A Dual-Mechanism Based Nutrient Partitioning Nanoregulator for Enhanced Immunotherapy against Anti-PD-1 Resistant Tumors.

Competitive consumption of nutrients between rapidly proliferating cancer cells and T cells results in an immunosuppressive tumor microenvironment (TME) and nutrient deprivation of T cells, which can cause low response rate and resistance to immunotherapies. In this study, we proposed a dual-mechanism based nutrient partitioning nanoregulator (designated as DMNPN), which can simultaneously regulate the immunosuppressive TME and enhance T cell nutrient availability. DMNPN consists of a charge-reversal biodegradable mesoporous silica, encapsulating glycolysis inhibitor lonidamine, and small interfering RNA against glutaminase.

Advances and perspectives of proteolysis targeting chimeras (PROTACs) in drug discovery.

Proteolysis-targeting chimeras (PROTACs), bifunctional molecules consisting of a ligand of protein of interest (POI), an E3 ligase ligand and a linker, have been developed to hijack the ubiquitin-proteasome system (UPS) to induce different POIs degradation. Currently, the first oral PROTACs (ARV-110 and ARV-471) have shown encouraging efficacy in clinical trials of prostate and breast cancer treatment, which turns a new avenue for the development of PROTAC research. In this review, we focus on a detailed summary of the latest progress of PROTACs and elucidate the advantages of PROTACs technology.

Notch-mediated lactate metabolism regulates MDSC development through the Hes1/MCT2/c-Jun axis.

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) play critical roles in tumorigenesis. However, the mechanisms underlying MDSC and TAM development and function remain unclear. In this study, we find that myeloid-specific activation of Notch/RBP-J signaling downregulates lactate transporter MCT2 transcription via its downstream molecule Hes1, leading to reduced intracellular lactate levels, blunted granulocytic MDSC (G-MDSC) differentiation, and enhanced TAM maturation.

Colloidal CdS sensitized nano-ZnO/chitosan hydrogel with fast and efficient photocatalytic removal of congo red under solar light irradiation.

Colloidal CdS sensitized nano-ZnO/chitosan (CdS@n-ZnO/CS) hydrogel was prepared and characterized extensively by XRD, SEM-EDS, TEM, UV-Vis DRS, FT-IR and TGA. The photocatalytic activity of CdS@n-ZnO/CS was evaluated with the photodegradation of congo red (CR) as an organic pollutant under solar light irradiation. The influences of initial dye concentration, catalyst dosage, recycling runs, and radical scavenger on decolorization of CR by CdS@n-ZnO/CS were investigated.

Highly Chemo- and Enantioselective Hydrogenation of 2-Substituted-4-oxo-2-alkenoic Acids.

The highly chemo- and enantioselective hydrogenation of ()-2-substituted-4-oxo-2-alkenoic acids was established for the first time using the Rh/JosiPhos complex, affording a series of chiral -substituted--keto acids with excellent results (up to 99% yield and >99% ) and high efficiency (up to 3000 TON). In addition, the importance of this methodology was further demonstrated by a concise and gram-scale synthesis of the anti-inflammatory drug ()-flobufen.

Concise asymmetric synthesis of two natural oxacyclododecindione-type macrolactones from industrial waste.

()-5-Methyl-tetrahydropyran-2-one 1 is a by-product in the production of key intermediates of steroidal hormones. Asymmetric synthesis of natural oxacyclododecindione-type macrolactones 2 and 3 has been realized for the first time from ()-1 in seven and eight steps with 37% and 27% overall yield, respectively.

Highly Regio- and Enantioselective Hydrogenation of Conjugated α-Substituted Dienoic Acids.

Highly regio- and enantioselective hydrogenation of conjugated -substituted dienoic acids was realized for the first time using Trifer-Rh complex, providing a straightforward method for the synthesis of chiral -substituted -unsaturated acids. DFT calculations revealed NH-O hydrogen bonding interaction is formed to stabilize the transition state and the coordination of 4,5-double bond to Rh(III) center would facilitate the reductive elimination process. This hydrogenation provided a gram-scale synthesis of the precursor of sacubitril.

Synthesis and anti-tyrosinase mechanism of the substituted vanillyl cinnamate analogues.

This study aimed to synthesize and screen tyrosinase inhibitors for delay fruit browning. A series of vanillyl cinnamate analogues were designed and synthesized by simple processes, and the inhibitory effects of all the synthesized derivatives on mushroom tyrosinase were evaluated. In the enzymatic activity test, compounds 21, 22, and 26 had significant (P < 0.

Bifunctional ferrocene-based squaramide-phosphine as an organocatalyst for highly enantioselective intramolecular Morita-Baylis-Hillman reaction.

This work demonstrates that, in accord with metal catalysis, ferrocene could be an excellent scaffold for organocatalysts. The simple and easily accessible bifunctional ferrocene-based squaramide-phosphine shows high enantioselectivity in the intramolecular Morita-Baylis-Hillman reaction of 7-aryl-7-oxo-5-heptenals, giving a variety of 2-aroyl-2-cyclohexenols in up to 96% ee.

Autophagy stimulates apoptosis in HER2-overexpressing breast cancers treated by lapatinib.

HER2-overexpressing breast cancers often show hyperactivation of the HER2/AKT/mTOR signaling pathway. Lapatinib is an oral dual tyrosine kinase inhibitor (TKI) that targets both EGFR and HER2 to inhibit the proliferation of breast cancer cells. However, it is obscure whether and how lapatinib could induce autophagy in breast cancer cells, an important cell response with drug treatment.

(R C,S Fe)-1-[3,5-Bis(trifluoro-meth-yl)phen-yl]-3-{1-[2-(diphenyl-phosphan-yl)ferro-cen-yl]eth-yl}thio-urea (unknown solvate).

In the molecule of the the title compound, [Fe(C5H5)(C28H22F6N2PS)], the absolute configuration is R C ,SFe . The dihedral angle between the trifluoro-methyl-substituted phenyl ring and the thio-urea plane is 41.8 (9)°.

Overview on LFG projects in China.

Since the first landfill gas (LFG) power plant in China was built in 1998, by now more than 10years have passed. In this period the LFG utilization process has progressed greatly in China. An overall review of the process is presented in this paper, which includes the background of policies, the information about the approval procedure of LFG projects, and the theoretical methods used to estimate the amount of LFG's generation.

5-Methyl 3-(2-methyl-prop-3-yl) 2,6-di-methyl-4-(2-nitro-sophen-yl)pyridine-3,5-dicarboxyl-ate.

In the title compound, C(20)H(22)N(2)O(5), a photo-degradation product of the hypertension drug nisoldipine, the dihedral angle between the nitro-sophenyl ring and the pyridine ring is 75.7 (3)°. In the crystal structure, weak C-H⋯O hydrogen bonds help to establish the packing.

3-Isobutyl 5-methyl 2,6-dimethyl-4-(2-nitro-phen-yl)pyridine-3,5-dicarboxyl-ate.

The title nitro-phenyl pyridine compound, C(20)H(22)N(2)O(6) was synthesized as a degradation product of the hypertension medication nisoldipine. The dihedral angle between the nitro-substituted phenyl ring and the pyridine ring is 75.5 (4)°.