Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

Unraveling Pinus massoniana's defense mechanisms against Bursaphelenchus xylophilus under aseptic conditions: A transcriptomic analysis.

Pine wilt disease (PWD) is caused by pine wood nematode (PWN, Bursaphelenchus xylophilus) and significantly impacts pine forest ecosystems globally. This study focuses on Pinus massoniana, an important timber and oleoresin resource in China, and is highly susceptible to PWN. However, the defense mechanism of pine trees in response to PWN remains unclear. Addressing the complexities of PWD, influenced by diverse factors like bacteria, fungi, and environment, we established a reciprocal system between PWN and P. massoniana seedlings under aseptic conditions. Utilizing combined second and third-generation sequencing technologies, we identified 3,718 differentially expressed genes post-PWN infection. Transcript analysis highlighted the activation of defense mechanisms via stilbenes, salicylic acid and jasmonic acid pathways, terpene synthesis, and induction of pathogenesis-related proteins and resistance genes, predominantly at 72 hours post-infection. Notably, terpene synthesis pathways, particularly the mevalonate pathway, were crucial in defense, suggesting their significance in P. massoniana's response to PWN. This comprehensive transcriptome profiling offers insights into P. massoniana's intricate defense strategies against PWN under aseptic conditions laid a foundation for future functional analyses of key resistance genes.

Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

Research Progress of Antioxidants in Oxidative Stress Therapy after Spinal Cord Injury.

Spinal cord injury (SCI) is a serious problem in the central nervous system resulting in high disability and mortality with complex pathophysiological mechanisms. Oxidative stress is one of the main secondary reactions of SCI, and its main pathophysiological marker is the production of excess reactive oxygen species. The overproduction of reactive oxygen species and insufficient antioxidant capacity lead to the occurrence of oxidative stress and neuroinflammation, and the dysregulation of oxidative stress and neuroinflammation leads to further aggravation of damage. Oxidative stress can initiate a variety of inflammatory and apoptotic pathways, and targeted antioxidant therapy can greatly reduce oxidative stress and reduce neuroinflammation, which has a certain positive effect on rehabilitation and prognosis in SCI. This article reviewed the research on different types of antioxidants and related treatments in SCI, focusing on the mechanisms of oxidative stress.

Luminescent Neutral Cyclometalated Iridium(III) Complexes Featuring a Cubic Polyhedral Oligomeric Silsesquioxane for Lipid Droplet Imaging and Photocytotoxic Applications.

New neutral iridium(III) complexes featuring a cubic polyhedral oligomeric silsesquioxane (POSS) unit, [Ir(N∧C)2(L1-POSS)] [HN∧C = 2-phenylpyridine (Hppy; 1), 2-phenylbenzothioazole (Hbt; 2), and 2-(1-naphthyl)benzothiazole (Hbsn; 3); L1-POSS = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-heptakis(isobutyl)POSS-propyl carbamate], were designed and synthesized. Their POSS-free counterparts, [Ir(N∧C)2(L1)] [L1 = (E)-N-(4-hydroxymethylphenyl)-1-(2-hydroxyphenyl)methanimine; HN∧C = Hppy (1a), Hbt (2a), and Hbsn (3a)], and the poly(ethylene glycol) (PEG) derivatives [Ir(N∧C)2(L1-PEG)] [L1-PEG = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-[2-[ω-methoxypoly(1-oxapropyl)]ethyl]carbamate; HN∧C = Hppy (1b), Hbt (2b), and Hbsn (3b)] were also prepared. The photophysical, photochemical, and biological properties of the POSS complexes were compared with those of their POSS-free and PEG-modified counterparts. Upon irradiation, all of these complexes displayed orange-to-red emission and long emission lifetimes under ambient conditions. The bsn complexes 3, 3a, and 3b exhibited the highest singlet oxygen (1O2) generation quantum yields (ΦΔ = 0.85-0.86) in aerated CH3CN. Laser-scanning confocal microscopy images revealed that complexes 1-3 and 1a-3a showed exclusive lipid-droplet staining upon cellular uptake, while the PEG derivatives 1b-3b displayed lysosomal localization. Complex 3 was utilized to study various lipid-droplet-related biological events including lipid-droplet accumulation under oleic acid stimulation, the movement of lipid droplets, and preadipocyte differentiation. Notably, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the ppy complexes 1 and 1b and the bt complexes 2 and 2b were noncytotoxic both in the dark and upon irradiation at 450 nm for 5 min (IC50 > 200 µM), while the bsn complexes 3, 3a, and 3b showed low dark cytotoxicity (IC50 = 52.9 to >200 µM) and high photocytotoxicity (IC50 = 1.1-5.3 µM). The cellular uptake, internalization mechanisms, and cell death pathways of these complexes were also investigated. This work not only offers promising luminescent probes for lipid droplets through the structural modification of iridium(III) complexes but also paves the way to the construction of new reagents for theranostics.

PTEN-silencing combined with ChABC-overexpression in adipose-derived stem cells promotes functional recovery of spinal cord injury in rats.

The efficiency of cell therapy after spinal cord injury (SCI) depend on the survival of transplanted cells. However, sterile microenvironment and glial scar hyperplasia extremely reduce their numbers. Our previous study found overexpression of ChABC gene is positively correlated to migration ability. Expression of PTEN gene is closely associated with proliferation. However, whether manipulation of PTEN and ChABC on adipose-derived mesenchymal stem cells (ADSCs) promote motor recovery is unknown. This study aimed to promote hindlimb function recovery in SCI rats by enhancing proliferation and migration ability of ADSCs, transiently silencing expression of PTEN following overexpression of ChABC (double-gene modified ADSCs, DG-ADSCs). After PTEN silencing, we observed strong proliferation and accelerated G1-S transition in DG-ADSCs using CCK8 assay and flow cytometry. In addition, we demonstrated that migration numbers of DG-ADSCs were higher than control group using Transwell assay. The protein and mRNA levels of MAP2 and ßⅢ-tubulin in DG-ADSCs were increased compared with ADSCs. These results were further confirmed in SCI rats. Increased survival cells and reduction of glial scars were quantitatively analyzed in DG-ADSCs groups, which is definitely correlated to function recovery. Recovery of motor function was observed in DG-ADSCs treatment rats using BBB score, which emphasized that improved viability of transplanted cells and reduction of glial scars were an effective strategy for enhancing recovery of neurological function after SCI.

Luminescent Molecular Octopuses with a Polyhedral Oligomeric Silsesquioxane (POSS) Core and Iridium(III) Polypyridine Arms: Synthesis, Aggregation Induced Emission, Cellular Uptake, and Bioimaging Studies.

A new class of luminescent molecular hybrids in which eight cyclometalated iridium(III) polypyridine complexes are grafted onto a polyhedral oligomeric silsesquioxane (POSS) unit [POSS-{Ir(N^C)2 (py-im)}8 ](PF6 )8 [py-im=pyridine imine; HN^C=N-phenylpyrazole (Hppz) (1 a), 2-phenylpyridine (Hppy) (2 a), 2-phenylquinoline (Hpq) (3 a)] were synthesized and characterized. On photoexcitation, the complexes showed intense and long-lived orange-red to red emission in fluid solutions at room temperature and in low-temperature glasses. The photophysical properties including aggregation-induced emission and biological properties of these complexes were studied and compared with those of their POSS-free counterparts [Ir(N^C)2 (py-im)](PF6 ) [HN^C=Hppz (1 b), Hppy (2 b), Hpq (3 b)]. The (photo)cytotoxicity of the complexes was examined by the MTT assay, and their cellular uptake and intracellular localization were investigated by inductively coupled plasma-mass spectrometry and laser-scanning confocal microscopy.

A rapid and sensitive resonance Rayleigh scattering spectra method for the determination of quinolones in human urine and pharmaceutical preparation.

A new method based on resonance Rayleigh scattering (RRS) was proposed for the determination of quinolones (QNS) at the nanogram level. In pH 3.3-4.4 Britton-Robinson buffer medium, quinolones such as ciprofloxacin, pipemidic acid (PIP), lomefloxacin (LOM), norfloxacin (NOR) and sarafloxacin (SAR) were protonated and reacted with methyl orange (MO) to form an ion-pair complex, which then further formed a six-membered ring chelate with Pd(II). As a result, new RRS spectra appeared and the RRS intensities were enhanced greatly. RRS spectral characteristics of the MO-QNS-Pd(II) systems, the optimum conditions for the reaction, and the influencing factors were investigated. Under optimum conditions, the scattering intensity (∆I) increments were directly proportional to the concentration of QNS with in certain ranges. The method had high sensitivity, and the detection limits (3σ) ranged from 6.8 to 12.6 ng/mL. The proposed method had been successfully applied for the determination of QNS in pharmaceutical formulations and human urine samples. In addition, the mechanism of the reaction system was discussed based on IR, absorption and fluorescence spectral studies. The reasons for the enhancement of scattering spectra were discussed in terms of fluorescence-scattering resonance energy transfer, hydrophobicity and molecular size.

Triple-wavelength overlapping resonance Rayleigh scattering method for facile and rapid assay of perfluorooctane sulfonate.

In the present study, a novel triple-wavelength overlapping resonance Rayleigh scattering (TWO-RRS) method had been well established to detect perfluorooctane sulfonate (PFOS). We found that crystal violet (CV) could react with PFOS to form 1:1 ion-association complex by electrostatic attraction and hydrophobic effect over a wide pH range (5.0∼11.0) in less than 60 s. The complexes would further self-aggregated into nanoparticles [CV-PFOS]n. Based on this phenomenon, not only the absorption and Raman spectra were changed but also the resonance Rayleigh scattering (RRS) intensities were significantly enhanced. And three new RRS peaks located at 327, 492, and 654 nm were clearly observed, respectively. At the same time, it was found that both the enhanced single-wavelength resonance Rayleigh scattering (SW-RRS) and TWO-RRS intensities against the concentration of PFOS showed an excellent correlation. The detection limits for the three single peaks were 27.4 nmol L(-1) (13.7 µg L(-1), 327 nm), 27.5 nmol L(-1) (13.8 µg L(-1), 492 nm), and 31.4 nmol L(-1) (15.7 µg L(-1), 654 nm), and for TWO-RRS method was 5.9 nmol L(-1) (3.0 µg L(-1)). Moreover, it could be applied to determine PFOS water samples successfully.

Development of a highly sensitive chemiluminescence enzyme immunoassay using enhanced luminol as substrate.

In this study, a high sensitivity chemiluminescence enzyme immunoassay (CLEIA) based on novel enhancers was developed. Under optimal conditions, we developed an enhanced chemiluminescence reaction (ECR) catalyzed by horseradish peroxidase (HRP-C) in the presence of 3-(10'-phenothiazinyl) propane-1-sulfonate (SPTZ) and 4-morpholinopyridine (MORP) as enhancers. The limit of detection of the newly prepared chemiluminescent cocktail for HRP was 0.33 pg/well, which is lower than that of commercial Super Signal substrate. The results showed that this novel chemiluminescent cocktail can significantly increase the light output of HRP-catalyzed ECR, which can be translated into a corresponding improvement in sensitivity. Similar improvements were observed in CLEIA for the determination of chloramphenicol in milk. In addition, the ECR of N-azoles as secondary enhancer was also presented.

The influence of different sources of anticipated instrumental support on depressive symptoms in older adults.

Objective: This study investigated how anticipated instrumental support sources and intergenerational support influence depressive symptoms in older Chinese adults. Methods: We employed binary logistic regression on data from 7,117 adults aged ≥60 in the 2018 China Health and Retirement Longitudinal Study, controlling for gender, marital status, and self-rated health. Results: 38.89% of respondents exhibited depressive symptoms. Anticipated support from spouse and children, spouse only, children only, or other sources showed 52, 25, 46, and 40% lower odds of depression, respectively, compared with no anticipated support. Those providing financial support had 36% higher odds of depression than those without exchanges. However, those receiving financial support, receiving instrumental support, and receiving and providing financial and emotional support had 19, 14, 23, and 24% lower odds of depression. Conclusion: Different anticipated instrumental support sources and intergenerational support influenced depression odds in older adults, suggesting potential benefits in promoting such support systems.

Mechanisms of oral microflora in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease with complex pathogenesis and no effective treatment. Recent studies have shown that dysbiosis of the oral microflora is closely related to the development of PD. The abnormally distributed oral microflora of PD patients cause degenerative damage and necrosis of dopamine neurons by releasing their own components and metabolites, intervening in the oral-gut-brain axis, crossing the biofilm, inducing iron dysregulation, activating inter-microflora interactions, and through the mediation of saliva,ultimately influencing the development of the disease. This article reviews the structure of oral microflora in patients with PD, the mechanism of development of PD caused by oral microflora, and the potential value of targeting oral microflora in developing a new strategy for PD prevention, diagnosis and treatment.

Effects of multimorbidity coexistence on the risk of mortality in the older adult population in China.

Background: Multimorbidity coexistence is a serious public health issue affecting a significant number of older adults worldwide. However, associations between multimorbidity and mortality are rarely studied in China. We assessed the effects of multimorbidity coexistence on mortality among a nationwide sample of older adults from China. Objective: We analyzed 10-year (2008-2018) longitudinal data of 12,337 individuals who took part in China, a nationwide survey of people aged 65 years and above. We used the Cox proportional hazard model to determine the effects of multimorbidity on the all-cause mortality risk. We also examined mortality risk between sex and age obtained through differential analysis. Results: At baseline, 30.2, 29.9, and 39.9% of participants had 0, 1, and 2 or more diseases, respectively. The cumulative follow-up of this study was 27,428 person-years (median follow-up = 2.7 years; range, 0.01-11.3 years), with 8297 deaths. The HRs (95% CIs) for all-cause mortality in participants with 1, and 2 or more conditions compared with those with none were 1.04 (0.98, 1.10) and 1.12 (1.06, 1.18), respectively. The heterogeneity analysis indicated that, the mortality risk for 80-94 years and 95-104 years group with multimorbidity coexistence is 1.12 (1.05-1.21) and 1.11 (1.01-1.23), respectively, but the mortality risk for 65-79 years group with multimorbidity coexistence was not statistically significant. The heterogeneity analysis indicated that, the mortality risk for men and women in older adults with multimorbidity coexistence is 1.15 (1.06, 1.25) and 1.08 (1.01, 1.17), respectively. Conclusion: Multimorbidity coexistence is associated with an increase in an increased risk of death in older individuals, with the effect being relatively significant in those aged 80-94 years.

Exosomes Secreted by Hypoxia-Pre-conditioned Adipose-Derived Mesenchymal Stem Cells Reduce Neuronal Apoptosis in Rats with Spinal Cord Injury.

Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.

Effect of intergenerational exchange patterns and intergenerational relationship quality on depressive symptoms in the elderly: An empirical study on CHARLS data.

Background: As the population ages with fewer children, depression symptoms are increasing among the elderly who lack companionship. Intergenerational support is closely related to depression in the elderly; hence how the behavioral patterns and emotional quality of intergenerational support affect depressive symptoms in the elderly should be further explored. Objective: To study the effects of intergenerational exchange patterns and intergenerational relationship quality on depressive symptoms in the elderly. Methods: A total of 8,015 people over 60 years old in CHARLS in 2018 were selected as the object of this study. First, the correlation between demographics, economic conditions, health status, intergenerational support patterns, intergenerational relationship quality, and depressive symptoms in the elderly were analyzed. Three regression analysis models were established to analyze the relationship between control variables, intergenerational support patterns, intergenerational relationship quality, and depressive symptoms in the elderly. Results: Among the intergenerational economic, care, and emotional exchange modes, the risk of depressive symptoms in the elderly in the mutual support group was 31.8, 38.4, and 25.5% lower than that in the non-communication group. Compared with the elderly with very poor intergenerational relationship quality, the elderly with good, very good, and excellent intergenerational relationship quality had 74.5, 84.0, and 85.6% lower risk of depressive symptoms. Discussion: Different cultural backgrounds also affect intergenerational exchange patterns and depression in the elderly. During the study of depressive symptoms, two aspects relating to intergenerational support should be considered behaviorally and emotionally: the intergenerational exchange model and the intergenerational relationship quality. As depression in the elderly is affected by multiple factors, the participation and joint efforts of the whole society are required to reduce depressive symptoms in the elderly and realize active aging. Conclusion: The intergenerational exchange pattern of mutual support and the higher quality of the intergenerational relationship can significantly reduce the depressive symptoms of the elderly.

Tenosynovial giant cell tumor involving the cervical spine: A case report.

BACKGROUND: Tenosynovial giant cell tumors (TGCTs) are a frequent benign proliferative disease originating from the synovial membrane. However, TGCTs rarely occur in the spine. The purpose of this paper is to report a case of TGCT occurring in the cervical spine. Although the disease is rare, it is essential to consider the possibility of TGCT in axial skeletal lesions. Awareness of spinal TGCTs is important because their characteristics are similar to common spinal tumor lesions. CASE SUMMARY: A 49-year-old man with a 2-year history of neck pain and weakness in both lower extremities was referred to our ward. Imaging revealed a mass extending from the left epidural space to the C4-5 paravertebral muscles with uneven enhancement. The tumor originated in the synovium of the C4-5 lesser joint and eroded mainly the C4-5 vertebral arch and spine. Puncture biopsy was suggestive of a giant cell-rich lesion. The patient had pulmonary tuberculosis, and we first administered anti-tuberculosis treatment. After the preoperative requirements of the anti-tuberculosis treatment were met, we used a posterior cervical approach to completely remove the mass after fixation with eight pedicle screws. The mass was identified as a TGCT by postoperative immunohistochemical analysis. Recurrence was not detected after 1 year of follow-up. CONCLUSION: Spinal TGCTs are often misdiagnosed. The radiological changes are not specific. The ideal treatment comprises complete excision with proper internal fixation, which can significantly reduce postoperative recurrence.

Tuning the organelle specificity and cytotoxicity of iridium(III) photosensitisers for enhanced phototheranostic applications.

Luminescent cyclometallated iridium(III) complexes with a polyhedral oligomeric silsesquioxane (POSS) unit were designed as efficient theranostic agents that displayed tuneable organelle-targeting properties, minimal dark cytotoxicity and substantial photocytotoxicity even under hypoxic conditions.

Dendrite-Free Lithium Anodes Enabled by a Commonly Used Copper Antirusting Agent.

Li metal is considered the most promising anode for high energy density secondary batteries due to its high theoretical capacity and low redox potential. However, lithium is prone to form dendrites which will not only cause internal short-circuits but also bring accumulation of "dead Li" and result in fast capacity decay, thus its large-scale application is challenging. In this work, we demonstrate that the commonly used metal corrosion inhibitor, benzotriazole (BTA), can be used to modify the Cu foil surface and guide homogeneous Li+ plating/stripping due to the lithiophilic nature of the N atom in the BTA molecule. As a result, the lithium plated on the BTA modified Cu (BTA-Cu) substrate is free of dendrites, and a Coulombic efficiency (CE) as high as 99.0% was achieved for Li+ plating/stripping on the BTA-Cu substrate at a current density of 1 mA/cm2. Furthermore, the BTA-Cu foil can be used as an anode to assemble an anode-free cell (BTA-Cu∥LFP), and ∼73.3% of the initial capacity can be obtained after 50 cycles. Last but not the least, a BTA-Cu@Li electrode prepared by plating of Li+ on the BTA-Cu substrate can serve as a stable Li anode in a BTA-Cu@Li∥LFP cell and display an average cycled CE of 98.5% at a depth of discharge (DOD) of 33%. This simple method of Li+ plating/stripping behavior regulation could inspire researchers on the development of highly stable lithium metal anodes for high energy density batteries.

Resonance Rayleigh scattering technique for simple and sensitive analysis of tannic acid with carbon dots.

Carbon dots (CDs) are raising a substantial amount of attention owing to their many unique and novel physicochemical properties. Herein one-pot synthesized CDs, to the best of our knowledge, were first served as the robust nanoprobe for detection tannic acid (TA) based on resonance Rayleigh scattering technique. The as-prepared CDs can combine with TA via hydrogen bond, resulting in remarkable enhancement of scattering signal with no changes in the fluorescence of CDs. Therefore, a novel protocol for TA determination was established and this strategy allowed quantitative detection of TA in the linear range of 0.2-10.0µmolL-1 with an excellent detection limit of 9.0nmolL-1. Moreover, the CDs based nanoprobe can be applied to the determination of TA in water sample with satisfactory results. Our study can potentially influence our current views on CDs and particularly impressive and offers new insights into application of CDs beyond the traditional understanding of CDs.

Determination of sunset yellow in soft drinks based on fluorescence quenching of carbon dots.

Fluorescent carbon dots was prepared by heating N-(2-hydroxyethyl)ethylene diaminetriacetic acid in air. The carbon dots were not only highly soluble in water but also uniform in size, and possessed strong blue fluorescence and excitation wavelength-dependent emission properties with the maximum excitation and emission wavelength at 366nm and 423nm, respectively. Food colorant sunset yellow whose excitation and emission wavelength at 303nm and 430nm could selectively quench the fluorescence of carbon dots, efficient fluorescent resonance energy transfer between the carbon dots and sunset yellow is achieved. This was exploited to design a method for the determination of sunset yellow in the concentration range from 0.3 to 8.0µmolL(-1), with a limit of detection (3σ/k) of 79.6nmolL(-1). Furthermore the fluorimetric detection method was established and validated for sunset yellow in soft drinks samples with satisfactory results.