Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells.

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.

Activation of cyclopentadiene derivatives by an α-diimine-ligated Mg-Mg-bonded compound.

Heteroleptic, bimetallic (Mg/K) cyclopentadienyl complexes (2-4) were synthesized by the reaction of the Mg-Mg-bonded compound [K(THF)3]2[LMg-MgL] (1, L = [(2,6-iPr2C6H3)NC(CH3)]22-) with cyclopentadiene derivatives, 6,6-dimethylfulvene, 6-(dimethylamino)fulvene, or 1,2,3,4-tetramethyl-1,3-cyclopentadiene. The reactions proceed through diverse pathways, including hydrogen abstraction, C-C coupling, and dehydrogenation, depending on the property of the polyene substrate, thus providing an access to alkali/alkaline earth metal cyclopentadienyl complexes.

Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.

Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-ß and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-ß and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments.

Effects of high-temperature stress on gene expression related to photosynthesis in two jujube (Ziziphus jujuba Mill.) varieties.

Elevated temperatures critically impact crop growth, development, and yield, with photosynthesis being the most temperature-sensitive physiological process in plants. This study focused on assessing the photosynthetic response and genetic adaptation of two different heat-resistant jujube varieties 'Junzao' (J) and 'Fucuimi' (F), to high-temperature stress (42°C Day/30°C Night). Comparative analyses of leaf photosynthetic indices, microstructural changes, and transcriptome sequencing were conducted. Results indicated superior high-temperature adaptability in F, evidenced by alterations in leaf stomatal behavior - particularly in J, where defense cells exhibited significant water loss, shrinkage, and reduced stomatal opening, alongside a marked increase in stomatal density. Through transcriptome sequencing 13,884 differentially expressed genes (DEGs) were identified, significantly enriched in pathways related to plant-pathogen interactions, amino acid biosynthesis, starch and sucrose metabolism, and carbohydrate metabolism. Key findings include the identification of photosynthetic pathway related DEGs and HSFA1s as central regulators of thermal morphogenesis and heat stress response. Revealing their upregulation in F and downregulation in J. The results indicate that these genes play a crucial role in improving heat tolerance in F. This study unveils critical photosynthetic genes involved in heat stress, providing a theoretical foundation for comprehending the molecular mechanisms underlying jujube heat tolerance.

Biomimetic Charge-Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in water.

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO43-) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge-neutral tripodal hexaurea receptors (L1 - L4), which were equipped with morpholine and PEG terminal groups to enhance their solubility in water, were synthesized to enable the pH-triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO43- anion in a 1:1 ratio via hydrogen bonds in 100% water solutions, with L1 exhibiting the highest binding constant (1.2´103 M-1). These represent the first neutral anion ligands to bind phosphate in 100% water and demonstrate the potential for phosphate capture and release in water through pH-triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.

Impact of flaxseed gum on the aggregate structure, pasting properties, and rheological behavior of waxy rice starch.

This study examines the effects of flaxseed gum (FG) on the aggregate structure, pasting and rheological properties of waxy rice starch (WRS). Results display an increase in the ordered molecular structure (R1047/1024), relative crystallinity (RC), compactness (α), and microphase heterogeneity (ε, density degree of nanoaggregates, from 3.52 to 4.23) for WRS-FG complexes. These suggested FG facilitated the development of more organized molecular and crystalline structures of WRS, accompanied by the formation of ordered nanoaggregates with higher density (i.e., nano-aggregation structure). Also, FG addition resulted in the formation of enhanced gel network structure characterized by thicker layer walls and more uniform pores. These structural transformations contributed to a rise in gelatinization temperature (To, from 56.90 °C to 62.10 °C) and enthalpy (ΔH), as well as alterations in paste viscosities (PV, from 1285.00 mPa·s to 1734.00 mPa·s), and the rigidity of network structure (e.g., decreased loss tangent). These results indicate that FG could effectively regulate the techno-functional properties of WRS by rationally controlling the starch intrinsic structures of starch. And this study may improve the pasting and gelling properties of starch, thus driving the development of high-quality starchy foods and prolonging their shelf life, especially for glutinous rice flour products.

Discovery of potent and novel dual NAMPT/BRD4 inhibitors for efficient treatment of hepatocellular carcinoma.

The NAPRT-induced increase in NAD+ levels was proposed as a mechanism contributing to hepatocellular carcinoma (HCC) resistance to NAMPT inhibitors. Thus, concurrently targeting NAMPT and NAPRT could be considered to overcome drug resistance. A BRD4 inhibitor downregulates the expression of NAPRT in HCC, and the combination of NAMPT inhibitors with BRD4 inhibitors simultaneously blocks NAD+ generation via salvage and the PH synthesis pathway. Moreover, the combination of the two agents significantly downregulated the expression of tumor-promoting genes and strongly promoted apoptosis. The present work identified various NAMPT/BRD4 dual inhibitors based on the multitargeted drug rationale. Among them, compound A2, which demonstrated the strongest effect, exhibited potent inhibition of NAMPT and BRD4 (IC50 = 35 and 58 nM, respectively). It significantly suppressed the growth and migration of HCC cells and facilitated their apoptosis. Furthermore, compound A2 also manifested a robust anticancer effect in HCCLM3 xenograft mouse models, with no apparent toxic effects. Our findings in this study provide an effective approach to target NAD+ metabolism for HCC treatment.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis.

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.

tiRNA-Val-CAC-2 interacts with FUBP1 to promote pancreatic cancer metastasis by activating c­MYC transcription.

Cumulative studies have established the significance of transfer RNA-derived small RNA (tsRNA) in tumorigenesis and progression. Nevertheless, its function and mechanism in pancreatic cancer metastasis remain largely unclear. Here, we screened and identified tiRNA-Val-CAC-2 as highly expressed in pancreatic cancer metastasis samples by tsRNA sequencing. We also observed elevated levels of tiRNA-Val-CAC-2 in the serum of pancreatic cancer patients who developed metastasis, and patients with high levels of tiRNA-Val-CAC-2 exhibited a worse prognosis. Additionally, knockdown of tiRNA-Val-CAC-2 inhibited the metastasis of pancreatic cancer in vivo and in vitro, while overexpression of tiRNA-Val-CAC-2 promoted the metastasis of pancreatic cancer. Mechanically, we discovered that tiRNA-Val-CAC-2 interacts with FUBP1, leading to enhanced stability of FUBP1 protein and increased FUBP1 enrichment in the c-MYC promoter region, thereby boosting the transcription of c-MYC. Of note, rescue experiments confirmed that tiRNA-Val-CAC-2 could influence pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight a potential novel mechanism underlying pancreatic cancer metastasis, and suggest that both tiRNA-Val-CAC-2 and FUBP1 could serve as promising prognostic biomarkers and potential therapeutic targets for pancreatic cancer.

Triplane technique for breast reconstruction after breast cancer surgery: A case series report.

RATIONALE: Implant-based breast reconstruction is an important method for post-mastectomy breast reconstruction. Currently, the most commonly used technique is the biplane technique. However, the high rate of postoperative complications, the inability of pockets to accommodate larger implants, and the expensive costs of biological mesh make the development of new surgical methods urgent. The triplane technique for breast reconstruction is an ideal candidate method. PATIENT CONCERNS: The main local symptoms were breast lump, abnormal breast skin, nipple discharge, and abnormal nipple or areola in 24 patients. DIAGNOSES: The study included 24 female patients who underwent breast reconstruction using the triplane technique after radical breast cancer surgery. INTERVENTIONS: The surgical procedure involved measuring the dimensions of the breast, designing the incision, and creating a pocket for the implant using the triplane technique, which includes the pectoralis major muscle, the pectoralis major fascia continuing to the rectus abdominis fascia, and the latissimus dorsa muscle fascia continuing to the rectus abdominis fascia. Postoperative follow-up included regular assessments of pain and evaluation of breast appearance. OUTCOMES: No cases of postoperative infection were observed in all patients. During the 1-year follow-up period after surgery, 5 patients (20.8%) who needed radiotherapy after mastectomy for cancer showed slight darkening of skin flap pigment after using the triplane technique implant. No cases of exposure or infection of the expanders were reported, and 1 patient underwent expander replacement with a permanent prosthesis. All patients expressed satisfaction with the reconstructed breast shape. The 10 patients (41.7%) experiencing postoperative swelling and pain. However, the pain gradually subsided during the postoperative recovery period. No cases of local recurrence or distant metastasis of breast cancer were observed during the 1-year-follow-up period. LESSONS: The triplane technique for breast reconstruction after breast cancer surgery provides good implant coverage, reduces the risk of complications, and is cost-effective.

Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer.

Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.

The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs.

BACKGROUND: A growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines. PURPOSE: Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear. METHODS: Stool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and ß diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed. RESULT: At the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4+CD45RO+CCR7+CXCR5+central memory Tfh cells and CD4+CD45RO+CCR7-CXCR5+effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19+CD27+IgD+pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19+CD27+IgD-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19+CD27+IgD+ pre-switched memory B cells but positively correlated with CD4+CD45RO+CCR7-CXCR5+effector memory Tfh and CD19+CD27+IgD-switched memory B cells in patients with RA treated with DMARDs. CONCLUSION: The gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.

Meta-analysis of FOXP3 polymorphisms and recurrent spontaneous abortion susceptibility.

BACKGROUND: The polymorphisms of the FOXP3 gene may mediate abnormalities in Tregs, leading to an imbalance in maternal-fetal immune tolerance and ultimately resulting in recurrent spontaneous abortion (RSA). This meta-analysis aims to assess the potential association between FOXP3 polymorphisms and susceptibility to RSA using five specific single nucleotide polymorphisms (SNPs). MATERIALS AND METHODS: By conducting a comprehensive search across databases such as EMBASE, PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and CBM, we identified suitable studies for inclusion in the meta-analysis. The data extracted from these studies were subjected to analysis using Stata SE 15. To assess the degree of association, we utilized the odds ratio (OR) along with its corresponding 95% confidence intervals (CI). Five specific single nucleotide polymorphisms (SNPs) were employed in assessing the connection between FOXP3 gene polymorphisms and RSA. RESULTS: The meta-analysis demonstrated a significant association between several polymorphisms (rs3761548, rs2232365, rs2232368, rs2280883, and rs2294021) and susceptibility to RSA. Conversely, the FOXP3 rs5902434 polymorphism was not associated with susceptibility to RSA. CONCLUSION: Our meta-analysis suggests that these genetic variations within the FOXP3 gene might play a role in the progression of RSA disease. Meanwhile, large-scale studies that consider multiple factors are needed to validate this finding.

Research progress of LSD1-based dual-target agents for cancer therapy.

Lysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1 inhibitors synergistically improve the efficacy of additional antitumor drugs, which encourages numerous medicinal chemists to innovate and develop new-generation LSD1-based dual-target agents. This review discusses the theoretical foundation of the design of LSD1-based dual-target agents and summarizes their possible applications in treating cancers.

Incorporation of an Anion-Coordinated Triple Helicate into a Thin Film for Choline Recognition in an Aqueous System.

Functional thin films, being fabricated by incorporating discrete supramolecular architectures, have potential applications in research areas such as sensing, energy storage, catalysis, and optoelectronics. Here, we have determined that an anion-coordinated triple helicate can be solution-processed into a functional thin film by incorporation into a polymethyl methacrylate (PMMA) matrix. The thin films fabricated by the incorporation of the anion-coordinated triple helicate show multiple optical properties, such as fluorescence, CD, and CPL. In addition, the film has the ability to recognize choline and choline derivatives in a water system. The successful recognition of Ch+ by the film represents the first example of utilizing 'aniono'-supramolecular architectures for biomolecule detection in aqueous solution and opens up a new route for designing biocompatible functional materials.

Effects of early enteral nutrition in patients with severe burns: A systematic review.

BACKGROUND: Nutritional problems in the early stages of severe burns are prominent and seriously affect the clinical outcomes of patients. Our aim is to analyze the effects of early enteral nutrition (EEN) in patients with severe burns. METHODS: In this study, relevant articles were searched in 8 English and Chinese data, with a time limit from the creation of the database to June 2023. Two researchers independently completed the search, screening and quality assessment of the articles. We conducted a systematic review and meta-analysis of randomized controlled trials that examined EEN therapy in people with severe burns. We compared the effects of EEN and non-EEN therapy in severely burned patients. The outcomes were mortality, gastrointestinal complications, nutritional indicators, gastrointestinal hormones, sepsis, length of hospital stay and wound healing time. Categorical variables were expressed as OR and 95% CI was calculated, and continuous variables were expressed as MD and 95% CI was calculated. The protocol for this systematic review was registered in PROSPERO on May 12, 2023 (identifier CRD42023422895). RESULTS: Nineteen studies with a total of 1066 participants met the inclusion criteria. When comparing EEN therapy with non-EEN therapy, the experiment group had significantly lower mortality [OR = 0.39, 95% CI (0.20, 0.74), P = .004], lower wound healing time [MD = -10.77, 95% CI (-13.66,-7.88), P < .00001], fewer gastrointestinal complications [OR = 0.18, 95% CI (0.09, 0.36), P < .00001], lower rates of gastrointestinal hemorrhage [OR = 0.12, 95% CI (0.04, 0.36), P = .0001], lower rates of sepsis [OR = 0.40, 95% CI (0.24, 0.66), P = .0005], shorter length of hospital stay [MD = -12.08, 95% CI (-13.61, 9.19-10.56), P < .00001], and higher prealbumin levels [MD = 29.04, 95% CI (21.98, 36.10), P < .00001], higher total albumin levels [MD = 6.74, 95% CI (4.29, 9.19), P < .00001], and gastrin levels [MD = 15.93, 95% CI (10.12, 21.73), P < .00001]. However, there was no significant difference in albumin between the 2 groups [MD = 2.62, 95% CI (-0.30, 5.55), P = .08] or motilin levels [MD = 12.48, 95% CI (-43.59, 68.56), P = .66]. CONCLUSIONS: EEN plays an important role in the rehabilitation of patients with severe burns. EEN is beneficial to reduce complications and the length of hospital stay, maintain organ function, optimize the nutritional status of patients, promote wound healing, and improve the survival rate of patients.

One-Electron (2c/1e) Tin···Tin Bond Stabilized by ortho-Phenylenediamido Ligands.

Odd-electron bonds, i.e., the two-center, three-electron (2c/3e), or one-electron (2c/1e) bonds, have attracted tremendous interest owing to their novel bonding nature and radical properties. Herein, complex [K(THF)6][LSn:···Sn:L] (1), featuring the first and unsupported 2c/1e Sn···Sn σ-bond with a long distance (3.2155(9) Å), was synthesized by reduction of stannylene [LSn:] (L = N,N-dpp-o-phenylene diamide) with KC8. The one-electron Sn-Sn bond in 1 was confirmed by the crystal structure, DFT calculations, EPR spectroscopy, and reactivity studies. This compound can be viewed as a stabilized radical by delocalizing to two metal centers and can readily mediate radical reactions such as C-C coupling of benzaldehyde.