Somatostatin receptor 2 targeting peptide modifications for peptide-drug conjugate treatment of small cell lung cancer.

Peptide-drug conjugate (PDC) represents a special therapeutic strategy to enhance drug delivery by targeting tumor cell receptors while minimizing off-target effects. Comparing the antibody-drug conjugate (ADC), the targeting peptide constitutes the pivotal component of PDC, especially with easy optimization of peptides to promote their in vivo stability, and with the agonist stimulated GPCR internalization to facilitate drug distribution into tumor cell plasma. Herein, we have optimized a highly stable peptide molecule LanTC targeting somatostatin receptor 2 (SSTR2), through amino acid substitution and disulfide bond modification from an FDA proved peptide drug Lanreotide.

Construction of universal taper equation of in different climatic regions.

Based on 234 tree samples from 78 sampling plots across three regions, including Liao-ning, Hubei, and Gansu provinces, we selected the optimal one among the six commonly used taper equations in forestry research to construct a basic model, a climate response model, and a nonlinear mixed-effects model suitable for different climatic regions with the climatic factors being added in an exponential form. We further investigated the stem form indices of in different regions, analyzed the differences in stem form responses to climatic variables, and selected the optimal universal equation based on the fitting accuracy of the three models. The results showed that Kozak model had the best universality and was the optimal basic model.

[Construction of biomass models for understory shrubs and tree saplings in Fenglin County, Heilongjiang Province, China.].

Shrubs and tree saplings are important components of understory in natural forests, possessing rich species diversity and broad ecological adaptability. They play a key role in soil moisture retention, water conservation, and wind and sand prevention. However, current research has mostly focused on the interactions between the tree layer and understory, with less attention on the growth dynamics, biomass renewal, and environmental adaptability of understory.

Passive all-optical isolator based on spatial self-phase modulation.

Optical isolators are essential devices that enable light propagation in a single direction, finding widespread applications in fields such as optical communication and optical computing. A prerequisite for these devices to achieve optical nonreciprocity (ONR) is the violation of Lorentz reciprocity. Traditional approaches to ONR rely on external magnetic fields, spatiotemporal modulation, or nonlinear optical effects.

Construction of universal equations for knot attributes of three coniferous species.

We constructed base model, dummy variable model, and mixture model with three variables including knot diameter, loose knot length, and sound knot length with three typical coniferous species, , , and var. , from the Linkou Forestry Bureau and Mengjiagang forest farm in Heilongjiang Province in 2020. We analyzed the differences in knot properties among different tree species and simplified the modeling work.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking.

Involvement of the thalamic reticular nucleus in prepulse inhibition of acoustic startle.

Thalamic reticular nucleus (TRN) is a group of inhibitory neurons surrounding the thalamus. Due to its important role in sensory information processing, TRN is considered as the target nucleus for the pathophysiological investigation of schizophrenia and autism spectrum disorder (ASD). Prepulse inhibition (PPI) of acoustic startle response, a phenomenon that strong stimulus-induced startle reflex is reduced by a weaker prestimulus, is always found impaired in schizophrenia and ASD.

Acute EPA-induced learning and memory impairment in mice is prevented by DHA.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid, has been widely used to prevent cardiovascular disease (CVD) and treat brain diseases alone or in combination with docosahexaenoic acid (DHA). However, the impact of EPA and DHA supplementation on normal cognitive function and the molecular targets of EPA and DHA are still unknown. We show that acute administration of EPA impairs learning and memory and hippocampal LTP in adult and prepubescent mice.

Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice.

Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless.

Astrocytic GABA Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF.

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD.

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized.

Iron-Catalyzed Regioselective α-C-H Alkylation of N-Methylanilines: Cross-Dehydrogenative Coupling between Unactivated C(sp)-H and C(sp)-H Bonds via a Radical Process.

The iron-catalyzed α-C-H alkylation of N-methylanilines without any directing group by cross-dehydrogenative coupling between unactivated C(sp)-H and C(sp)-H bonds has been established for the first time, which provides a good complement to C(sp)-H activation reactions and expands the field of Fe-catalyzed C-H functionalizations. Many different C(sp)-H bonds in cyclic alkanes, cyclic ethers, and toluene derivatives can be used as coupling partners. Mechanistic investigations including the radical reaction process, the main role of various reagents, and the kinetic isotope effect experiment were also described.

Nickel-Catalyzed Cross-Dehydrogenative Coupling of α-C(sp)-H Bonds in N-Methylamides with C(sp)-H Bonds in Cyclic Alkanes.

A nickel-catalyzed cross-dehydrogenative coupling reaction of α-C(sp)-H bonds in N-methylamides with C(sp)-H bonds from cyclic alkanes has been developed, which offers a cheap transition-metal-catalyzed C-H activation method for amides without the requirement for any extraneous directing group. This new strategy is highly selective and tolerates a variety of functional groups. Mechanistic investigations into the reaction process are also described in detail.

Cobalt(ii)-catalyzed regioselective C-H halogenation of anilides.

A cobalt-catalyzed regioselective C-H halogenation methodology is reported herein. The highlight of this work is the highly selective C-H functionalization of anilides, which results in high-yielding, versatile, and practical halogenated products. Thereby, brominations, chlorinations and iodinations of many electron-rich and electron-deficient anilides were achieved in a highly selective fashion.

Nickel-catalyzed product-controllable amidation and imidation of sp C-H bonds in substituted toluenes with sulfonamides.

A nickel-catalyzed product-controllable imidation and amidation of sp C-H bonds in substituted toluenes with sulfonamides were developed. Based on the change of the reaction time and atmosphere from N to O, this reaction proceeded in high yields and excellent selectivity under different conditions. Mechanistic details were also described.

Immunotherapeutic Effects of Dendritic Cells Pulsed with a Coden-optimized HPV 16 E6 and E7 Fusion Gene in Vivo and in Vitro.

Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer.

[Anti-adenovirus neutralizing antibodies and Gag-specific cellular immune responses in Macaca fascicularis immunized with Ad5-HIVgag].

Objective: To observe the level of anti-adenovirus neutralizing antibodies and Gag specific cellular immune responses in Macaca fascicularis immunized with different dosage of recombinant adenovirus vaccine Ad5-HIVgag by repeated intramuscular injection.

Methods: The Macaca fascicularis were randomly divided into four groups of 6. Different amount of the purified Ad5-HIVgag (0.

Transforming activity of a novel mutant of HPV16 E6E7 fusion gene.

An optimized recombinant HPV16 E6E7 fusion gene (HPV16 ofE6E7) was constructed according to codon usage for mammalian cell expression, and a mutant of HPV16 ofE6E7 fusion gene (HPV16 omfE6E7) was generated by site-directed mutagenesis at L57G, C113R for the E6 protein and C24G, E26G for the E7 protein for HPV16 ofE6E7 [patent pending (CN 101100672)]. The HPV16 omfE6E7 gene constructed in this work not only lost the transformation capability to NIH 3T3 cells and tumorigenicity in SCID mice, but also maintained very good stability and antigenicity. These results suggests that the HPV16 omfE6E7 gene should undergo further study for application as a safe antigen-specific therapeutic vaccine for HPV16-associated tumors.

A novel strategy to assemble colloidal gold nanoparticles at the water-air interface by the vapor of formic acid.

We report a novel strategy on the controlled assembly of gold nanoparticles (NPs) at the air-water interface by designing a concentration gradient of electrolytes utilizing volatile weak acidic electrolytes. Films of close-packed Au NPs can be facilely obtained by exposing citrate-protected gold colloids to the vapor of formic acid for several hours in an airtight desiccator at room temperature. Both the higher interfacial concentration of formic acid and the buffer effect of citrate solution play the key roles in the assembly.

[In vitro pharmacodynamics study of an anti-HIV Chinese herbal formulation].

AIDS caused by HIV-1, is a major threat to human being. An anti-HIV formulation from Chinese herbs, so called "Qu Du Zeng Ning", have been recently developed. In this work, the pharmacodynamics of the formulation in vitro was studied.

[Variation of the V3 loop tip motifs and primary drug resistance of HIV-1 strains].

Objective: To study the characteristics of the variation of the V3 loop tip motifs and the drug resistance in the primary treatment patients.

Methods: The partial region of the HIV-1 env and pol gene in 51 samples was amplified by nested polymerase chain reaction (PCR) ,purified products were cloned into the vectors, the obtained were analyzed by MEGA soft wares.

Results: The V3 loop tip motifs had four types in our study (GPGR, GPGQ, GPGK, GQGR); the study on the drug resistance in primary treatment patients, showed that there were not major resistance associated with PI, and the resistance were minor mutations in protease gene.