Fluorine Doping Mediated Epitaxial Growth of NaREF4 on TiO2 for Boosting NIR Light Utilization in Bioimaging and Photodynamic Therapy.

By integrating TiO2 with rare earth upconversion nanocrystals (NaREF4), efficient energy transfer can be achieved between the two subunits under near-infrared (NIR) excitation, which hold tremendous potential in the fields of photocatalysis, photodynamic therapy (PDT), etc. However, in the previous studies, the combination of TiO2 with NaREF4 is a non-epitaxial random blending mode, resulting in a diminished energy transfer efficiency between the NaREF4 and TiO2. Herein, we present a fluorine doping-mediated epitaxial growth strategy for the synthesis of TiO2-NaREF4 heteronanocrystals (HNCs). Due to the epitaxial growth connection, NaREF4 can transfer energy through phonon-assisted pathway to TiO2, which is more efficient than the traditional indirect secondary photon excitation. Additionally, F doping brings oxygen vacancies in the TiO2 subunit, which further introduces new impurity energy levels in the intrinsic band gap of TiO2 subunit, and facilitates the energy transfer through phonon-assisted method from NaREF4 to TiO2. As a proof of concept, TiO2-NaGdF4 : Yb,Tm@NaYF4@NaGdF4 : Nd@NaYF4 HNCs were rationally constructed. Taking advantage of the dual-model up- and downconversion luminescence of the delicately designed multi-shell structured NaREF4 subunit, highly efficient photo-response capability of the F-doped TiO2 subunit and the efficient phonon-assisted energy transfer between them, the prepared HNCs provide a distinctive nanoplatform for bioimaging-guided NIR-triggered PDT.

[Comparative study of total knee arthroplasty assisted by robot and remote sensing navigation system].

OBJECTIVE: To compare clinical efficacy of robot-assisted (RA) and remote sensing navigation alignment (RSNA) system-assisted total knee arthroplasty (TKA). METHODS: From March 2023 to June 2023, 60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis (KOA) were admitted and divided into RSNA group and RA group according to different treatment methods, with 30 patients in each group. There were 5 males and 25 females in RSNA group, aged from 56 to 81 years old with an average of(66.33±7.16) years old;body mass index(BMI) ranged from 19.87 to 38.54 kg·m-2 with an average of (28.40±6.18) kg·m-2;the courses of disease ranged from 5 to 36 months with an average of (18.20±8.98) months; RSNA system was used to assist the positioning of osteotomy. There were 7 males and 23 females in RA group, aged from 55 to 82 years old with an average of (67.83±8.61) years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an average of (28.01±4.89) kg·m-2; the courses of disease ranged from 3 to 33 months with an average of (17.93±9.20) months;RA was performed. Operation time, incision length, latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups. Hip-knee ankle angle (HKAA), HKAA deviation, lateral distal femoral angle ( LDFA), medial proximal tibial angle (MPTA) and posterior tibial slope (PTS) were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society score (KSS) were used to evaluate functional recovery before operation, 3 and 6 months after operation. RESULTS: The operation was performed successfully in both groups, and there were no serious complications such as vascular and nerve injury during operation. The wound healed well at stageⅠafter operation, and the follow-up time was 6 months. The operation time, latent blood loss at 2 weeks after operation and incision length in RSNA group were (94.35±5.75) min, (130.54±17.53) ml and (14.73±2.14) cm, respectively;while (102.57±6.88) min, (146.33±19.47) ml and (16.78±2.32) cm in RA group, respectively. RSNA group was better than RA group (P<0.05). No deep vein thrombosis occurred in both groups at 2 weeks after operation, 5 patients occurred intermuscular vein thrombosisin in RSNA group and 8 patients in RA group, the difference was not statistically significant (P>0.05). In RSNA group, HKAA, LDFA and MPTA were (173.00±5.54) °, (86.96±3.45) °, (82.79±3.35) ° before operation, and (178.34±1.85) °, (89.92±0.42) °, (89.84±0.73) ° at 1 week after operation, respectively. In RA group, HKAA, LDFA and MPTA were (173.31±6.48) °, (87.15±3.40) ° and (82.99±3.05) ° before operation, and (178.52±1.79) °, (90.03±0.39) ° and (90.15±0.47) ° at 1 week after operation, respectively. HKAA, LDFA and MPTA were significantly improved in both groups at 1 week after operation (P<0.05). There were no significant difference in HKAA, LDFA, MPTA and PTS between two groups before operation and 1 week after operation (P>0.05). There was no significant difference in deviation distribution of HKAA at 1 week after operation (χ2=2.611, P=0.456). There were no significant difference in WOMAC and KSS between two groups before operation, 3 and 6 months after operation (P>0.05), and postoperative WOMAC and KSS at 3 and 6 months between two groups were improved compared with those before operation (P<0.05). CONCLUSION: Both RA and RSNA system assisted TKA could obtain accurate osteotomy, RA has higher surgical accuracy, RSNA system assisted operation has less trauma, and operation is simpler.

[Application of remote sensing navigation system in total knee arthroplasty].

OBJECTIVE: To explore clinical accuracy of remote sensing navigation alignment (RSNA) system in total knee arthroplasty (TKA) and its influence on postoperative clinical efficacy. METHODS: From May 2021 to May 2022, 60 knee osteoarthritis (KOA) patients with Kellgren-Lawrence (K-L) grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods, and 30 patients in each group. There were 6 males and 24 females in RSNA group, aged from 55 to 86 years old with an average of (68.06±8.23) years old;body mass index (BMI) ranged from 22.15 to 34.58 kg·m-2 with an average of (28.20±3.01) kg·m-2;the courses of disease ranged from 2 to 60 months with an average of (18.80±14.80) months;13 patients with grade Ⅲ and 17 patients with grade Ⅳ according to K-L grading. In traditional operation group, there were 8 males and 22 females, aged from 57 to 85 years old with an average of (67.26±6.32) years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of (27.49±2.32) kg·m-2;the courses of disease ranged from 3 to 60 months with an average of (21.30±16.44) months;14 patients with grade Ⅲ and 16 patients with grade Ⅳ according to K-L grading. Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Knee Society score(KSS) were used to evaluate functional recovery of patients. Hip-knee-ankle angle (HKAA), distal femoral valgus angle (FVA) and distal fermoral flexion angle (DFFA) were measured before operation. HKAA and HKAA deviation angle were measured at 1 week after operation, and defective rate of lower limb force line, femur prosthesis valgus angle (FPVA) and femoral prosthesis flexion angle (FPFA), respectively, were calculated. RESULTS: There were no serious complications such as vascular and nerve injury during operation, and wound healed at stage Ⅰ. Both groups were followed up for 6 months. There were no significant difference in WOMAC index, KSS, HKAA, FVA and DFFA between two groups before operation (P>0.05). The force line defect rate, HKAA, HKAA deviation angle, FPVA deviation angle and FPFA of RSNA group were 6.7%, (178.74±1.56) °, (1.25±1.56) °, (1.84±0.16) ° and (4.85±2.46) °, respectively;while in traditional operation group were 20%, (176.73±3.46) °, (3.27±3.46) °, (2.44±0.26) °, (6.60±1.86) °;the difference between two groups were statistically significant (P<0.05). There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation (P>0.05). CONCLUSION: RSNA system could reduce defective rate of lower limb force line, FPVA deviation angle and FPFA after TKA, which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Correction: Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy.

Correction for 'Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy' by Tingting Wang et al., Chem. Commun., 2024, https://doi.org/10.1039/d4cc03281k.

Radiopharmaceutical-activated silicon naphthalocyanine nanoparticles towards tumor photodynamic therapy.

Naphthalocyanine-based agents exhibit huge potential in photodynamic therapy, yet their photodynamic performance is restricted by the penetration depth of the external laser. Herein, we employed 18F-FDG as an internal light source to excite silicon naphthalocyanine nanoparticles to simultaneously circumvent radiative transition and boost 1O2 generation for tumor suppression.

Highly Efficient Multicolor-Emitting Tetraphenylethylene-Based Organic Salts with Commercialization Prospects.

Since the discovery of aggregation-induced emission from tetraphenylethylene derivatives, various methods have been explored to prepare highly efficient multicolored luminescent materials. Herein, we report a simple and efficient strategy for constructing luminescent organic salts of the tetracationic luminogen, tetrapyridinium-tetraphenylethylene (T4Py-TPE4+), combined with seven di- and tetra-anionic aromatic sulfonate ligands. When aqueous solutions of the cationic luminogen and the anionic ligands were mixed, they rapidly aggregated into organic salts within seconds to minutes, giving yields of up to >90%. This was accompanied by an increase in the emission efficiency from ∼58% to almost 100%, and the ability to tune the emission color between 511 and 586 nm. These improvements were mainly attributed to the strong electrostatic attractions between the cation and anions, which resulted in the formation of a rigid hydrophobic network of the T4Py-TPE4+ luminogen with various π-conjugation lengths. Because these compounds are commercially available, this method opens the possibility of fabricating novel light-emitting materials for device fabrication and research.

Efficient and Stable NIR-II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single-Cell Tracking and Time-Resolved Imaging.

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 µs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93 %) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

Role of intracranial bone marrow mesenchymal stem cells in stroke recovery: A focus on post-stroke inflammation and mitochondrial transfer.

Stem cell therapy has become a hot research topic in the medical field in recent years, with enormous potential for treating a variety of diseases. In particular, bone marrow mesenchymal stem cells (BMSCs) have wide-ranging applications in the treatment of ischemic stroke, autoimmune diseases, tissue repair, and difficult-to-treat diseases. BMSCs can differentiate into multiple cell types and exhibit strong immunomodulatory properties. Although BMSCs can regulate the inflammatory response activated after stroke, the mechanism by which BMSCs regulate inflammation remains unclear and requires further study. Recently, stem cell therapy has emerged as a potentially effective approach for enhancing the recovery process following an ischemic stroke. For example, by regulating post-stroke inflammation and by transferring mitochondria to exert therapeutic effects. Therefore, this article reviews the therapeutic effects of intracranial BMSCs in regulating post-stroke inflammation and mitochondrial transfer in the treatment of stroke, providing a basis for further research.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

NIR-II imaging-guided precise photodynamic therapy for augmenting tumor-starvation therapy by glucose metabolism reprogramming interference.

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy-D-glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000-1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system.

A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H2O2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H2O2 into O2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients.

Application of organoids in basic research and clinical translation of cancers / 天津医药

Organoids are the three-dimensional culture of adult stem cells or pluripotent stem cells in vitro to form tissue analogs with specific structures,which have highly similar tissue properties and physiological functions to the corresponding organs.The emergence of organoid technology has laid an important foundation for research in organ development,disease modeling and drug discovery.Tumor organoid,as an important branch of organoids,is a transition between cell lines and animal models,which can well retain the histological and mutational characteristics of tumors in patients and play an essential role in building tumor organoid sample libraries,reconstructing tumor microenvironment,studying the tumor development mechanism as well as formulating personalized treatment plans and drug screening.Tumor organoids help clinicians to realize precise treatment for patients.However,some factors still limit the further development of tumor organoids,such as the lack of microenvironmental components,vascular structure,high culture cost and technical difficulties.In this review,we summarize the applications and challenges of organoid technology in basic tumor research and clinical translation and look forward to the future development of tumor organoids.

Application of core-shell structured nanofibers in oral tissue regeneration / 中国组织工程研究

BACKGROUND:The combination of good biomechanical properties,controlled drug release and multi-functionality of core-shell structured nanofibers is receiving more and more attention,which also makes them promising for a wide range of applications in the field of oral tissue regeneration. OBJECTIVE:To summarize the preparation,drug loading and release mechanisms of core-shell structured nanofibers and their application in the regenerative repair of oral tissues. METHODS:A computer search of the literature collected in CNKI and PubMed from January 2000 to November 2022 was applied,and the search terms in English and Chinese were"electrospinning,core-shell structures,drug delivery systems,jaw bone regeneration,cartilage regeneration,periodontal tissue regeneration". RESULTS AND CONCLUSION:(1)There are various methods for the preparation of core-shell structured nanofibers,but the coaxial and emulsion methods of electrostatic spinning have unique advantages such as simple operation,diverse material selection and good biocompatibility.(2)Core-shell structured nanofibers can be used as bacteriostatic agents,carriers of different types of drugs,and scaffolds for cell adhesion,providing new therapeutic options for oral tissue regeneration.(3)Controlled degradation and drug release rate of core-shell structured nanofibers can better adapt to the healing process of oral tissue defect repair and achieve ideal tissue regeneration.

Mitochondrial Transplantation and Immune Response of Human Bone Marrow Mesenchymal Stem Cells for the Therapeutic of Ischemic Stroke.

Ischemic stroke is the leading cause of death and disability worldwide, with increasing incidence and mortality, imposing a significant social and economic burden on patients and their families. However, cerebral vascular occlusion leads to acute loss of neurons and destruction of synaptic structures. The limited treatment options cannot adequately address intra-neuronal mitochondrial dysfunction due to stroke. Therefore, stem cell-derived mitochondria transplantation plays an important role in neuronal protection and recovery after stroke, when combined with the intracranial and extracranial immunoregulatory effects of stem cell therapy, revealing the mechanism of transferred mitochondria in stem cells in protecting neurological function among chronic-phase ischemic stroke by affecting the endogenous apoptotic pathway of neuronal cells. This research elaborated on the mitochondrial dysfunction in neurons after ischemic stroke, followed by human bone marrow mesenchymal stem cells (hBMSC) rescued damaged neurons by mitochondrial transfer through tunneling nanotubes (TNTs), and the immunomodulatory effect of the preferential transfer of stem cells to the spleen when transplanted into the body.which created an immune environment for nerve repair, as well as improved neurological recovery after the chronic phase of stroke. This review is expected to provide a novel idea for applying intracranial stem cell transplantation in chronic-phase ischemic stroke treatment.

An Extended NIR-II Superior Imaging Window from 1500 to 1900†nm for High-Resolution In Vivo Multiplexed Imaging Based on Lanthanide Nanocrystals.

High-resolution in vivo optical multiplexing in second near-infrared window (NIR-II, 1000-1700 nm) is vital to biomedical research. Presently, limited by bio-tissue scattering, only luminescent probes located at NIR-IIb (1500-1700 nm) window can provide high-resolution in vivo multiplexed imaging. However, the number of available luminescent probes in this narrow NIR-IIb region is limited, which hampers the available multiplexed channels of in vivo imaging. To overcome the above challenges, through theoretical simulation we expanded the conventional NIR-IIb window to NIR-II long-wavelength (NIR-II-L, 1500-1900 nm) window on the basis of photon-scattering and water-absorption. We developed a series of novel lanthanide luminescent nanoprobes with emission wavelengths from 1852 nm to 2842 nm. NIR-II-L nanoprobes enabled high-resolution in vivo dynamic multiplexed imaging on blood vessels and intestines, and provided multi-channels imaging on lymph tubes, tumors and intestines. The proposed NIR-II-L probes without mutual interference are powerful tools for high-contrast in vivo multiplexed detection, which holds promise for revealing physiological process in living body.

Breeding of ZhongKeFaZaoGeng1 by molecular design.

Double-cropping early-season rice is one important part of staple crop rice. In recent years, great progress has been made in breeding the double-cropping early-season japonica rice variety, ZhongKeFaZaoGeng1 (ZKFZG1), with high yield, good quality, and high resistance. The breeding of ZKFZG1 aimed at the severe problems of low quality, low income and pre-harvest sprouting in double-cropping early-season rice production, and was achieved through molecular design by selecting three parents with different beneficial genes, KongYu131, NanFangChangLiGeng, and JiGeng88 and screening for key agronomic genes in cross-breeding. ZKFZG1 has a compact plant architecture, a plant height of ~90 cm, a number of ~120 grains per panicle, a setting rate of ~85%, a 1000-grain weight of 26 grams, a yield of 8.25 t/ha, and especially good grain quality. The successful breeding of ZKFZG1 provides a new direction for double-cropping early-season rice production.

Preparation of eicosavalent triazolylsialoside-conjugated human serum albumin as a dual hemagglutinin/neuraminidase inhibitor and virion adsorbent for the prevention of influenza infection.

A triazolylsialoside-human serum albumin conjugate was prepared as a multivalent hemagglutinin and neuraminidase inhibitor using a di-(N-succinimidyl) adipate strategy. Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (MALDI-TOF-MS) indicated that five tetravalent sialyl galactosides were grafted onto the protein backbone resulting in an eicosavalent triazolylsialoside-protein complex. Compared with monomeric sialic acid, molecular interaction studies showed that the synthetic pseudo-glycoprotein bound tightly not only to hemagglutinin (HA)/neuraminidase (NA) but also to mutated drug-resistant NA on the surface of the influenza virus with a dissociation constant (KD) in the 1 µM range, attributed to the cluster effect. Moreover, this glycoconjugate exhibited potent antiviral activity against a broad spectrum of virus strains and showed no cytotoxicity towards Human Umbilical Vein Endothelial Cells (HUVECs) and Madin-Darby canine kidney (MDCK) cells at high concentrations. Further mechanistic studies demonstrated this multivalent sialyl conjugate showed strong capture and trapping of influenza virions, thus disrupting the ability of the influenza virus to infect host cells. This research lays the experimental foundation for the development of new antiviral agents based on multivalent sialic acid-protein conjugates.

Effects of short-term extreme temperature treatment on the development and reproductive capacity of Encarsia formosa.

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.