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Transparency order (TO{\mathcal{TO}}) is one of the indicators used to measure the resistance of (n,m)\left(n,m)-function to differential power analysis. At present, there are three definitions: TO{\mathcal{TO}}, redefined transparency order (ℛTO{\mathcal{ {\mathcal R} TO}}), and modified transparency order (ℳTO{\mathcal{ {\mathcal M} TO}}). For the first time, we give one necessary and sufficient condition for (n,m)\left(n,m)-function reaching TO=m{\mathcal{TO}}=m and completely characterize (n,m)\left(n,m)-functions reaching TO=m{\mathcal{TO}}=m for any nn and mm. We find that any (n,1)\left(n,1)-function cannot reach TO=m{\mathcal{TO}}=m for odd nn. Based on the matrix product, the necessary conditions for (n,m)\left(n,m)-function reaching ℳTO=m{\mathcal{ {\mathcal M} TO}}=m or ℛTO=m{\mathcal{ {\mathcal R} TO}}=m are given, respectively. Finally, it is proved that any balanced (n,m)\left(n,m)-function cannot reach the upper bound on TO{\mathcal{TO}} (or ℛTO{\mathcal{ {\mathcal R} TO}}, ℳTO{\mathcal{ {\mathcal M} TO}}).

It is economically desirable to develop a material that can simultaneously detect and recover uranium. Herein, a CC-bridged two-dimensional metal-covalent organic framework (Cu-BTAN-AO MCOF) was constructed by condensation of metal single crystals with a rigid structure (Cu3(PyCA)3) and cyano monomers (BTAN) via Knoevenagel reaction for simultaneous detection and adsorption of uranium. The amidoxime group within the pore and the presence of unsaturated Cu(I) in the framework facilitate the adsorption of uranyl ions onto the amidoxime group, leading to fluorescence quenching via the photoinduced electron transfer (PET) mechanism, achieving a detection limit of as low as 167 nM uranyl ions. Furthermore, Cu-BTAN-AO demonstrates exceptional efficiency in capturing uranium from wastewater characterized by rapid kinetics and superior selectivity. It is noteworthy that Cu-BTAN-AO is the first example of simultaneous detection, adsorption and chemical reduction of uranium using metal centers and functional groups in MCOF, indicating that Cu-BTAN-AO has great potential for the detection and recovery of uranium-containing wastewater. This design strategy may also be applicable to advancing sensing and energy materials for other important metal ions.

Abstract In this study, the blank hydrogels and the niosomal hydrogels loading coenzyme Q10 (CoQ10) were prepared by carbomer (CBM) and scleroglucan (SCL), and their physicochemical properties were characterized in [...]

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Abstract The type of reactions and the availability of monomers for the synthesis of sp 2 -c linked covalent organic frameworks (COFs) are considerably limited by the irreversibility of the C=C bond. Herein, inspired by the Claisen-Schmidt condensation reaction, two propenone-linked (C=C–C=O) COFs (named Py-DAB and PyN-DAB) are developed based on the base-catalyzed nucleophilic addition reaction of ketone-activated α-H with aromatic aldehydes. The introduction of propenone structure endows COFs with high crystallinity, excellent physicochemical stability, and intriguing optoelectronic properties. Benefitting from the rational design on the COFs skeleton, Py-DAB and PyN-DAB are applied to the extraction of radionuclide uranium. In particular, PyN-DAB shows excellent removal rates (>98%) in four uranium mine wastewater samples. We highlight that such a general strategy can provide a valuable avenue toward various functional porous crystalline materials.

Proinflammatory T-lymphocytes recruited into the brain and spinal cord mediate multiple sclerosis (MS) and currently there is no cure for MS. IFN-γ-producing Th1 cells induce ascending paralysis in the spinal cord while IL-17-producing Th17 cells mediate cerebellar ataxia. STAT1 and STAT3 are required for Th1 and Th17 development, respectively, and the simultaneous targeting of STAT1 and STAT3 pathways is therefore a potential therapeutic strategy for suppressing disease in the spinal cord and brain. However, the pharmacological targeting of STAT1 and STAT3 presents significant challenges because of their intracellular localization. We have developed a STAT-specific single-domain nanobody (SBT-100) derived from camelids that targets conserved residues in Src homolog 2 (SH2) domains of STAT1 and STAT3. This study investigated whether SBT-100 could suppress experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that SBT-100 ameliorates encephalomyelitis through suppressing the expansion of Th17 and Th1 cells in the brain and spinal cord. Adoptive transfer experiments revealed that lymphocytes from SBT-100-treated EAE mice have reduced capacity to induce EAE, indicating that the immunosuppressive effects derived from the direct suppression of encephalitogenic T-cells. The small size of SBT-100 makes this STAT-specific nanobody a promising immunotherapy for CNS autoimmune diseases, including multiple sclerosis.

Litter distribution significantly affects nutrient cycling, energy transfer, and various ecosystem services. However, little is known about how microtopography affects litter accumulation and distribution on the forest floor. Distribution characteristics of litter stocks at the slope-scale and their relationship with topography and rock exposure rate (RER) in a typical subtropical karst forest in China were determined by measuring the litter stock and RER of 300 grids of1 × 1 m in a 10 × 120 m square on a limestone hill. The results showed that (1) the average litter stock of karst forest was 691.54 ± 332.60 g∙m-2, among which 65.81% was undecomposed litter; (2) the spatial distribution of litter stocks was uneven with moderate variation, presenting five aggregated areas and four sparse areas on the entire slope; (3) there was a significant negative correlation between RER and litter stock (R = −0.37, P

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration–time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans.

Abstract In present work, spectrum of the S-wave fully-heavy tetraquark states $$QQ\bar{Q}\bar{Q}$$ Q Q Q ¯ Q ¯ ( $$Q=c,b$$ Q = c , b ), i.e., $$cc\bar{c}\bar{c}$$ c c c ¯ c ¯ , $$bb\bar{b}\bar{b}$$ b b b ¯ b ¯ , $$cc\bar{b}\bar{b}$$ c c b ¯ b ¯ / $$bb\bar{c}\bar{c}$$ b b c ¯ c ¯ , $$bc\bar{c}\bar{c}$$ b c c ¯ c ¯ / $$cc\bar{b}\bar{c}$$ c c b ¯ c ¯ , $$bb\bar{c}\bar{b}$$ b b c ¯ b ¯ / $$cb\bar{b}\bar{b}$$ c b b ¯ b ¯ , and $$bc\bar{b}\bar{c}$$ b c b ¯ c ¯ are systematically investigated within a nonrelativistic constituent quark model, in which the instanton-induced and one-gluon-exchange interactions are taken into account as the residual spin-dependent hyperfine interaction. Our results show that the states with $$cc\bar{c}\bar{c}$$ c c c ¯ c ¯ and $$bb\bar{b}\bar{b}$$ b b b ¯ b ¯ components could be located around 6500 MeV and 19,200 MeV, respectively. Based on our calculations, the new X(6900) state observed by LHCb may be not a ground $$cc\bar{c}\bar{c}$$ c c c ¯ c ¯ tetraquark state, while it could be an orbitally or radially excited state of $$cc\bar{c}\bar{c}$$ c c c ¯ c ¯ system. On the other hand, the recently reported X(6600) state by CMS and ATLAS can be explained as a ground $$cc\bar{c}\bar{c}$$ c c c ¯ c ¯ tetraquark state with spin-parity $$J^{PC} =0^{++}$$ J PC = 0 + + .

The synthesis of ionic olefin linked threedimensional covalent organic frameworks (3D COFs) is challenging because of the difficulties in forming stable carbon-carbon double bonds. Here, the authors report a general synthesis of an ionic sp2 carbon linked COFs and demonstrate selective capture of ReO4 − ions.

Abstract Spectrum of the low-lying hidden- and double-charm tetraquark states are investigated in a nonrelativistic quark potential model, where the instanton-induced interaction is taken as the residual spin-dependent hyperfine interaction between quarks. The model parameters are fixed by fitting the spectrum of the ground hadron states. Our numerical results show that masses of several presently studied tetraquark states are close to those of the experimentally observed candidates of exotic meson, which indicates that the corresponding compact tetraquark components may take considerable probabilities in those observed exotic states.

IntroductionIL-27 is a heterodimeric cytokine composed of Ebi3 and IL-27p28 and can exert proinflammatory or immune suppressive effects depending on the physiological context. Ebi3 does not contain membrane-anchoring motifs, suggesting that it is a secreted protein while IL-27p28 is poorly secreted. How IL-27p28 and Ebi3 dimerize in-vivo to form biologically active IL-27 is unknown. Major impediment to clinical use of IL-27 derives from difficulty of determining exact amount of bioavailable heterodimeric IL-27 needed for therapy.MethodsTo understand how IL-27 mediates immune suppression, we characterized an innate IL-27-producing B-1a regulatory B cell population (i27-Breg) and mechanisms i27-Bregs utilize to suppress neuroinflammation in mouse model of uveitis. We also investigated biosynthesis of IL-27 and i27-Breg immunobiology by FACS, immunohistochemical and confocal microscopy.ResultsContrary to prevailing view that IL-27 is a soluble cytokine, we show that i27-Bregs express membrane-bound IL-27. Immunohistochemical and confocal analyses co-localized expression of IL-27p28 at the plasma membrane in association with CD81 tetraspanin, a BCR-coreceptor protein and revealed that IL-27p28 is a transmembrane protein in B cells. Most surprising, we found that i27-Bregs secrete IL-27-containing exosomes (i27-exosomes) and adoptive transfer of i27-exosomes suppressed uveitis by antagonizing Th1/Th17 cells, up-regulating inhibitory-receptors associated with T-cell exhaustion while inducing Treg expansion.DiscussionUse of i27-exosomes thus obviates the IL-27 dosing problem, making it possible to determine bioavailable heterodimeric IL-27 needed for therapy. Moreover, as exosomes readily cross the blood-retina-barrier and no adverse effects were observed in mice treated with i27-exosome, results of this study suggest that i27-exosomes might be a promising therapeutic approach for CNS autoimmune diseases.