Containing Compounds by Three-Component Photoredox Chemistry.

Multicomponent reactions allow the construction of molecular complexity in an economical fashion, fluorinated compounds play an important role in pharmaceuticals and agrochemicals, whereas visible light is an abundant and sustainable source of energy for activating chemical transformations. Here we report a visible-light-induced asymmetric three-component fluoroalkylation reaction scheme catalyzed by a chiral-at-rhodium Lewis acid. The photoredox process is mediated by the inexpensive, commercially available organic photoredox mediator 4,4'-difluorobenzil, which upon activation by visible light induces the generation of perfluoroalkyl radicals from their sulfinates via single electron transfer oxidation. The fluorinated radicals are trapped by electron-rich C-C double bonds to deliver α-oxy carbon-centered radicals, followed by a subsequent stereocontrolled reaction with acceptor-substituted alkenes. This three-component fluoroalkylation scheme provides a range of complex fluoroalkyl-containing chiral compounds under dual C-C bond formation with high enantioselectivities (up to 98 % ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives are observed. Broad substrate scope (25 examples), excellent functional group tolerance, scalability of the reaction, along with the option to recover the chiral catalyst and photoredox mediator reveal the practicability of this methodology in organic synthesis for the rapid synthesis of fluorinated chiral molecules.

Synthesis of ß-Substituted γ-Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis.

ß-Substituted chiral γ-aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of ß-substituted γ-aminobutyric acid derivatives through visible-light-induced photocatalyst-free asymmetric radical conjugate additions is reported. Various ß-substituted γ-aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42-89 %) and with excellent enantioselectivity (90-97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram, and (S)-nebracetam.

Visible-Light-Activated Asymmetric ß-C-H Functionalization of Acceptor-Substituted Ketones with 1,2-Dicarbonyl Compounds.

We report a visible-light-activated asymmetric ß-C(sp3)-H functionalization of 2-acyl imidazoles and 2-acylpyridines with 1,2-dicarbonyl compounds (typically α-ketoesters) catalyzed by a tailored stereogenic-at-rhodium Lewis acid catalyst. The C-C bond formation products are obtained in high yields (up to 99%) and with excellent stereoselectivities (up to >20:1 dr and up to >99% ee). Experimental and computational studies support a mechanism in which a photoactivated Rh-enolate transfers a single electron to the 1,2-dicarbonyl compound followed by proton transfer and a subsequent stereocontrolled radical-radical recombination.