Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii.

Iron is an indispensable nutrient for the survival of Toxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host's "nutritional immunity" barrier and compete with the host for iron. Since T. gondii can infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth of T. gondii. Iron accumulation disrupted the redox balance of T. gondii while enhancing the parasite's ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.

Two Molecular Plasma-Based Diagnostic Methods to Evaluate Early Infection of Schistosoma japonicum and Schistosomiasis Japonica.

The prevalence and infectious intensity of schistosomiasis japonica has decreased significantly in China in the past few decades. However, more accurate and sensitive diagnostic methods are urgently required for the further control, surveillance, and final elimination of the disease. In this study, we assessed the diagnostic efficacy of a real-time fluorescence quantitative PCR (qPCR) method and recombinase polymerase amplification (RPA) combined with a lateral-flow dipstick (LFD) assay for detecting early infections of Schistosoma japonicum and different infection intensities. The sensitivity of the qPCR at 40 days post-infection (dpi) was 100% (8/8) in mice infected with 40 cercariae, which was higher than in mice infected with 10 cercariae (90%, 9/10) or five cercariae (77.8%, 7/9). The results of the RPA-LFD assays were similar, with sensitivities of 55.6% (5/9), 80% (8/10), and 100% (8/8) in mice infected with 5, 10, and 40 cercariae, respectively. In goats, both the qPCR and RPA-LFD assays showed 100% (8/8) sensitivity at 56 dpi. In the early detection of S. japonicum infection in mice and goats with qPCR, the first peak in positivity appeared at 3-4 dpi, when the positivity rate exceeded 40%, even in the low infection, intensity mice. In the RPA-LFD assays, positive results first peaked at 4-5 dpi in the mice, and the positivity rate was 37.5% in the goats at 1 dpi. In conclusion, neither of the molecular methods produced exceptional results for the early diagnosis of S. japonicum infection. However, they were useful methods for the regular diagnosis of schistosomiasis in mice and goats.

Photobiocatalytic Strategies for Organic Synthesis.

Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated organic synthesis, most reactions involve molecules operating from their ground states. Over the past 25 years, there has been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic processes involve a diverse array of reaction mechanisms that are complementary to one another. This comprehensive review will describe the state-of-the-art strategies in photobiocatalysis for organic synthesis until December 2022. Apart from reviewing the relevant literature, a central goal of this review is to delineate the mechanistic differences between the general strategies employed in the field. We will organize this review based on the relationship between the photochemical step and the enzymatic transformations. The review will include mechanistic studies, substrate scopes, and protein optimization strategies. By clearly defining mechanistically-distinct strategies in photobiocatalytic chemistry, we hope to illuminate future synthetic opportunities in the area.

[Oral health and hygiene behavior in chronic renal failure patients].

PURPOSE: To investigate the oral health and hygiene behavior of chronic renal failure(CRF) patients in Shenzhen, so as to provide basis for formulating education for them. METHODS: The history of renal failure, oral health status and oral health care behavior of 336 patients with chronic renal failure(CRF) in the hemodialysis center of Shenzhen Second People's Hospital were investigated by questionnaire and oral examinations. RESULTS: At an average, dialysis was required for 3.2 years. The main cause of renal failure was glomerulonephritis in 49.11% of patients, hypertensive kidney lesion in 19.35% and diabetic nephropathy in 15.77% of patients; 77.8% of them kept brushing teeth two or more than two times every day; 72.9% patients suffered from oral problems such as toothache in recent 12 months. The rate of visiting a dentist when having complaints was 21.7%. CONCLUSIONS: The state of oral health of CRF is worse than the general population of comparable age in China, while their hygiene behavior is better than the corresponding reference general population. However, their consciousness of dental treatment is poor. Therefore, health education for CRF patients should include knowledge about oral diseases complicated with CRF and correct medical philosophy.

Oral Cancer Incidence, Mortality, and Mortality-to-Incidence Ratio Are Associated with Human Development Index in China, 1990-2019.

The burden of oral cancer (OC) is closely related to economic development. We aimed to evaluate the burden of OC at different stages of economic development in China in terms of incidence, mortality, and mortality-to-incidence ratio (MIR) from 1990 to 2019. Data on cancer in China from 1990 to 2019 were obtained from the Global Burden of Disease 2019. Based on human development index (HDI), Chinese economic development was divided into three stages: low, medium, and high HDI stages. Mann-Whitney U-test was used to evaluate the differences in age-standardised incidence rates (ASIR), age-standardised mortality rates (ASMR), and MIR at various stages of HDI. Correlation and regression tests were conducted to examine the association amongst ASIR, ASMR, MIR, and HDI in OC. The estimated annual percentage changes (EAPCs) were calculated to assess the trend of ASIR, ASMR, and MIR. Significant differences were observed in terms of ASIR, ASMR, and MIR between groups (P < 0.001). The values of both sexes in the low HDI stage were lower than those of the medium and high HDI stages, except for MIR, in which the low HDI stage was the highest (P < 0.05). ASIR and ASMR of OC in males at the medium HDI stage showed the fastest growth rate with EAPC values of 5.64 (95% confidence interval, 95% CI, 5.20 to 6.08) and 4.42 (95% CI, 4.01 to 4.82), respectively. A strong positive correlation exists between HDI and ASIR (r = 0.96) and ASMR (r = 0.91) in both sexes from 1990 to 2019. During the high HDI stage, the ASIR and ASMR of OC were at a high level, but the ASIR halted the uptrend trend and ASMR showed a decreasing trend. Therefore, the HDI index has been positively correlated with the ASIR and ASMR of OC in China in the past 30 years, but this relationship may not be sustained as the economy develops. The health department should continue to allocate additional resources for the prevention and treatment of OC.

Characterization of aspartyl aminopeptidase from Schistosoma japonicum.

The tegument of schistosomes is the interface between the worm and the host environment. Some molecules distributed on the tegument participate in host-parasite interactions. Aspartyl aminopeptidase (AAP), identified on the tegument of Schistosoma japonicum (S. japonicum), facilitate protein turnover by acting in concert with other aminopeptidases. In this study, the gene encoding S. japonicum aspartyl aminopeptidase (SjAAP) was cloned, expressed and characterized. Quantitative real-time PCR analysis showed that SjAAP was expressed in all studied developmental stages. The transcript level was higher in 8, 14, 21, and 28 days old worms than the other detected stages. Moreover, the level of expression in 42-day-old male worms was significantly higher than that in females. The recombinant SjAAP (rSjAAP) was expressed as both supernatant and inclusion bodies in Escherichia coli BL21 cells. The enzymatic activity of rSjAAP was 4.45 U/mg. The Km and Vmax values for H-Asp-pNA hydrolysis were discovered to be 5.93 mM and 0.018 mM·min-1. Immunofluorescence analysis revealed that SjAAP is primarily distributed on the tegument and parenchyma of schistosomes. Western blot showed that rSjAAP possessed good immunogenicity. Although specific antibodies were produced in BALB/c mice vaccinated with rSjAAP emulsified with ISA 206 adjuvant, no significant reduction of worm burden and number of eggs in the liver was observed. Therefore, rSjAAP may not be suitable to act as a potential vaccine candidate against schistosomiasis japonica in mice. However, this study provides some foundation for further exploration of the biological function of this molecule.

The Potential Role of MicroRNA-124-3p in Growth, Development, and Reproduction of Schistosoma japonicum.

The microRNA-124-3p plays an important role in regulating development and neurogenesis. Previous microRNA sequencing analyses of Schistosoma japonicum revealed sja-miR-124-3p differential expression patterns in schistosomes from different hosts and at different developmental stages. This study explores the regulatory role of sja-miR-124-3p in S. japonicum development and reproduction. Quantitative reverse-transcription PCR (qRT-PCR) showed that the expression level of sja-miR-124-3p in S. japonicum from resistant hosts, such as Microtus fortis, and unsuitable hosts, such as rats and water buffalo, was significantly higher than that in mice and yellow cattle at the same developmental stage. Overexpressing sja-miR-124-3p in infected mice led to a hepatic egg reduction rate of 36.97%, smaller egg granulomas in the livers, increased liver weight, subsided hepatocyte necrosis, and diminished inflammatory cell infiltration. The width of female worms increased but decreased in males. The vitelline cells were irregular, swollen, or fused. The teguments and ventral sucker of males and females were swollen and broken, but the morphological changes were particularly notable in males. qRT-PCR and dual-luciferase reporter assay system were used to confirm the in-silico-predicted target genes, S. japonicum DEAD-box ATP-dependent RNA helicase 1 (sjDDX1) and DNA polymerase II subunit 2 (sjPOLE2). Our results showed that RNA interference (RNAi)-mediated sjDDX1 silencing in mice provided a 24.55% worm reduction rate and an 18.36% egg reduction rate, but the difference was not significant (p > 0.05). Thus, our findings suggest that sja-miR-124-3p has an important role in growth, development, and reproduction in S. japonicum. All these results will greatly contribute toward providing important clues for searching vaccine candidates and new drug targets against schistosomiasis.

Burden of Oral Cancer on the 10 Most Populous Countries from 1990 to 2019: Estimates from the Global Burden of Disease Study 2019.

BACKGROUND: Oral cancer (OC) is a common tumour that poses a threat to human health and imposes a heavy burden on countries. This study assessed the burden imposed by OC on the 10 most populous countries from 1990 to 2019 on the basis of gender, age and socio-demographic index. METHODS: Data on incidence, mortality, disability-adjusted life years (DALY) and corresponding age-standardised rates (ASR) for OC in the 10 most populous countries from 1990 to 2019 were derived from the Global Burden of Disease Study 2019. Estimated annual percentage changes were calculated to assess the trends of morbidity, mortality and DALY. The indicator that served as a proxy for survival rate was the supplement of mortality-to-incidence ratio (SMIR) (1 - (M/I)). RESULTS: The number of new cases, deaths and DALY have increased in all 10 countries in the past 30 years. Trends in age-standardised incidence rates (ASIR), age-standardised mortality rate (ASMR) and age-standardised DALY for OC in the 10 most populous countries varied. The SMIR increased in all countries, with most countries having an SMIR between 30% and 50%. In 2019, the United States had the highest SMIR at 76%, whereas Russia had the lowest at 21.7%. Incidence and mortality were close between male and female subjects in Japan, Indonesia, Mexico, India, Bangladesh and Pakistan. The incidence and mortality in male subjects in the United States, Russia, China and Brazil were two or more times those of female subjects. Gender difference was highest among patients aged 40-69 years. CONCLUSION: Trends and gender differences in ASIR, ASMR and age-standardised DALY for OC vary in the 10 most populous countries. Government cancer programs are often expensive to run, especially in countries with large populations. Policy makers need to take these differences into account when formulating policies.

Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins.

Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched sp3-sp3 linkages via sp3 C-N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization. In addition, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is within reach, thus providing a useful entry point for forging enantioenriched sp3-sp3 centers at remote sp3 C-H sites.

Development of a Recombinase Polymerase Amplification Assay for Schistosomiasis Japonica Diagnosis in the Experimental Mice and Domestic Goats.

Although the prevalence of schistosomiasis japonica has declined gradually in China, more accurate and sensitive diagnostic methods are urgently needed for the prevention and control of this disease. Molecular diagnostic methods are advantageous in terms of sensitivity and specificity, but they are time-consuming and require expensive instruments and skilled personnel, which limits their application in low-resource settings. In this study, an isothermal DNA amplification assay and recombinase polymerase amplification (RPA) combined with lateral flow dipstick (LFD) were set up. It was used to detect S. japonicum infections in experimental mice and domestic goats by amplifying a specific DNA fragment of S. japonicum. The lower limit of detection for the LFD-RPA assay was evaluated using dilutions of plasmid containing the target sequence. Cross-reactivity was evaluated using genomic DNA from eight other parasites. The effectiveness of the LFD-RPA assay was verified by assessing 36 positive plasma samples and 36 negative plasma samples from mice. The LFD-RPA assay and real-time PCR were also used to assess 48 schistosomiasis japonica-positive plasma samples and 53 negative plasma samples from goats. The LFD-RPA assay could detect 2.6 femtogram (fg) of S. japonicum target DNA (~39 fg genomic DNA of S. japonicum), only 10-fold less sensitive than real-time PCR assay. There was no cross-reactivity with DNA from the other eight parasites, such as Haemonchus contortus and Spirometra. The whole amplification process could be completed within 15 min at 39°C, and the results can be observed easily using the LFD. The sensitivity and specificity of the LFD-RPA assay were 97.22% (35/36, 95% CI, 85.47%-99.93%) and 100% (36/36, 95% CI, 90.26%-100%) in mice, and 93.75% (45/48, 95% CI, 82.80%-98.69%) and 100% (53/53, 95% CI, 93.28%-100%) in goats. By comparison, the sensitivity and specificity of real-time PCR were 100% (36/36, 95% CI, 90.26%-100%) and 100% (36/36, 95% CI, 90.26%-100%) for mice, and 97.92% (47/48, 95% CI, 88.93%-99.95%) and 100% (53/53, 95% CI, 93.28%-100%) for goats. The LFD-RPA assay exhibits high sensitivity and specificity for the diagnosis of schistosomiasis japonica, and it is an alternative method for diagnosis schistosomiasis japonica in low resource setting.

Research Achievements of Oral Submucous Fibrosis: Progress and Prospect.

Oral submucous fibrosis (OSMF) is a kind of chronic, insidious disease, and it is categorized into potentially malignant disorders (PMD), which poses a global and regional problem to public health. It is considered to be a multifactorial disease, such as due to areca nut chewing, trace element disorders, and genetic susceptibility. However, there is still no unanimous conclusion on its pathogenesis, diagnosis, and treatment strategies. Hence, this article provides a comprehensive review and prospect of OSMF research, providing scholars and clinicians with a better perspective and new ideas for the research and treatment of OSMF.

Preemptive Oral Etoricoxib on Health-Related Quality of Life after Mandibular Third Molar Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

This study was aimed at evaluating the use of oral etoricoxib for preemptive analgesia on the health-related quality of life (QoL) outcome after the extraction of mandibular third molar. The study population consisted of 60 participants that required extraction of a single partial bony impacted mandibular third molar under local anesthesia and met the inclusion criteria. The participants were randomized into two groups. The etoricoxib group orally received 60 mg etoricoxib 30 min before surgery, whereas the control group was given a placebo. The patients were assessed postoperatively after 1, 2, 3, 4, 5, 6, and 7 days using the United Kingdom oral health-related QoL questionnaire and visual analog scale for maximum postoperative pain. The total dose of ibuprofen rescue intake and total number of days the drug was taken were recorded. Surgical removal of impacted teeth had a negative influence on the patient's QoL across various physical, social, and psychological aspects. The scores for postoperative pain in the etoricoxib group were significantly lower than those in the control group on each postoperative observation day. The number of patients without analgesic rescue medication, the average amount, and total number of days emergency analgesics were taken were significantly lower in the etoricoxib group than in the control group. The etoricoxib group showed better QoL score than the control group. Preemptive oral etoricoxib is an effective therapeutic strategy for improving the QoL after surgical removal of the impacted lower third molar.

sp3 Bis-Organometallic Reagents via Catalytic 1,1-Difunctionalization of Unactivated Olefins.

A catalytic 1,1-difunctionalization of unactivated olefins en route to sp3 bis-organometallic B,B(Si)-reagents is described. The protocol is characterized by exceptional reaction rates, mild conditions, wide scope, and exquisite selectivity pattern, constituting a new platform to access sp3 bis-organometallics.

[Multidisciplinary team model for patients with oral cancer and systemic diseases: an expert consensus].

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.

[Relationship among areca nut, intracellular reactive oxygen species, and autophagy].

The relationship between areca nut as a primary carcinogen and oral cancer has been widely concerned. Areca can change the levels of reactive oxygen species (ROS) and autophagy in cells, and the levels of ROS and autophagy are closely related to the occurrence and development of tumors. This paper reviewed the relationships among areca nut, intracellular ROS, and autophagy.

Copper mediated C(sp2)-H amination and hydroxylation of phosphinamides.

Copper mediated C(sp2)-H amination and hydroxylation of arylphosphinic acid are accomplished by adopting phosphinamide as the directing group. This method is distinguished by its wide substrate scope and excellent functional group tolerance, thus allowing for the rapid preparation of organophosphorus compounds in organic synthesis.

Site-Selective 1,2-Dicarbofunctionalization of Vinyl Boronates through Dual Catalysis.

A modular, site-selective 1,2-dicarbofunctionalization of vinyl boronates with organic halides through dual catalysis is described. This reaction proceeds under mild conditions and is characterized by excellent chemo- and regioselectivity. It thus represents a complementary new technique for preparing densely functionalized alkyl boron architectures from simple and accessible precursors.

Site-Selective Catalytic Deaminative Alkylation of Unactivated Olefins.

A catalytic deaminative alkylation of unactivated olefins is described. The protocol is characterized by its mild conditions, wide scope, including the use of ethylene as substrate, and exquisite site-selectivity pattern for both α-olefins and internal olefins, thus unlocking a new catalytic platform to forge sp3-sp3 linkages, even in the context of late-stage functionalization.

Site-Selective Ni-Catalyzed Reductive Coupling of α-Haloboranes with Unactivated Olefins.

A mild, chemo- and site-selective catalytic protocol that allows for incorporating an alkylboron fragment into unactivated olefins is described. The use of internal olefins enables C-C bond-formation at remote sp3 C-H sites, constituting a complementary and conceptually different approach to existing borylation techniques that are currently available at sp3 centers.

Application of Delayed Surgical Managements in Patients with Stensen's Duct Injury.

The study aimed to retrospectively evaluate surgical treatment outcomes after delayed parotid gland and duct injuries. Nine patients subjected to parotid gland and duct injuries with 1- to 3-month treatment delay were retrospectively evaluated with special reference of etiology, past medical history, and injury location. Conservative treatment, microsurgical anastomosis, and diversion of salivary flow or ligation were chosen for delayed parotid gland and duct injuries concerning to their site of injury, time of repair and procedures. Assistant treatment as pressure dressing was adopted thereafter. All patients experienced an uneventful recovery at the time of finalizing the study. Two patients received Stensen's duct ligation, 5 received microsurgical anastomosis and 2 accepted salivary flow diversion for 5 patients with sialoceles and 4 patients with fistulas, and no re-occurrence was found. Facial paralysis occurred after surgery in 4 patients, and 3 of them recovered after the nerve nutrition treatment. Our study suggested that appropriate surgical treatment is efficient for the re-establishment of the tissue function and facial aesthetic for delayed injury of the parotid and its duct.