Miracle-dz/UniFAR-FTUs huggingface dataset:
Editorial: Cellular Mechanisms of Aging and Longevity in Oral Health and Disease

The aging adult population will continue to grow well into the next two decades [1] with a rise expected in diseases of inflammaging, as reviewed by Clark et al. Particular emphasis in this review is placed on periodontitis (PD), one of the most common age-related inflammatory disease [2]. PD is comorbid with many inflammaging diseases such as type 2 diabetes, heart disease [3], cancer [4], and Alzheimer’s disease [5]. Collectively these comorbid diseases constitute a major cause of mortality and morbidity on the globe [3–6]. Intense efforts are needed to identify the pathogenic mechanisms involved, and to facilitate the development of novel therapeutic agents. COVID 19 deaths have also been linked to advanced age [7], with human [8] and murine studies [9] beginning to reveal the destructive inflammatory lung responses [10]. Similar studies are defining the destructive cellular immune responses in PD [11], with particular emphasis on in situ studies in humans [12] and in mice [13], documenting an important role for unregulated activation of gingival dendritic cells and T cells in situ in promotion of Th17 driven alveolar bone loss. Understanding how these immune cells interact with the oral microbiome in young and aged subjects and promote systemic dissemination of oral pathogens [3, 12, 14] is of particular significance. Ebersole et al. examined the age-related changes of innate antimicrobial factors at oral mucosa and secretions in non-human primates subjected to experimental PD. Antimicrobial factors in the oral environment must battle microbes such as the keystone periodontal pathogen Porphyromonas gingivalis [15]. This species has been discovered in the brains of Alzheimer’s disease patients [16], and invades dendritic cells, resulting in activation of the senescence associated secretory phenotype (SASP). The SASP releases a burst of exosomes into the milieu, promoting senescence in normal bystander immune cells [17]. Parkinson and Prime have provided a Minireview of classical cellular senescence and its implications for oral tumor surveillance and therapeutics, thus rounding out this topical section.
A Pituitary Carcinoma Patient With Cerebrospinal Fluid Dissemination Showing a Good Response to Temozolomide Combined With Whole-Brain and Spinal Cord Radiotherapy: A Case Report and Literature Review

Pituitary carcinoma (PC) is extremely rare, with its incidence only accounting for 0.1%-0.2% of pituitary tumor (PT). Existing histological features, including invasiveness, cellular pleomorphism, nuclear atypia, mitosis, necrosis, etc., can be observed in pituitary adenoma (PA), invasive PA (IPA) and PC. Invasion is not the basis for the diagnosis of PC. The diagnosis of PC is often determined after the metastases are found, hence early diagnosis is extraordinarily difficult. Owing to the conventional treatment for PC may not be effective, a large portion of patients survived less than one year after diagnosis. Therefore, it is of great significance to find an efficacious treatment for PC. We report a rare case of sparsely granulated somatotroph carcinoma with cerebrospinal fluid dissemination showing a favorable treatment response to temozolomide (TMZ) combined with whole-brain and spinal cord radiotherapy.
Exploring the Multidisciplinary Factors Affecting Sports Talent Identification

Talent is one of the most significant factors to promote the development of sports undertakings. The present study aimed to explore the factors affecting the identification of sports talents in China's physical education curriculum. Based on the literature review, this study puts forward a model to examine the influencing factors of sports talent identification in China's physical education curriculum using structural equation modeling and uses the structural equation modeling and factor analysis method to verify the hypothesis combined with the results of 310 effective questionnaires. The article summarizes influencing factors from four aspects, namely, physical, psychological, coach, and environmental factors. On the basis of relevant literature, the hypothesis model was established by structural equation modeling. The results show that the main factors affecting the identification of sports talents in the physical education curriculum are personal physical quality performance, psychological quality, coach's knowledge, and the identification policies of schools to sports talents. The conclusion of this study can provide guidance for the reform of the physical education curriculum, the growth of sports talents, and the development of sports talents in China.
The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression

Background β-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of β-elemene on CCA need to be further investigated. Methods A thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of β-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following β-elemene treatment. Immunohistochemical methods were applied to detect β-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. β-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells. Results In the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the β-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by β-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. β-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of β-elemene and displays an important role in predicting tumor recurrence in CCA patients. Conclusions These findings proved that long-term use of β-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, β-elemene exerted its anticancer potential partially by restoring the expression of PCDH9.
Bromopropylate Imidazoliumyl Substituted Silicon Phthalocyanine for Mitochondria-Targeting, Two-Photon Imaging Guided in Vitro Photodynamic Therapy

Maximization of phototoxic damage on tumor is essential for effective anticancer photodynamic therapy (PDT). Highly cancer-cell-organelle-specific delivery of efficient photosensitizers (PSs) in vitro and in vivo is in great demand. In this paper, a novel water-soluble mitochondria targeted cationic bromopropylate imidazoliumyl axially substituted silicon (IV) phthalocyanine (Br-ID-SiPc) is developed to improve PDT efficiency by enhancing the subcellular localization of photosensitizers. Benefiting from the targeting capability of bromopropylate imidazoliumyl, Br-ID-SiPc can selectively accumulate in mitochondria after cellular uptake, this process could be tracked by two-photon imaging. Br-ID-SiPc effectively damaged the circular plasmid DNA of mitochondria and induced HO-8910 cells apoptosis. Our results indicate that Br-ID-SiPc is a potential photosensitizer which can be used as a mitochondria-targeting and two-photon fluorescent imaging molecule for PDT of cancers.
The Association Between Different Types of Dietary Carbohydrates and Colorectal Cancer: A Case-Control Study

Background Several factors such as genetics and dietary intake are involved in the development of colorectal cancer (CRC). Higher intake of dietary carbohydrates may be associated with an increased risk of CRC. This study aimed to investigate the association between different types of dietary carbohydrates and CRC. Methods This hospital-based case–control study was carried out from June 2020 to May 2021 on 480 randomly selected participants including 160 CRC patients and 320 healthy controls aged 35–70 years in Firoozgar hospital, Tehran, Iran. Dietary intake was assessed using Food Frequency Questionnaire (FFQ). Nutritionist IV software was used to determine the intake of calorie and various forms of dietary carbohydrates including total carbohydrate, simple sugar, glucose, fructose, galactose, sucrose, lactose, and maltose. Results The average daily intake of calorie, carbohydrates, sugar, glucose, fructose, sucrose, and maltose were significantly higher among CRC cases compared to the controls (All P < 0.05). The logistic regression found significant associations between CRC with dietary intake of carbohydrates (OR = 1.009, CI 95%: 1.003–1.01, P = 0.002), sugar (OR = 1.02, CI 95%: 1.01–1.03, P < 0.001), glucose (OR = 1.06, CI 95%: 1.01–1.11, P = 0.009), fructose (OR = 1.31, CI 95%: 1.19–1.43, P < 0.001), sucrose (OR = 1.19, CI 95%: 1.12.−1.25, P < 0.001), maltose (OR = 9.03, CI 95%: 3.93–20.78, P < 0.001), galactose (OR = 1.31, CI 95%: 1.07–1.6, P = 0.008), and lactose (OR = 1.009, CI 95%: 1.01–1.18, P = 0.02). This association remained significant after adjustment for sex and age (except for galactose and lactose), and additional adjustment for sleep, tobacco, and alcohol level, and further adjustment for calorie intake and body mass index (BMI) (except for glucose). Conclusions A positive association was found between CRC and dietary intake of carbohydrates, sugar, fructose, sucrose, and maltose. Following a low-carbohydrate, low-sugar diet may help prevent CRC. Future longitudinal studies are warranted to confirm these findings.
Early Discovery of Children With Lysosomal Acid Lipase Deficiency With the Universal Familial Hypercholesterolemia Screening Program

Lysosomal acid lipase deficiency (LAL-D) is an autosomal recessive lysosomal storage disorder, caused by homozygous or compound heterozygous pathogenic variants in the LIPA gene. Clinically, LAL-D is under- and misdiagnosed, due to similar clinical and laboratory findings with other cholesterol or liver misfunctions. As a part of the Slovenian universal familial hypercholesterolemia (FH) screening, LAL-D is screened as a secondary condition among other rare dyslipidemias manifesting with hypercholesterolemia. Out of 669 children included, three were positive for a homozygous disease-causing splicing variant NM_000235. 4: c.894G > A (NP_000226.2:p. Gln298Gln) in the LIPA gene (NG_008194.1). The mean age by the diagnosis of LAL-D was 9.8 ± 0.9 years. Moreover, all three LAL-D-positive children had an important elevation of transaminases and decreased activity of the lysosomal acid lipase enzyme. Abdominal MRI in all children detected an enlarged liver but a normal-sized spleen. In conclusion, universal FH screening algorithms with the confirmatory genetic analysis in the pediatric population enable also rare dyslipidemia detection at an early age. An important clinical criterion for differentiation between FH and the LAL-D-positive children has elevated transaminase levels (AST and ALT). In all three LAL-D positive children, an improvement in cholesterol and transaminase levels and steatosis of the liver has been seen after early treatment initiation.
Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma

Background The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.
Increasing Readiness to Grow Traffic Safety Culture and Adopt the Safe System Approach: A Story of the Washington Traffic Safety Commission

Growing traffic safety culture and adopting the Safe System approach are strategies to support achieving a vision of zero traffic fatalities and serious injuries. However, adopting these strategies requires organizational change. Change is more likely to occur and be sustained by growing organizational readiness for change. Change readiness is driven by perceptions that 1) the change aligns with the organization’s culture 2) the organization (e.g., leadership, staff), is committed to the change, and 3) the organization has the resources necessary to make the change. The Washington Traffic Safety Commission has been engaged in a change process that focuses on growing traffic safety culture and adopting the Safe System approach for many years. This article shares insights from their journey that other organizations can use to bolster their own change efforts.
Genome Sequence Variations of Infectious Bronchitis Virus Serotypes From Commercial Chickens in Mexico

New variants of infectious bronchitis viruses (IBVs; Coronaviridae) continuously emerge despite routine vaccinations. Here, we report genome sequence variations of IBVs identified by random non-targeted next generation sequencing (NGS) of vaccine and field samples collected on FTA cards from commercial flocks in Mexico in 2019–2021. Paired-ended sequencing libraries prepared from rRNA-depleted RNAs were sequenced using Illumina MiSeq. IBV RNA was detected in 60.07% (n = 167) of the analyzed samples, from which 33 complete genome sequences were de novo assembled. The genomes are organized as 5'UTR-[Rep1a-Rep1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b]-3'UTR, except in eight sequences lacking non-structural protein genes (accessory genes) 4b, 4c, and 6b. Seventeen sequences have auxiliary S2' cleavage site located 153 residues downstream the canonically conserved primary furin-specific S1/S2 cleavage site. The sequences distinctly cluster into lineages GI-1 (Mass-type; n = 8), GI-3 (Holte/Iowa-97; n = 2), GI-9 (Arkansas-like; n = 8), GI-13 (793B; n = 14), and GI-17 (California variant; CAV; n = 1), with regional distribution in Mexico; this is the first report of the presence of 793B- and CAV-like strains in the country. Various point mutations, substitutions, insertions and deletions are present in the S1 hypervariable regions (HVRs I-III) across all 5 lineages, including in residues 38, 43, 56, 63, 66, and 69 that are critical in viral attachment to respiratory tract tissues. Nine intra-/inter-lineage recombination events are present in the S proteins of three Mass-type sequences, two each of Holte/Iowa-97 and Ark-like sequence, and one each of 793B-like and CAV-like sequences. This study demonstrates the feasibility of FTA cards as an attractive, adoptable low-cost sampling option for untargeted discovery of avian viral agents in field-collected clinical samples. Collectively, our data points to co-circulation of multiple distinct IBVs in Mexican commercial flocks, underscoring the need for active surveillance and a review of IBV vaccines currently used in Mexico and the larger Latin America region.
The Value of Laparoscopic Simultaneous Colorectal and Hepatic Resection for Synchronous Colorectal Cancer Liver Metastasis: A Propensity Score Matching Study

Purpose The aim of this study is to investigate the value of total laparoscopic simultaneous colorectal and hepatic resection in patients with synchronous colorectal cancer liver metastases (sCRLMs). Methods sCRLM patients who underwent simultaneous resection from December 2014 to December 2018 in Shanghai Cancer Center, Fudan University were recruited and analyzed retrospectively. The patients were divided into laparoscopic, open, and hybrid surgery groups. The intraoperative information, postoperative short-term outcome, and long-term survival were compared among the three groups. Propensity score matching (PSM) was performed to balance baselines. Results A total of 281 patients were recruited. After PSM, 34 patients were selected from both the laparoscopic and the open surgery group. Forty-seven patients were also selected from both the laparoscopic and the hybrid surgery group. The clinicopathologic baselines between the laparoscopic surgery group and the other two groups were well matched. All the operation-related indicators between laparoscopic surgery and hybrid surgery were similar. However, compared with open surgery, laparoscopic surgery showed significantly longer operation time (229.09 ± 10.94 min vs. 192.24 ± 9.49 min, p = 0.013) and less intraoperative blood loss [100.00 (50.00–300.00) ml vs. 200.00 (150.00–400.00) ml, p = 0.021]. For postoperative morbidity, there was no significant difference between the laparoscopic surgery group and the hybrid or the open surgery group (23.40% vs. 31.91% and 17.65% vs. 26.47%, p = 0.356 and p = 0.380). Long-term survival analysis showed that there were no significant differences in all 1-, 3-, and 5-year overall survival, liver recurrence-free survival (RFS), and whole RFS between laparoscopic surgery and hybrid surgery (p = 0.334, p = 0.286, and p = 0.558) or open surgery (p = 0.230, p = 0.348, and p = 0.450). Conclusions Laparoscopic simultaneous resection for sCRLM shows slight advantages in surgical safety and short-term outcome, and does not compromise long-term survival.
Does Orexin B-Binding Receptor 2 for Orexins Regulate Testicular and Epididymal Functions in Normal and Cryptorchid Dogs?

Orexins A (OXA) and B (OXB) and the receptors 1 (OX1R) and 2 (OX2R) for orexins are hypothalamic peptides found in several mammalian organs and participated to the control of a wide assortment of physiological and pathological functions. The distribution of OXA and OX1R has been extensively studied in the male gonad of mammals. Here, we examined the expression and localization of OXB and OX2R as well as their possible involvement in the regulation of testicular and epididymal functions, in healthy and cryptorchid dogs, employing some techniques such as immunohistochemistry, Western blotting, and real-time RT-PCR. In vitro tests were also carried out for evaluating the steroidogenic effect of OXB. OXB and OX2R were expressed in spermatocytes, spermatids, and Leydig cells in normal testis. Their localization was restricted to Sertoli and Leydig cells in cryptorchid conditions. OXB was found to be localized in all tracts of both normal and cryptorchid epididymis, whereas OX2R was found only in the caput. Because the small molecular weight of the peptides OXA and OXB, the expression of their precursor prepro-orexin (PPO), OX1R, and OX2R proteins and mRNAs were investigated by means of Western blot and real-time RT-PCR analyses, respectively, in all tested groups of. In particular, the mRNA level expression of all three genes was higher in cryptorchid dogs than in normal ones. In vitro tests demonstrated that OXB—by binding OX2R—is not involved in testicular steroidogenic processes. Therefore, the findings of this study might be the basis for further functional and molecular studies addressing the possible biochemical effects of OXB and OX2R in normal and pathological conditions of the male reproductive system.
Lytic Bacteriophage PZL-Ah152 as Biocontrol Measures Against Lethal Aeromonas hydrophila Without Distorting Gut Microbiota

Phage therapy is an alternative approach to overcome the problem of multidrug resistance in bacteria. In this study, a bacteriophage named PZL-Ah152, which infects Aeromonas hydrophila, was isolated from sewage, and its biological characteristics and genome were studied. The genome contained 54 putative coding sequences and lacked known putative virulence factors, so it could be applied to phage therapy. Therefore, we performed a study to (i) investigate the efficacy of PZL-Ah152 in reducing the abundance of pathogenic A. hydrophila strain 152 in experimentally infected crucian carps, (ii) evaluate the safety of 12 consecutive days of intraperitoneal phage injection in crucian carps, and (iii) determine how bacteriophages impact the normal gut microbiota. The in vivo and in vitro results indicated that the phage could effectively eliminate A. hydrophila. Administering PZL-Ah152 (2 × 109 PFU) could effectively protect the fish (2 × 108 CFU/carp). Furthermore, a 12-day consecutive injection of PZL-Ah152 did not cause significant adverse effects in the main organs of the treated animals. We also found that members of the genus Aeromonas could enter and colonize the gut. The phage PZL-Ah152 reduced the number of colonies of the genus Aeromonas. However, no significant changes were observed in α-diversity and β-diversity parameters, which suggested that the consumed phage had little effect on the gut microbiota. All the results illustrated that PZL-Ah152 could be a new therapeutic method for infections caused by A. hydrophila.
Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive “cytokines storm”, main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.