Comparative transcriptomics reveals the mechanism of antibacterial activity of fruit-derived dihydrochalcone flavonoids against Porphyromonas gingivalis.

Porphyromonas gingivalis causes various health issues through oral infections. This study investigates the antibacterial activities of food-derived dihydrochalcone flavonoids against Porphyromonas gingivalis and their mechanisms of antibacterial action through comparative transcriptome profiling. Susceptibility tests showed that two typical dihydrochalcone flavonoids (phloretin and phlorizin) had much lower minimum inhibitory concentrations (12.5 µg mL-1 and 50 µg mL-1, respectively) than the common flavanone naringenin (100 µg mL-1). SEM observations and the LDH activity assay indicated obvious anomalies in cell morphology and increased cell membrane permeability, indicating the destructive effect of those compounds on the cell structure. These compounds might also induce apoptosis in P. gingivalis, as shown by the CLSM fluorescence images. Transcriptomic analysis revealed that the flavonoid treatment impacted DNA function and oxidative damage. These flavonoids may activate antioxidant-related pathways that are lethal to anaerobic bacteria like P. gingivalis. Additionally, the compounds resulted in the silencing of transposition-related genes, potentially inhibiting resistance-gene acquisition and expression. Phloretin regulated fatty acid metabolism pathways, which are related to the construction and maintenance of the cell membrane. This suggests a relationship between the structure and antibacterial activities of the tested compounds that share a flavonoid skeleton but differ in the C-ring and glucose moiety. This is the first report of the antibacterial activities and mechanisms of action of food-derived dihydrochalcone flavonoids at the transcriptome level, offering a promising approach for the development of new antibacterial agents from natural products and enhancing their applicability in treating diseases associated with oral pathogens as a substitute for antibiotics.

The Anti-Biofilm Properties of Phloretin and Its Analogs against Porphyromonas gingivalis and Its Complex Flora.

Porphyromonas gingivalis is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure P. gingivalis and the flora of P. gingivalis mixed with the symbiotic oral pathogens Fusobacterium nucleatum and Streptococcus mitis. The results showed that the tested flavonoids had little effect on the biofilm amount of pure P. gingivalis, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on P. gingivalis and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against P. gingivalis and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure-activity relationships.

Efficient regioselective enzymatic acylation of troxerutin: difference characterization of in vitro cellular uptake and cytotoxicity.

In this study, we developed a multi-site acylation strategy to improve the lipophilicity and cellular uptake of troxerutin, a natural flavonoid with many health-promoting bioactivities. By clarifying the acylation properties of troxerutin catalyzed by lipases from different sources, a series of troxerutin ester derivatives acylated at different sites was synthesized, including troxerutin dipropyl (TDP), tripropyl (TTP), tetrapropyl (TEP), dibutyl (TDB), monohexyl (TMH), monooctyl (TMO) and monodecyl (TMD) esters. Interestingly, the troxerutin esters acylated at multiple sites with shorter fatty chains (TDP, TTP and TEP) had similar lipophilicity to the mono-acylated esters bearing longer fatty chains (TMH, TMO and TMD, respectively) and meanwhile demonstrated surprisingly lower cytotoxicity than that of the long fatty-chain mono-esters. In particular, the multi-acylated esters with shorter fatty chains showed remarkably higher cellular uptake than the mono-esters with long fatty chains. In vitro gastrointestinal digestion suggested that the multi-acylated esters of troxerutin were more resistant to gastrointestinal degradation than the mono-esters. These results indicated that multi-site acylation with short fatty chains could be an effective alternative to introducing one-site mono-acylation for the modification of troxerutin and other flavonoid compounds.

The Effect of Conjunctival Flap Transplantation, Pterygium Excision, and Scleral Fixation Surgery in Treating Pterygium Combined with Conjunctival Laxity and Its Impact on Postoperative Complications.

Objective: Pterygium and conjunctival laxity are common ocular conditions that can significantly affect visual comfort and quality of life. Therefore, it is essential to investigate ways to treat these problems. This study aimed to compare the effectiveness of same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery versus staged pterygium excision, crescentic conjunctiva excision, and scleral fixation surgery in treating pterygium combined with conjunctival laxity. The study also aimed to evaluate the impact of these surgical techniques on postoperative complications. Methods: From June 2019 to May 2021, 90 patients (90 eyes) with pterygium combined with conjunctival laxity were included in this study and were randomly divided into two groups (A and B) using a simple number table method. Group A underwent same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery, while group B underwent staged pterygium excision, crescentic conjunctiva excision, and scleral fixation surgery. The International Ocular Surface Disease Index (OSDI), degree of conjunctival laxity excision, changes in ocular tear film dynamics, recurrence rate, and postoperative complications were compared between the two groups. Results: The results showed that different surgical methods for pterygium and conjunctivochalasis did not significantly improve the symptoms and quality of life of patients. This suggests that more intensive research is needed to find more effective treatments. Therefore, the risks and benefits should be carefully considered when selecting ophthalmologic surgery, OSDI scores and fluorescein staining results of both groups were trending downward after surgery, while the breakup time of the tear film and height of the tear meniscus was increasing but there was no significant difference in the above indicators (P > .05). However, there was no significant difference in the above indicators between the two groups before surgery, at 1, 3, and 6 months, and at 1 year after surgery (P > .05). There was also no significant difference in the degree of conjunctival laxity excision between the two groups at 1 and 3 months after surgery (P > .05). Finally, there was no significant difference in the healing time of the conjunctiva and recurrence rates between the two groups (P > .05). The results showed that different surgical methods for pterygium and conjunctivochalasis did not significantly improve the symptoms and quality of life of patients. This suggests that more intensive research is needed to find more effective treatments. Therefore, the risks and benefits should be carefully considered when selecting ophthalmologic surgery. Conclusion: The results of this study showed no significant differences between surgical techniques, making monitoring and management of complications after surgery even more critical. Patients need to be carefully watched for possible complications such as infection, discomfort, and inflammation. Doctors and medical teams should be alert in advance and take appropriate measures to deal with these problems in a timely manner to ensure the success of the operation and the comfort of the patient. By monitoring and proactively managing potential complications, unnecessary pain and complexity can be reduced, thereby improving patient experience and outcomes. Additionally, the study had several limitations, including a small sample size, a limited study period, and failure to consider other potential factors. These limitations need to be addressed in future studies to validate and extend the results of this study. In conclusion, same-stage trapezoidal conjunctival flap transplantation, pterygium excision, and scleral fixation surgery is an effective treatment for patients with pterygium combined with conjunctival laxity, which can improve their visual function and ocular tear film dynamics. However, careful monitoring and management of postoperative complications are necessary.

Highly efficient whole-cell biosynthesis and cytotoxicity of esculin esters.

Esculin is a polyphenol with multiple bioactivities and poor lipophilicity. Therefore, a whole-cell catalytic strategy for esculin acylation was developed to improve its lipophilicity. A total of 12 strains were tested, among which Pseudomonas stutzeri exhibited the highest catalytic activity and mono-acylated regioselectivity. The conversion reached the highest level of 92.7 % at 24 h under the optimal conditions, when vinyl acetate was used as an acyl donor. The catalytic ability of P. stutzeri remained above 60 % after three cycles. Subsequently, five esculin esters with different lengths of fatty chains were synthesized and structurally identified. Of them, esculin-6'-O-octanoate, esculin-6'-O-laurate, and esculin-6'-O-myristate exhibited cytotoxicity on LO2 cells by inducing apoptosis and necrosis. The cytotoxicity of these three esters may attribute to their membrane-disrupting properties. This study provides a novel whole-cell biocatalytic strategy for the acylation of esculin and insight for application of esculin esters as a food additive or drug.

Perceptual span is independent of font size for older and young readers: Evidence from Chinese.

Research suggests that visual acuity plays a more important role in parafoveal processing in Chinese reading than in spaced alphabetic languages, such that in Chinese, as the font size increases, the size of the perceptual span decreases. The lack of spaces and the complexity of written Chinese may make characters in eccentric positions particularly hard to process. Older adults generally have poorer visual capabilities than young adults, particularly in parafoveal vision, and so may find large characters in the parafovea particularly hard to process compared with smaller characters because of their greater eccentricity. Therefore, the effect of font size on the perceptual span may be larger for older readers. Crucially, this possibility has not previously been investigated; however, this may represent a unique source of age-related reading difficulty in logographic languages. Accordingly, to explore the relationship between font size and parafoveal processing for both older and young adult readers, we manipulated font size and the amount of parafoveal information available with different masking stimuli in 2 silent-reading experiments. The results show that decreasing the font size disrupted reading behavior more for older readers, such that reading times were longer for smaller characters, but crucially, the influence of font size on the perceptual span was absent for both age groups. These findings provide new insight into age-related reading difficulty in Chinese by revealing that older adults can successfully process substantial parafoveal information across a range of font sizes. This indicates that older adults' parafoveal processing may be more robust than previously considered. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Flexible parafoveal encoding of character order supports word predictability effects in Chinese reading: Evidence from eye movements.

Several eye-movement studies have revealed flexibility in the parafoveal processing of character-order information in Chinese reading. In particular, studies show that processing a two-character word in a sentence benefits more from parafoveal preview of a nonword created by transposing rather than replacing its two characters. One issue that has not been investigated is whether the contextual predictability of the target word influences this processing of character order information. However, such a finding would provide novel evidence for an early influence of context on lexical processing in Chinese reading. Accordingly, we investigated this issue in an eye-movement experiment using the boundary paradigm and sentences containing two-character target words with high or low contextual predictability. Prior to the reader's gaze crossing an invisible boundary, each target word was shown normally (i.e. a valid preview) or with its two characters either transposed or replaced by unrelated characters to create invalid nonword previews. These invalid previews reverted to the target word once the reader's gaze crossed the invisible boundary. The results showed larger preview benefits (i.e. a decrease in fixation times) for target words following transposed-character than substituted-character previews, revealing a transposed-character effect similar to that in previous research. In addition, a word predictability effect (shorter fixation times for words with high than low predictability) was observed following both valid and transposed-character previews, but not substituted-character previews. The findings therefore reveal that context can influence an early stage of lexical processing in Chinese reading during which character order is processed flexibly.

Adequate access to healthcare and added life expectancy among older adults in China.

BACKGROUND: Adequate access to healthcare is associated with lower risks of mortality at older ages. However, it is largely unknown how many more years of life can be attributed to having adequate access to healthcare compared with having inadequate access to healthcare. METHOD: A nationwide longitudinal survey of 27,794 older adults aged 65+ in mainland China from 2002 to 2014 was used for analysis. Multivariate hazard models and life table techniques were used to estimate differences in life expectancy associated with self-reported access to healthcare (adequate vs. inadequate). The findings were assessed after adjusting for a wide range of demographic factors, socioeconomic status, family/social support, health practices, and health conditions. RESULTS: At age 65, adequate access to healthcare increased life expectancy by approximately 2.0-2.5 years in men and women and across urban-rural areas compared with those who reported inadequate access to healthcare. At age 85, the corresponding increase in life expectancy was 1.0-1.2 years. After adjustment for multiple confounding factors, the increase in life expectancy was reduced to approximately 1.1-1.5 years at age 65 and 0.6-0.8 years at age 85. In women, the net increase in life expectancy attributable to adequate access to healthcare was 6 and 8% at ages 65 and 85, respectively. In men, the net increases in life expectancy were generally greater (10 and 14%) and consistent after covariate adjustments. In contrast, the increase in life expectancy was slightly lower in rural areas (2.0 years at age 65 and 1.0 years at age 85) than in urban areas (2.1 years at age 65 and 1.1 years age 85) when no confounding factors were taken into account. However, the increase in life expectancy was greater in rural areas (1.0 years at age 65 and 0.6 years at age 85) than in urban areas (0.4 years at age 65 and 0.2 years at age 85) after accounting for socioeconomic and other factors. CONCLUSIONS: Adequate access to healthcare was associated with longer life expectancy among older adults in China. These findings have important implications for efforts to improve access to healthcare among older populations in China.

Transformable nanoparticles triggered by cancer-associated fibroblasts for improving drug permeability and efficacy in desmoplastic tumors.

Cancer-associated fibroblasts (CAFs) are important barriers for nanoparticles (NPs) to deeply penetrate into tumors and severely limit the antitumor efficacy of nanomedicines. Herein, we proposed a CAF-triggered transformable drug delivery system based on a cleavable peptide responsive to fibroblast activation protein-α (FAP-α) specifically overexpressed on the surface of CAFs. The NPs were composed of cationic poly(amidoamine) (PAMAM) dendrimers cross-linked by our designed peptide, a chemotherapeutical drug was incorporated onto PAMAM using disulfide bonds and finally, hyaluronic acid (HA) was conjugated to improve the tumor targetability as well as biocompatibility through electrostatic interactions. These NPs had an initial size of ∼200 nm and negative zeta potential favorable for stable blood circulation; however, after docking with CAFs, they dissociated into smaller NPs and exposed the relative positive surface charge to facilitate penetration and enter the tumor cells together with CAFs. An interesting finding was that this system intracellularly released different levels of drugs in these two kinds of cells, which was beneficial for the disruption of the stromal barrier and increasing the local drug accumulation. Our investigation confirmed that the constructed system could alleviate the biological barriers and hold promising therapeutic efficiency for desmoplastic solid tumors.

Objective and subjective financial status and mortality among older adults in China.

The association between financial status and mortality in older adults is well documented. However, it is unclear whether the association may vary by objective and subjective indicators of financial status. To examine this issue, we used the latest four waves (2005, 2008/2009, 2011/2012, and 2014) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) of community-residing adults aged 65 and older (n = 25,954). Financial status was assessed using eight objective, subjective, and culturally-oriented measures to capture various dimensions of financial resources at older ages. Multivariate hazard models were used to examine how different indicators of financial status were associated with subsequent mortality in all older adults and by age, gender, and urban-rural residence. Results showed that higher financial status-either objective or subjective-was associated with lower risks of mortality. Subjective assessments of financial status had stronger associations with mortality than objective assessments. The patterns were generally similar between young-old (aged 65-79) and the oldest-old (aged 80+), between women and men, and between rural and urban areas. Together, the findings offer new evidence to help improve the socioeconomic gradient in mortality among older adults in China.

Greater financial resources are associated with lower self-perceived uselessness among older adults in China: The urban and rural difference.

OBJECTIVES: This study aims to address whether associations between financial resources and self-perceived uselessness are different by urban-rural residence and whether the associations are stronger for subjectively-measured than for objectively-measured financial resources among older adults. DESIGN AND METHODS: We relied on the latest four waves of data of a China nationally representative survey with 25,954 community-residing respondents in 2005-2014. Self-perceived uselessness was classified into four categories: high, moderate, and low frequencies plus unable to answer the question. Financial resources included six objectively- or subjectively-measured variables and two culturally-measured variables. Multinomial logistic models were employed for the purposes, taking the low frequency as the reference category and adjusting for intrapersonal correlation. RESULTS: Better financial resources, either objectively- or subjectively-measured, are associated with lower risk of the high and moderate frequencies of self-perceived uselessness relative to the low frequency in both urban and rural older adults. Subjectively-measured financial resources have more pronounced associations with self-perceived uselessness than objectively-measured financial resources in both urban and rural areas. Upward wealth transfer, one culturally-measured financial factor, is associated with greater relative risk of the high vs. the low frequency in urban areas, but the association is not significant in rural areas. In both urban and rural areas, the downward transfer, another culturally-measured financial factor, is associated with lower relative risk of the high frequency vs. the low frequency. CONCLUSIONS: The associations between financial resources and self-perceived uselessness differ between urban and rural areas. Subjectively-measured financial resources tend to be more strongly associated with self-perceived uselessness.

Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform.

Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment. STATEMENT OF SIGNIFICANCE: In recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform.