Exploring the Biomedical Potential of Terpenoid Alkaloids: Sources, Structures, and Activities.

Terpenoid alkaloids are recognized as a class of compounds with limited numbers but potent biological activities, primarily derived from plants, with a minor proportion originating from animals and microorganisms. These alkaloids are synthesized from the same prenyl unit that forms the terpene skeleton, with the nitrogen atom introduced through ß-aminoethanol, ethylamine, or methylamine, leading to a range of complex and diverse structures. Based on their skeleton type, they can be categorized into monoterpenes, sesquiterpenes, diterpenes, and triterpene alkaloids. To date, 289 natural terpenoid alkaloids, excluding triterpene alkaloids, have been identified in studies published between 2019 and 2024. These compounds demonstrate a spectrum of biological activities, including anti-inflammatory, antitumor, antibacterial, analgesic, and cardioprotective effects, making them promising candidates for further development. This review provides an overview of the sources, chemical structures, and biological activities of natural terpenoid alkaloids, serving as a reference for future research and applications in this area.

Ingenious Modulation of Third-Order Nonlinear Optical Response of Zr-MOFs through Defect Engineering Based on a Mixed-Linker Strategy.

Defect engineering plays a pivotal role in regulating electronic structure and facilitating charge transfer, yielding captivating effects on third-order nonlinear optical (NLO) properties. In this work, we utilized a mixed-linker strategy to intentionally disrupt the initial periodic arrangement of UiO-66 and construct defects. Specifically, we incorporated tetrakis(4-carboxyphenyl)porphyrin (TCPP) with an exceptionally electron-rich delocalization system into the framework of UiO-66 using a one-pot solvothermal method, ingeniously occupying the partial distribution sites of the Zr6 clusters. Compared to UiO-66, the NLO absorption and refraction performance of TCPP/UiO-66 were significantly improved. Additionally, due to the presence of nitrogen-rich sites that can accommodate metal ions in the porphyrin ring of TCPP, Co(II), Ni(II), Cu(II), and Zn(II) are introduced into TCPP/UiO-66, extending the d-π conjugation effect to further regulate the defects. The NLO absorption behavior transforms saturation absorption (SA) to reverse saturation absorption (RSA), while the refraction behavior shifts from self-defocusing to self-focusing. This work shows that defects can effectively regulate the electronic structure, while TCPP plays a crucial role in significantly enhancing electron delocalization.

Mechanisms of Sepsis-Induced Acute Lung Injury and Advancements of Natural Small Molecules in Its Treatment.

Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.

Research Progress on Sesquiterpene Compounds from Artabotrys Plants of Annonaceae.

Artabotrys, a pivotal genus within the Annonaceae family, is renowned for its extensive biological significance and medicinal potential. The genus's sesquiterpene compounds have attracted considerable interest from the scientific community due to their structural complexity and diverse biological activities. These compounds exhibit a range of biological activities, including antimalarial, antibacterial, anti-inflammatory analgesic, and anti-tumor properties, positioning them as promising candidates for medical applications. This review aims to summarize the current knowledge on the variety, species, and structural characteristics of sesquiterpene compounds isolated from Artabotrys plants. Furthermore, it delves into their pharmacological activities and underlying mechanisms, offering a comprehensive foundation for future research.

Third-Order Nonlinear Optical Modulation Behavior of Photoresponsive Bimetallic MOFs.

Bimetallic metal-organic frameworks (MOFs) capable of sensing external stimuli will provide more possibilities for further regulating third-order nonlinear optical (NLO) properties. In this work, we synthesized bimetallic MOFs (ZnCu-MOF and ZnCd-MOF) through central metal exchange using a photoresponsive Zn-MOF as a precursor. Compared with Zn-MOF, both ZnCu-MOF and ZnCd-MOF exhibit significantly enhanced third-order NLO absorption properties. This is mainly attributed to the introduction of metal ions with different electron configurations that can adjust the bandgap of MOFs and enhance electron delocalization, thus promoting electron transfer. Interestingly, the bimetallic MOFs show a transition from reverse saturation absorption (RSA) to saturation absorption (SA) after exposure to ultraviolet irradiation, as they retain the properties of directional photogenerated electron transfer. Photoresponsive bimetallic MOFs not only have the effect of bimetallic modulation of electronic structures but also have the characteristics of photoinduced electron transfer, exhibiting diversified optical properties. These findings provide a novel method for the development of multifunctional NLO materials.

A cellulosic multi-bands fluorescence probe for rapid detection of pH and glutathione.

The detection of pH and glutathione (GSH) is positively significant for the cell microenvironment imaging. Here, to assess the pH value and the concentration of GSH efficiently and visually, a cellulose-based multi-bands ratiometric fluorescence probe was designed by assembling MnO2-modified cellulose gold nanoclusters, fluorescein isothiocyanate-grafted cellulose nanocrystals (CNCs) and protoporphyrin IX-modified CNCs. The probe exhibits GSH-responsive, pH-sensitive and GSH/pH-independent fluorescent properties at 440 nm, 520 nm, and 633 nm, respectively. Furthermore, the probe identifies GSH within 4 s by degrading MnO2 into Mn2+ in response to GSH. Ingeniously, the green fluorescence of the probe at 520 nm was decreased with pH, and the red fluorescence at 633 nm remained stable. Therefore, the probe displayed distinguishing fluorescence colors from pink to blue and from green to blue for the synchronous detection of pH and GSH concentration within 4 s. The design strategy provides insights to construct multi-bands fluorescence probes for the rapid detection of multiple target analytes.

Transformation of SBUs and Synergy of MOF Host-Guest in Single Crystalline State: Ingenious Strategies for Modulating Third-Order NLO Signals.

Central metal exchange can innovatively open the cavity of metal-organic frameworks (MOFs) by alternating the framework topology. Here, the single-crystal-to-single-crystal (SC-SC) transformation is reported from a Co-based MOF {[Co1.25 (HL)0.5 (Pz-NH2 )0.25 (µ3 -O)0.25 (µ2 -OH)0.25 (H2 O)]·0.125 Co·0.125 L·10.25H2 O}n (Co-MOF, L = 5,5'-(1H-2,3,5-triazole-1,4-diyl)diisophthalic acid) into two novel MOF materials, {[Cu1.75 L0.75 (Pz-NH2 )0.125 (µ3 -O)0.125 (µ2 -OH)0.25 (H2 O)0.375 ]•3CH3 CN}n (Cu-MOF) and {[Zn1.75 L0.625 (Pz-NH2 )0.25 (µ3 -O)0.25 (µ2 -O)0.25 (H2 O)1.25 ]•4CH3 CN}n (Zn-MOF), through exchanging the Co2+ in the MOF into Cu2+ or Zn2+ , respectively. The free Co2+ and L4- in the Co-MOF channels fuse with the skeleton during the Co→Cu and Co→Zn exchange processes, leading to the expansion of the channel space and the transformation of the secondary building units (SBUs) to form an adjustable skeleton. The nonlinear optical response results show that the MOFs generated by the exchange of the central metal exhibit different saturable absorption and the self-focusing effect. In addition, loading polypyrrole (PPy) into the MOFs can not only improve the stability of the MOFs but also further optimize the nonlinear optical behavior. This work suggests that SC-SC central metal exchange and the introduction of polymer molecules can tune the nonlinear optical response, which provides a new perspective for the future study of nonlinear optical materials.

[Effect of deep needling "Tianshu" (ST25) on colonic motility in rats with slow transit constipation].

OBJECTIVE: To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC．. METHODS: Fifty male Wistar rats were selected and randomly divided into control，STC model，conventional acupuncture，deep needling group 1 and deep needling group 2 groups，with 10 rats in each group．The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage．EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days．Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry. RESULTS: Compared with the control group，the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased (P<0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group (P<0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit (P<0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain (P<0.05), lowering the amplitude of EMG of the gut smooth muscle (P<0.05) and in increasing the frequency of EMG (P<0.05) and the expressions of SP and c-kit (P<0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group (P>0.05), except the excretion time of the first black stool grain (P<0.05). CONCLUSION: Deep needling at ST25 at depth of 4.5 mm and 10 mm，especially at depth of 10 mm，has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.

Tailoring and application of a multi-responsive cellulose nanofibre-based 3D nanonetwork wound dressing.

The rapid loss of drugs and the weak curative effects due to cyclical urination are the main reasons why wound heal with difficulty after bladder tumour resection. Here, a bioinspired cellulose nanofibre (CNF)-based magnetic 3D nanonetwork wound dressing with excellent tissue adhesion and biocompatibility is designed by the assembly of pH- and near infrared-responsive CNF nanoskeletons, magnetic switching Fe3O4 nanoparticles, and temperature switching Pluronic®F-127. The dressing with high loading capacity for mitomycin and indocyanine green can form a sticky 3D nanonetwork at the wound site and remain for a long time to release drugs through an external magnetic field. Interestingly, the dressing possessed excellent antibacterial activity, bacterial biofilm elimination, T24 tumour cell killing, and wound healing promotion through photothermal, photodynamic, and chemotherapy. Therefore, it has promising application for bladder postoperative infected wound healing to avoid rapid loss of drugs due to cyclical urination.

Prognostic value of CD8+ tumor-infiltrating T cells in patients with breast cancer: A systematic review and meta-analysis.

CD8+ tumor-infiltrating lymphocytes have been regarded as potential biomarkers for cancer prognosis, while the prognostic effect of CD8+ tumor-infiltrating T cells remains controversial in breast cancer. In the present study, a meta-analysis was performed to evaluate the prognostic value of CD8+ T cells in breast cancer and the associations between CD8+ T cells and the pathological characteristics. The PubMed, Embase and the Cochrane Library were systematically searched entries added from the establishment of the database to November 2021 and prospective or retrospective studies of patients with breast cancer were included. The Newcastle-Ottawa Scale was used to assess the quality of evidence for each study. STATA 15.1 was used for the data analysis. A total of 14 studies comprising 22,222 patients were included in the final analysis and the pooled results suggested that a high CD8+ T-cell infiltration level was significantly related to better overall survival [hazard ratio (HR)=0.70, 95% confidence interval (CI): 0.60-0.82, P<0.001] and disease-free survival (HR=0.63, 95% CI: 0.49-0.81, P<0.001) for patients with breast cancer. In addition, a high CD8+ T-cell infiltration level was significantly associated with decreased expression of estrogen receptor [odds ratio (OR)=1.92, 95% CI: 1.30-2.85, P=0.001] and progesterone receptor (OR=1.66, 95% CI: 1.14-2.42, P=0.008), and increased human epidermal growth factor receptor 2 expression (OR=0.79, 95% CI: 0.66-0.94, P=0.010) in patients with breast cancer, while there was no significant association between CD8+ T-cell infiltration and age, tumor size or lymph node status of patients with breast cancer (P>0.05). In conclusion, CD8+ T-cell infiltration is of prognostic value in patients with breast cancer. High levels of CD8+ T-cell infiltration were related to improved prognosis, including OS and DFS, in patients with breast cancer.

Dual light-responsive cellulose nanofibril-based in situ hydrogel for drug-resistant bacteria infected wound healing.

In situ hydrogels with rapid hemostasis and antibacterial activity have received considerable attention in the field of wound healing. Herein, a white light and NIR dual light-responsive cellulose nanofibril (CNF)-based in situ hydrogel wound dressing is tailored by using white light-responsive CNF and endogenous antibacterial CNF as the skeleton, Prussian blue nanoparticles, Pluronic® F127 and hydroxypropyl methyl cellulose as the NIR, temperature-responsive switch and binder, respectively. The dressing exhibits rapid hemostasis properties in rat liver injury model with low blood loss of 286.4 mg and short hemostasis time of 63 s. Meanwhile, the antibacterial activity of the dressing with white and NIR irradiation against Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) is higher than 99.9 %. Interestingly, the dressing with biocompatibility can promote MRSA infection wound healing and can be removed on demand without secondary injury to skin. Therefore, it has promising applications for first-aid hemostasis and wound healing.

[Effect of electroacupuncture of "Tianshu"(ST25) at different frequencies on electromyography and immunoactivity of SP and VIP of colon in rats with slow transit constipation].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of bilateral "Tianshu"(ST25) at different frequencies on the first black stool discharge time, colonic electromyography (EMG) and immunoactivity of vasoactive intestinal peptide (VIP) and substance P (SP) in the colon tissue in rats with slow transit constipation (STC), so as to choose a better stimulating frequency in the treatment of STC. METHODS: A total of 50 male Wistar rats were randomized into control, model, 2 Hz-EA, 100 Hz- EA, and 2 Hz/100 Hz-EA groups, with 10 rats in each group. The STC model was established by intraperitoneal injection of compound diphenoxylate suspension fluid (10 mg/kg). EA was applied to bilateral ST25 for 30 min, once a day for 14 consecutive days. The discharge time for the first black stool was recorded after gavage of mixed suspension fluid of active carbon (2 mL) for assessing the gastrointestinal motility. The colonic EMG was recorded by using a pair of silver electrodes and bioelectric amplifier. The expression of SP and VIP in the colonic tissue was detected by immunohistochemistry. RESULTS: Following mode-ling, the colonic EMG amplitude, the discharge time for the first black stool and VIP immunoactivity were significantly increased (P<0.01), and the EMG frequency and SP immunoactivity were significantly decreased （P<0.01） in the model group compared with the control group. Compared with the model group, the increase of the discharge time for the first black stool, EMG amplitude and VIP immunoactivity, the decrease of EMG frequency and SP immunoactivity were reversed in the 3 EA groups (P<0.01, P<0.05). The therapeutic effect of 100 Hz-EA was notably weaker than that of both 2 Hz-EA and 2 Hz/100 Hz-EA in up-regulating EMG frequency and SP immunoactivity and in down-regulating the discharge time for the first black stool, EMG amplitude and VIP immunoactivity (P<0.05, P<0.01). There was no significant difference between the 2 Hz/100 Hz-EA and 2 Hz-EA groups (P>0.05). CONCLUSION: EA can accelerate colonic EMG activities, which may be associated with its functions in down-regulating VIP immunoactivity and up-regulating SP immunoactivity in the colonic tissues. The therapeutic effects of 2 Hz/100 Hz-EA and 2 Hz-EA are better than that of 100 Hz-EA.

Tensile behavior of bio-inspired hierarchical suture joint with uniform fractal interlocking design.

Hierarchical interlocking leads to optimal mechanical properties for sutures in nature. Inspired by this, a design method for describing a hierarchal triangular suture joint based on Koch fractal interlocking is developed. The effect of geometrical interlocking was examined by the analysis of the load transmission between joined parts. Samples of hierarchal suture joints were fabricated by using a high-resolution 3D printer and tensile tests were conducted to examine the mechanical behavior of these joints. The surface displacement and strain fields were obtained using the Digital Image Correlation (DIC) technology where the images were taken by a high-resolution microscope camera. Finite element models of the hierarchal suture joints were generated to simulate the tensile responses and to predict the stress distributions and failure modes. The numerical results show good agreement with the experimental data. The results of this study show that the second order suture joint with a sinusoidal center line exhibits not only high strength but also high ductility. Moreover, by increasing the hierarchical order from two to three, the stiffness and strength do not improve while the fracture toughness actually decreases, suggesting that increasing the fractal complexity does not always lead to the improvement of the structure's load-carrying capacity, even with low iterations for the fractal complexity. The results obtained in this study can serve as a guideline to the engineering design of suture joints with fractal interlocks.

Dual PI3K/mTOR inhibitor PKI-402 suppresses the growth of ovarian cancer cells by degradation of Mcl-1 through autophagy.

The phosphoinositide 3-kinase (PI3K) /AKT/mammalian target of rapamycin (mTOR) signaling pathway is frequently mutated in cancers, leading to increased cell proliferation, migration, and chemoresistance. Currently, a number of small molecule inhibitors of the PI3K/AKT/mTOR signaling pathway have been assessed in preclinical and clinical studies. It has been found that dual PI3K/mTOR inhibitors may inhibit cell proliferation and induce apoptosis in cancers, but the mechanism is still being explored. Therefore, determining the role of dual PI3K/mTOR inhibitors PKI-402 in cancer cells may facilitate overcoming chemoresistance. By referring to a gene database and screening gene sequences, we found that human ovarian cancer epithelial cell lines SKOV3 and A2780 had mutations of the PIK3CA gene, which might be relatively sensitive to dual-targeted PI3K/mTOR inhibitors. In this study, our data indicated that dual PI3K/mTOR inhibitor PKI-402 disrupted the balance of Bcl-2 family proteins by degrading the Mcl-1 protein through autophagy. Moreover, the autophagy receptor protein p62 bound to Mcl-1 through its ubiquitin-associated domain (UBA domain) to participate in the degradation of Mcl-1 through autophagy. This offers hope for the treatment of ovarian cancer patients with mutations of the PI3K/AKT/mTOR pathway.

Intelligent Cellulose Nanofibers with Excellent Biocompatibility Enable Sustained Antibacterial and Drug Release via a pH-Responsive Mechanism.

Novel nanosized biomass-based pH-responsive cellulose nanofibers (CNF-PEI) with excellent biocompatibility were tailored by grafting polyethylenimine (PEI) onto carboxylated cellulose nanofibers (CNF-COOH); the active site (-COOH, 0.96 mmol/g) was anchored on cellulose nanofibers (CNFs) to introduce PEI with a high density (10.57 mmol/g) of amino groups. The as-prepared CNF-PEI not only maintained the good properties of CNFs but also possessed excellent biocompatibility and pH-responsive properties, offering interesting possibilities for pH-induced sustained drug release and medical dressing. The CNF-PEI showed rapid wettability conversion from hydrophilic, underwater superoleophobic (WCA = 20.7°, OCA = 159.3°) to hydrophobic, superoleophilic (WCA = 129.6°, OCA = 29.7°) in response to pH change from acidic conditions to alkaline conditions. The antibacterial activity of CNF-PEI toward Escherichia coli and Listeria monocytogenes was 100% and 94.6% under acidic conditions, respectively. Furthermore, the pH-responsive mechanism of CNF-PEI was revealed by XPS, 13C NMR, 1H NMR, and AFM analyses.