Clinical features and genetic spectrum of a multicenter Chinese cohort with myotonic dystrophy type 1.

BACKGROUND: As the most common subtype of adult muscular dystrophy worldwide, large cohort reports on myotonic dystrophy type I (DM1) in China are still lacking. This study aims to analyze the genetic and clinical characteristics of Chinese Han DM1 patients. METHODS: Based on the multicenter collaborating effort of the Pan-Yangtze River Delta Alliance for Neuromuscular Disorders, patients with suspected clinical diagnoses of DM1 were genetically confirmed from January 2020 to April 2023. Peak CTG repeats in the DMPK gene were analyzed using triplet repeat-primed PCR (TP-PCR) and flanking PCR. Time-to-event analysis of onset age in females and males was performed. Additionally, detailed clinical features and longitudinal changes from the disease onset in 64 DM1 patients were retrospectively collected and analyzed. The Epworth Sleepiness Scale and Fatigue Severity Scale were used to quantify the severity of daytime sleepiness and fatigue. RESULTS: Among the 211 genetically confirmed DM1 patients, the mean age at diagnosis was 40.9 ± 12.2 (range: 12-74) with a male-to-female ratio of 124:87. The average size of CTG repeats was 511.3 (range: 92-1945). Among the DM1 patients with comprehensive clinical data (n = 64, mean age 41.0 ± 12.0), the age at onset was significantly earlier in males than in females (4.8 years earlier, p = 0.026). Muscle weakness (92.2%), myotonia (85.9%), and fatigue (73.4%) were the most prevalent clinical features. The predominant involved muscles at onset are hands (weakness or myotonia) (52.6%) and legs (walking disability) (42.1%). Of them, 70.3% of patients had daytime sleepiness, 14.1% had cataract surgery, 7.8% used wheelchairs, 4.7% required ventilatory support, and 1.6% required gastric tubes. Regarding the comorbidities, 4.7% of patients had tumors, 17.2% had diabetes, 23.4% had dyspnea, 28.1% had intermittent insomnia, 43.8% experienced dysphagia, and 25% exhibited cognitive impairment. Chinese patients exhibited smaller size of CTG repeats (468 ± 139) than those reported in Italy (613 ± 623), the US (629 ± 386), and Japan (625 [302, 1047]), and milder phenotypes with less multisystem involvement. CONCLUSION: The Chinese Han DM1 patients presented milder phenotypes compared to their Caucasian and Japanese counterparts. A male predominance and an early age of onset were identified in male Chinese Han DM1 patients.

Proline-derived quinoline formamide compounds as human urate transporter 1 inhibitors with potent uric acid-lowering activities.

We report the design and synthesis of a series of proline-derived quinoline formamide compounds as human urate transporter 1 (URAT1) inhibitors via a ligand-based pharmacophore approach. Structure-activity relationship studies reveal that the replacement of the carboxyl group on the polar fragment with trifluoromethanesulfonamide and substituent modification at the 6-position of the quinoline ring greatly improve URAT1 inhibitory activity compared with lesinurad. Compounds 21c, 21e, 24b, 24c, and 23a exhibit potent activities against URAT1 with IC50 values ranging from 0.052 to 0.56 µM. Furthermore, compound 23a displays improved selectivity towards organic anion transporter 1 (OAT1), good microsomal stability, low potential for genotoxicity and no inhibition of the hERG K+ channel. Compounds 21c and 23a, which have superior pharmacokinetic properties, also demonstrate significant uric acid-lowering activities in a mouse model of hyperuricemia. Notably, 21c also exhibits moderate anti-inflammatory activity related to the gout inflammatory pathway. Compounds 21c and 23a with superior druggability are potential candidates for the treatment of hyperuricemia and gout.

The Active Glucuronide Metabolite of the Brain Protectant IMM-H004 with Poor Blood-Brain Barrier Permeability Demonstrates a High Partition in the Rat Brain via Multiple Mechanisms.

BACKGROUND: Glucuronidation is an essential metabolic pathway for a variety of drugs. IMM-H004 is a novel neuroprotective agent against ischemic stroke, and its glucuronide metabolite IMM-H004G exhibits similar pharmacological activity. Despite possessing a higher molecular weight and polarity, brain exposure of IMM-H004G is much higher than that of IMM-H004. This study aimed to investigate the brain metabolism and transport mechanisms of IMM-H004 and IMM-H004G. METHODS: First, the possibility of IMM-H004 glucuronidation in the brain was evaluated in several human brain cell lines and rat homogenate. Subsequently, the blood-brain barrier carrier-mediated transport mechanism of IMM-H004 and IMM-H004G was studied using overexpression cell models. In addition, intracerebroventricular injection, in situ brain perfusion model, and microdialysis/microinjection techniques were performed to study the distribution profiles of IMM-H004 and IMM-H004G. RESULTS: IMM-H004 could be metabolized to IMM-H004G in both rat brain and HEB cells mediated by UGT1A7. However, IMM-H004G could not be hydrolyzed back into IMM-H004. Furthermore, the entry and efflux of IMM-H004 in the brain were mediated by the pyrilamine-sensitive H+/OC antiporter and P-gp, respectively, while the transport of IMM-H004G from the blood to the brain was facilitated by OATP1A2 and OATP2B1. Ultimately, stronger concentration gradients and OATP-mediated uptake played a critical role in promoting greater brain exposure of IMM-H004G. CONCLUSIONS: The active glucuronide metabolite of the brain protectant IMM-H004 with poor blood-brain barrier permeability demonstrates a high partition in the rat brain via multiple mechanisms, and our findings deepen the understanding of the mechanisms underlying the blood-brain barrier metabolism and transport of active glucuronide conjugates.

Design, Synthesis, and Bioevaluation of Novel Reversibly Photoswitchable PI3K Inhibitors Based on Phenylazopyridine Derivatives toward Light-Controlled Cancer Treatment.

Photopharmacology is an emerging approach for achieving light-controlled drug activity. Herein, we design and synthesize a novel series of photoswitchable PI3K inhibitors by replacing a sulfonamide moiety with an azo group in a 4-methylquinazoline-based scaffold. Through structure-activity relationship studies, compound 6g is identified to be effectively switched between its trans- and cis-configuration under irradiation with proper wavelengths. Molecular docking studies show the cis-isomer of 6g is favorable to bind to the PI3K target, supporting compound 6g in the PSS365 (cis-isomer enriched) was more potent than that in the PSSdark (trans-isomer dominated) in PI3K enzymatic assay, cell antiproliferative assay, Western blotting analysis on PI3K downstream effectors, cell cycle analysis, colony formation assay, and wound-healing assay. Relative to the cis-isomer, the trans-isomer is more metabolically stable and shows good pharmacokinetic properties in mice. Moreover, compound 6g inhibits tumor growth in nude mice and a zebrafish HGC-27 xenograft model.

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation.

The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI50 in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Myasthenic crisis in thymoma-associated myasthenia gravis: a multicenter retrospective cohort study.

Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P<0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6-111] vs. 33.2 ± 23.42 days [7-120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6-111] vs. 34.21±18.87 days [12-82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis.

Persulfate enhanced removal of bisphenol A by copper oxide/reduced graphene oxide foam: Influencing factors, mechanism and degradation pathway.

The CuO/reduced graphene oxide foam (CuO/RGF) with excellent recyclability was prepared via hydrothermal method followed by freeze drying treatment for bisphenol A (BPA) removal via activating peroxydisulfate (PDS). SEM, XRD, XPS, FT-IR, BET, and TG techniques were used to investigate the structure and property of CuO/RGF. The effect of degradation conditions (pH, PDS amount, Cl-, HCO3-, HA and FA) on BPA removal by CuO/RGF were investigated. The result presented that CuO nanosheet was inserted into the RGF carrier with three-dimensional structure. The degradation rate constant of BPA over CuO/RGF (0.00917 min-1) was 1.24 and 6.46 times higher than those of BPA over CuO (0.00714 min-1) and RGF (0.00142 min-1). More importantly, the pore structure of RGF can successfully limit the release of Cu (II) compared to pure CuO. According to quenching test as well as electron spin resonance (EPR) spectra, BPA degradation was triggered by 1O2, •OH and SO4•-, which was the combination of nonradical (1O2) and radical activation of PDS (•OH and SO4•-). The possible degradation route of BPA was proposed based on intermediates obtained by combining solid phase extraction pretreatment technique with high performance liquid-mass spectrometry. After assessing the viability of MCF-7 cells, we can see that the estrogenic activities of treated solution reduced without producing stronger endocrine disruptors.

Effect of zero-valent iron nanoparticles on taxonomic composition and hydrogen production from kitchen waste.

This study investigated the effects of varying zero-valent iron (ZVI) (0 to 5,000 mg/L) on fermentative hydrogen (H2) production, metabolic pattern, and taxonomic profile by using kitchen waste as substrate. The study demonstrated that the supplementation of 500 mg ZVI/L resulted in the highest H2 yield (219.68 ± 11.19 mL H2/g-volatile solids (VS)added), which was 19% higher than the control. The metabolic pattern analysis showed that acetic and butyric acid production primarily drove the H2 production. The taxonomic analysis further revealed that Firmicutes (relative abundance (RA): 80-96%) and Clostridium sensu stricto 1 (RA: 68-88%) were the dominant phyla and genera, respectively, during the exponential gas production phase, supporting the observation of accumulation of acetic and butyric acids. These findings suggest that supplementation of ZVI can enhance H2 production from organic waste and significantly influence the metabolic pattern and taxonomic profile, including the metalloenzymes.

Myasthenia-like paraneoplastic syndrome with multiple cranial nerve tumor infiltration: A case report and literature review.

RATIONALE: Approximately 0.001% of patients with cancer have paraneoplastic nerve system syndrome, which can affect the central nervous system, neuromuscular junction, or peripheral nervous system. Although myasthenia gravis (MG) may exist as a thymic paraneoplastic syndrome (PNPS), its association with primary lung cancer remains unknown. PATIENT CONCERNS: A 55-year-old female presented with slurred speech, weakness in chewing, sporadic difficulty in swallowing, and weakness in both lower limbs for half a year. DIAGNOSES: Based on cerebrospinal fluid and electromyography findings, we present the case of a female patient diagnosed with overlapping multicranial nerve tumor infiltration and MG-like neurological PNPS secondary to lung adenocarcinoma. INTERVENTIONS: The patient received intrathecal injections of pemetrexed and neurotrophic (vitamin B) therapy before ceasing chemoradiotherapy and chose cabozantinib on her own. OUTCOMES: Weakness of the proximal limbs, choking cough, and chewing problems did not improve significantly. LESSONS: Although it is unclear why MG coexists with lung cancer, it is probable that MG is a paraneoplastic condition. Cerebrospinal fluid testing should be carried out along with electrophysiological, serological, and pharmacological procedures pertinent to the diagnosis of MG to thoroughly examine if people simultaneously experience MG-like PNPS and tumor growth. Starting immunotherapy and anticancer medication at the same time that tumor development and MG-like syndrome are discovered is crucial.

Clinical outcomes of diode laser as an adjunct to nonsurgical periodontal therapy for residual periodontal pockets in mandibular second molars-a randomized controlled clinical trial.

OBJECTIVES: The aim of this study was to evaluate the clinical outcomes of diode laser as an adjunct to nonsurgical periodontal therapy (NSPT) for residual periodontal pockets in mandibular second molars. MATERIALS AND METHODS: Sixty-seven mandibular second molars (154 residual periodontal pockets) were recruited into the study and randomly assigned to the Laser + NSPT group and the NSPT group. The Laser + NSPT group underwent NSPT adjunct with diode laser radiation (wavelength: 810 nm, power: 1.5 W, 40 s maximum), while the NSPT group underwent nonsurgical periodontal therapy alone. Clinical parameters were measured at baseline (T0) and 4(T1), 12(T2), and 24(T3), weeks after treatment. RESULTS: Periodontal pocket depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP) in both groups showed significant improvements at the end of study compared to baseline. The reductions of PPD, CAL, and BOP in the Laser + NSPT group were significantly greater than NSPT group. At T3, the Laser + NSPT group had a mean PPD of 3.06 ± 0.86 mm, CAL of 2.58 ± 0.94 mm and BOP of 15.49%, while the NSPT group had a mean PPD of 4.46 ± 1.57 mm, CAL of 3.03 ± 1.25 mm and BOP of 64.29%. CONCLUSIONS: The diode laser as an adjunct to nonsurgical periodontal therapy may contribute to clinical outcomes for residual periodontal pockets. However, the approach may cause reduction of keratinized tissue width. TRIAL REGISTRATION NUMBER: This study was registered in the Chinese Clinical Trial Registry ChiCTR2200061194. CLINICAL RELEVANCE: Diode laser as an adjunct to nonsurgical periodontal therapy may contribute to the clinical outcomes for residual periodontal pockets in mandibular second molars.

miR-27a-5p alleviates periodontal inflammation by targeting phosphatase and tensin homolog deleted on chromosome ten.

INTRODUCTION: MicroRNAs (miRNAs), a type of non-coding RNA, have been demonstrated to be essential posttranscriptional modulators in oral diseases and inflammatory responses. However, the specific role of miR-27a-5p in periodontitis requires further investigation. In this study, we used both cellular and animal models to determine how miR-27a-5p affects the pathogenesis of periodontitis and its associated biological functions. METHODS: Quantitative real-time polymerase chain reaction and western blotting were used to analyze the expression of cytokines, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and miR-27a-5p transcription. Investigation of alveolar bone resorption and inflammation of the periodontium in ligature-induced periodontitis in mice was performed using micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, and tartrate-resistant acid phosphatase (TRAP) staining. The binding of miR-27a-5p and PTEN was predicted using the TargetScan database and experimentally confirmed using dual luciferase reporter gene assays. RESULTS: The inflamed gingiva showed lower levels of miR-27a-5p. Macrophages from miR-27a-5p-/- mice produced much higher quantities of pro-inflammatory cytokines owing to the stimulation of Porphyromonas gingivalis lipopolysaccharide, and miR-27a-5p-/- mice with ligature-induced periodontitis also exhibited more severe alveolar bone resorption and damage to the periodontium. Target validation assays identified PTEN as a direct target of bona. Blocking PTEN expression partially reduced inflammation, both in vitro and in vivo. CONCLUSIONS: miR-27a-5p alleviated the inflammatory response in periodontitis by targeting PTEN.

Co-Delivery of Daunorubicin and Homoharringtonine in Folic Acid Modified-Liposomes for Enhancing Therapeutic Effect on Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) remains a threatening disease due to severe complications, drug resistance, and high recurrence rates. Many drug combinations have demonstrated enhanced therapeutic effects in clinical practice. However, it requires complicated dosing regimens and is accompanied by increased toxicity. This study explored the combined effect of two therapeutic agents, daunorubicin (DNR) and homoharringtonine (HHT) in cell viability, apoptosis, and cell cycle in vitro and verified their synergistic effect. We encapsulated the two drugs into liposomes to construct a folic acid-modified co-delivery system (FA-DH-LP) to achieve an effective and safe therapeutic strategy. The FA-DH-LP was prepared by film hydration method. The resultant FA-DH-LP was homogeneously spherical and showed good blood compatibility with high encapsulation efficiency for DNR and HHT. The FA-DH-LP exhibited higher cellular uptake in HL60 and K562 cells and enhanced cytotoxicity than DNR/HHT co-delivery liposomes without folic acid modification (DH-LP) in vitro. In the HL60 subcutaneous xenotransplantation model, FA-DH-LP showed improved tumor targeting ability, anti-leukemia activity and safety profile superior to free combinational drugs and DH-LP after 18-day treatment. The results demonstrated that FA-DH-LP might present a promising delivery strategy to improve the efficacy of the two combinational chemotherapeutics while reducing toxicity.

Alantolactone inhibits oesophageal adenocarcinoma cells through nuclear factor erythroid 2-related factor 2-mediated reactive oxygen species increment.

BACKGROUND: Oesophageal adenocarcinoma (EAC) is a highly lethal cancer associated with a rapidly rising incidence and a poor prognosis. Alantolactone, a sesquiterpene lactone isolated from inula helenium, has anti-inflammatory, antimicrobial, neuroprotective activities, and anticancer properties. OBJECTIVE: In the present study, the anticancer effects of alantolactone on the human EAC cells were investigated in vitro and in vivo. METHODS AND FINDINGS: After treated with alantolactone, the cell viability of KYAE-1, KYAE-2, OE19, and OE33 cells reduced significantly compared with that of the control cells. Alantolactone induced apoptosis of the EAC cell lines by inhibiting the protein expression levels of nuclear factor erythroid2-related factor 2 (Nrf2). Furthermore, the apoptosis-inducing effect of alantolactone was enhanced by Nrf2 knockdown while reduced by overexpression of Nrf2. Antioxidant α-tocopherol and glutathione can protect EAC cell lines against alantolactone. A xenograft nude mice model showed that alantolactone can inhibit EAC growth in vivo. CONCLUSIONS: Alantolactone inhibits oesophageal adenocarcinoma cells through Nrf2-mediated reactive oxygen species (ROS) increment. Alantolactone maybe a potential therapeutical candidate for treating EAC.

Activating EGFR Signaling Attenuates Osteoarthritis Development Following Loading Injury in Mice.

Posttraumatic osteoarthritis (PTOA) results in joint pain, loss of joint function, and impaired quality of daily life in patients with limited treatment options. We previously demonstrated that epidermal growth factor receptor (EGFR) signaling is essential for maintaining chondroprogenitors during articular cartilage development and homeostasis. Here, we used a nonsurgical, loading-induced PTOA mouse model to investigate the protective action of EGFR signaling. A single bout of cyclic tibial loading at a peak force of 6 N injured cartilage at the posterior aspect of lateral femoral condyle. Similar loading at a peak force of 9 N ruptured the anterior cruciate ligament, causing additional cartilage damage at the medial compartment and ectopic cartilage formation in meniscus and synovium. Constitutively overexpression of an EGFR ligand, heparin binding EGF-like growth factor (HBEGF), in chondrocytes significantly reduced cartilage injury length, synovitis, and pain after 6 N loading and mitigated medial side cartilage damage and ectopic cartilage formation after 9 N loading. Mechanistically, overactivation of EGFR signaling protected chondrocytes from loading-induced apoptosis and loss of proliferative ability and lubricant synthesis. Overexpressing HBEGF in adult cartilage starting right before 6 N loading had similar beneficial effects. In contrast, inactivating EGFR in adult cartilage led to accelerated PTOA progression with elevated cartilage Mankin score and synovitis score and increased ectopic cartilage formation. As a therapeutic approach, we constructed a nanoparticle conjugated with the EGFR ligand TGFα. Intra-articular injections of this nanoconstruct once every 3 weeks for 12 weeks partially mitigated PTOA symptoms in cartilage and synovium after 6 N loading. Our findings demonstrate the anabolic actions of EGFR signaling in maintaining articular cartilage during PTOA development and shed light on developing a novel nanomedicine for PTOA. © 2022 American Society for Bone and Mineral Research (ASBMR).

Benzene, 1,2,4-Trimethoxy-5-(2-Methyl-1-Propen-1-yl), a New Neuroprotective Agent, Treats Intracerebral Hemorrhage by Inhibiting Apoptosis, Inflammation, and Oxidative Stress.

The highest disability rates and mortality among neurodegenerative diseases were caused by intracerebral hemorrhage (ICH). We previously proved that Benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) has an inhibitory effect on sodium ion channel and an activation effect on GABAA receptor, which were related to the brain injury. Based on this, we aimed to investigate BTY's neuroprotection on intracerebral hemorrhage and its underlying mechanism. In the in vivo study, a stereotactic injection of collagenase VII in Sprague Dawley rats (0.5 U) induced ICH and the BTY was intraperitoneally injected at 2 h after ICH. The neurological deficit scores, blood-brain barrier (BBB) permeability, and other indicators were assessed 24 h after ICH. The results showed that the BTY reduced brain edema and hematoma volume, improved neurological function and BBB permeability, and inhibited inflammatory factors and neuron apoptosis. The cell experiments proved that the BTY suppressed oxidative stress, cell apoptosis, intracellular calcium influx, and stabilized mitochondrial membrane potential by reducing glutamate's excitotoxicity. This study for the first time exhibited desirable neuroprotection of BTY, indicating it may be a promising neuroprotective agent for ICH therapy.

Salinity impact on the metabolic and taxonomic profiles of acid and alkali treated inoculum for hydrogen production from food waste.

This study evaluated the combined impact of salinity (2.5, 13, and 19.3 g NaCl/L) and inoculum pretreatment (acid/alkali) on the genomic and metabolic profiles of mesophilic fermentative bacteria for hydrogen (H2) production from food waste. Experimental results revealed that acid-treated inoculum showed the highest H2 yield (201.12 ± 13.84 mL H2/g of volatile solids added) under medium salinity levels compared to other experimental conditions. A 7-56% increase in H2 yield was observed for pretreated inoculum than untreated inoculum. Genomic analysis and metabolic pattern revealed that the H2 production was mainly through Clostridial-type fermentation under medium to high salinity levels, whereas Enterococcus-type fermentation under low salinity levels. Further, the genomic analysis uncovered that phyla Firmicutes (69.71-96.81%) and genus Clostridium sensu stricto 1 (33.28-94.04%) dominated during the exponential gas production phase. Overall, this study showed the significance of inoculum pretreatment for the bioconversion of food waste at different salinity levels.

A novel cone-beam CT scanning technique for measuring periodontal soft tissues in the esthetic area.

PURPOSE: This study investigated and tested a novel cone-beam computed tomography (CBCT) scanning technique capable of obtaining clear contours of soft tissues in the esthetic area. METHODS: Twenty-three periodontally healthy participants underwent this novel CBCT scanning technique. Soft tissue morphological parameters were measured on the CBCT images obtained. Intraoral clinical data were also collected at the same locations, and the accuracy of the CBCT method was tested. RESULTS: The median (interquartile range [IQR]) of the supracrestal gingival tissue thickness as 0.91 (0.73-1.13) mm, and the thickness of the central incisors was significantly greater than that of the canines (P < 0.05). The median (IQR) of keratinized tissue thickness was 0.73 (0.55-0.91) mm, which also showed a significantly greater thickness in the central incisors than in the canines (P < 0.05). Bland-Altman analysis suggested that CBCT could be accurate for measuring soft tissues in the esthetic area. CONCLUSION: The novel CBCT technique described yields clear contours of soft tissues in the esthetic area without the need for auxiliary tools. Moreover, measurements of soft tissue morphological parameters on CBCT appear to be accurate.

Effect of inoculum pretreatment on the microbial and metabolic dynamics of food waste dark fermentation.

This study systematically evaluated and compared different inoculum pretreatment methods to quickly select dark fermentative bacteria from anaerobic sludge for the bioconversion of food waste. The hydrogen (H2) production rate was found to be highest for 'heat + CO2' treated inoculum at 140.75 ± 2.61 mL/L/h compared to control experiments (60.27 ± 2.61 mL/L/h). At the same time, H2 yield was found to be highest for alkali-treated inoculum at 157.25 ± 7.62 mL/g of volatile solids (VS) added compared to control experiments (91.61 ± 1.93 mL/g VS). Analysis of organic acids suggests a Clostridial-type fermentation with acetate (0.52 to 1.60 g/L) and butyrate (1.69 to 2.42 g/L) being the major by-products. The microbial data analysis showed that Firmicutes (63.64-90.39%), Bacteroidota (1.16-21.88%), and Proteobacteria (2.09-9.93%) were dominant at the phylum level, whereas genus-level classification showed Clostridium sensu stricto 1 (6.37-42.63%), Streptococcus (1.87-28.96%), Prevotella (0.57-16.59%), and Enterococcus (0.56-14.51%) dominated under different experimental conditions.