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Background: Osteoprotegerin (OPG), an immunoregulatory member of the TNF receptor superfamily, is expressed in inflamed intestinal mucosa. We investigated whether OPG is produced by intestinal epithelial cells and tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the gene encoding OPG (TNFRSF11B) are associated with traveler's diarrhea (TD) among North American travelers to Mexico.Methods: OPG concentration was measured in the supernatants of T84 cells infected with various diarrheagenic Escherichia coli pathotypes. Genotyping was performed for 4 SNPs in the OPG gene for 968 North American travelers with or without TD. Stool samples from travelers with TD were evaluated for the presence of enteric pathogens.Results: T84 cells produced higher OPG levels in response to infection with various diarrheagenic E. coli pathotypes than with E. coli controls (P<.05). A SNP in the exon 1 region of the OPG gene (OPG+1181G>C) was associated with TD in white travelers who stayed in Mexico for >1 week during the summer (P=.009) and for TD due to nonsecretory pathogens (P=.001).Conclusions: Our study suggests that OPG is secreted by intestinal epithelial cells in response to enteropathogens and that a polymorphism in the OPG gene is associated with an increased susceptibility to TD. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is the most common pathogen identified in travelers to Mexico with diarrhea. There have been few recent studies looking at the etiology of diarrhea in travelers compared with the local resident population.Methods: We compared enteric pathogens isolated in two populations experiencing acute diarrhea acquired in Guadalajara, Mexico and also compared clinical illness caused by the principal pathogen, ETEC.Results: A single and 2 enteropathogens were detected in 107 (23%) and 8 (2%), respectively, of 457 Mexicans in 1995 and 1997, and 37 (29%) and 2 (2%), respectively, of 127 US adults in 1997. The most common pathogen was ETEC in both groups (11% of Mexican, 19% of US adults), although more common in the US travelers group (p =.0017). Shigella spp and Cryptosporidium spp were less common in the Mexican (<1% and <1%, respectively) than in the travelers group (6% and 3%, respectively) (p <.001 and p =.002, respectively). Entamoeba histolytica was more often found in the Mexican group (4% Mexican, 0% US adults; p =.027).Conclusion: ETEC is the most common pathogen among travelers and Mexican residents in this study. The duration of untreated diarrhea due to ETEC was significantly shorter among Mexicans (49 hours in Mexican, 94 hours in US adults; p =.0004), as was the average number of unformed stools passed over 4 days (Mexicans 8.8 versus travelers 17.9 stools; p =.0009 [ABSTRACT FROM AUTHOR]

OBJECTIVE: The Houston Department of Health and Human Services (HDHHS) has a centralized process for notifying and setting up follow-up appointments for women with abnormal Pap smears who are clients of HDHHS health centers. Faculty and a student from the University of Texas School of Public Health and HDHHS personnel jointly conducted a study to evaluate the process and performance of the system. METHODS: The study examined two subpopulations: women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions (ASCUS/LGSIL) and women with high-grade squamous intraepithelial lesions or atypical glandular cells of undetermined significance (HGSIL/AGCUS). A retrospective study was conducted of data on women attending eight HDHHS clinics during the period from February 1996 through August 2000. Records of 1,216 women referred for evaluation of abnormal Pap smears were reviewed. Process effectiveness was measured by the number of successful contacts made and the number of appointments set up. Performance was measured by compliance with referral appointments. Predictors included race/ethnicity, age, co-existence of a sexually transmitted disease, number of prior referrals, type of patient visit, and health center attended. RESULTS: HDHHS staff successfully notified 95.6% of women with ASCUS/LGSIL and 97.9% of women with HGSIL/AGCUS. Using performance criteria as outcome measures, high-risk women requiring targeted interventions were identified. Overall, 84.2% of women scheduled appointments. Among those with ASCUS/LGSIL, women identified as African American were 53% less likely to accept an appointment and 45% less likely to show up for the appointment than those identified as Hispanic or 'other.' Age and type of patient visit appeared to be significantly associated with patient compliance behavior. CONCLUSION: The study describes the effectiveness of a centralized patient follow-up process for women at risk for cervical cancer. [ABSTRACT FROM AUTHOR]

Maturation of peripheral hearing and auditory brainstem following perinatal asphyxia was investigated by longitudinal recording of brainstem auditory evoked potentials (BAEP) during the first year of life in affected infants. The general maturational course of the BAEP following asphyxia was similar to that in a control group of infants with normal births, although there were some abnormalities in the BAEP. Response threshold elevation seen in a few asphyxiated infants improved significantly during the first 3 months. The interpeak intervals in the asphyxiated infants did not differ significantly from that of the control-group infants except in the first month, when the I-V and III-V intervals were significantly prolonged in the severe asphyxia group. In contrast, wave V amplitude and V/I ratio were always smaller when compared to that of the control-group infants. Amplitude reduction of wave V was more sustained than the prolonged I-V interval. Persistent hearing loss and brainstem auditory impairment were seen in 6.8% and 14.6% of the asphyxiated infants, respectively. These findings suggest that asphyxia does not interfere significantly with the maturation of the auditory system in most asphyxiated infants and that sustained peripheral hearing loss and brainstem impairment occur only in a small proportion of affected infants. [ABSTRACT FROM AUTHOR]

It is unclear whether there is any postnatal abnormality in brainstem auditory function in late preterm small-for-gestational-age (SGA) infants. We investigated the functional integrity of the brainstem auditory pathway at 4 months after term in late preterm SGA infants and defined differences from appropriate-for-gestational age (AGA) infants. The maximum length sequence brainstem evoked response (MLS BAER) was recorded and analyzed in 24 SGA (birthweight < 3rd centile) infants and 28 AGA infants (birthweight > 10th centile). All infants were born at 33-36-week gestation without major perinatal and postnatal problems. We found that I-V interval in SGA infants was shorter than in AGA infants at higher click rates and significantly shorter at the highest rate of 910/s. Of the two smaller intervals, I-III interval was significantly shorter in SGA infants than in AGA infants at higher click rates of 455 and 910/s clicks, whereas III-V interval was similar in the two groups. The III-V/I-III interval ratio in SGA infants tended to be greater than in AGA infants at all rates and was significantly greater at 455 and 910/s clicks. The slope of I-III interval-rate functions in SGA infants was moderately smaller than in AGA infants.  Conclusions: The main and fundamental difference between late preterm SGA and AGA infants was a significant shortening in the MLS BAER I-III interval in SGA infants at higher click rates, suggesting moderately faster neural conduction in the caudal brainstem regions. Postnatal neural maturation in the caudal brainstem regions is moderately accelerated in late preterm SGA infants. What is Known: • At 40 weeks of postconceptional age, late preterm SGA infants manifested a mild delay in neural conduction in the auditory brainstem. What is New: • At 56 weeks of postconceptional age, late preterm SGA infants manifested moderately faster neural conduction in the caudal brainstem regions. • Postnatal neural maturation is moderately accelerated in the caudal brainstem regions of late preterm SGA infants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals ( P <0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA ( P <0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased ( P <0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged ( P >0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

Introduction: Although esophageal bronchogenic cysts are benign diseases, they may be accompanied by serious complications and have the possibility of recurrence. Therefore, once confirmed, it is necessary to treat the esophagobronchial cyst when the contraindication is excluded. Endoscopic treatment is usually used for lesions with small diameter and shallow origin, and has the advantages of small surgical trauma and risk, which can reduce the psychological burden of patients to a certain extent, help them to recover quickly, and lower hospital costs., Case Presentation: Case 1 is a 54-year-old Han Chinese man admitted to our hospital who complained of difficulty swallowing in the past 6 months. Case 2 is a 41-year-old Han Chinese man who was hospitalized in the past 3 months due to chest discomfort. Endoscopic ultrasound revealed a hypoechoic cystic lesion arising from the muscularis propria. Submucosal tunneling endoscopic resection was performed using a dual knife, and a cystic mass was observed between the mucosa and the muscular layers of the esophagus. On locating the cyst, an incision was made on the oral side of the lesion for evacuation. The cyst wall was excised using endoscopic argon plasma coagulation. We successfully removed the esophageal bronchogenic cyst lesion in the intrinsic muscle layer using submucosal tunneling endoscopic resection., Conclusion: Esophageal bronchogenic cysts are rare in clinical practice and lack specificity in clinical manifestations. Multiple methods can be used to determine the location and nature of the lesion and ultimately determine the treatment plan. Surgical resection and endoscopic treatment are two different treatment methods, and appropriate treatment plans need to be selected on the basis of the origin layer, size, and relationship with the esophagus of the lesion to reduce complications and improve prognosis., (© 2024. The Author(s).)

Aims: Very Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality., Methods: Fifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21‒91/s click rates., Results: Compared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and I‒V interpeak interval did not differ significantly between the two groups of infants. The I‒III interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the III‒V interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants., Conclusions: The main BAER abnormality in VLBW infants with CLD was a prolonged III‒V interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs., (© 2023. The Author(s).)

Objectives: To examine postnatal functional status of the brainstem auditory pathway in late preterm infants and detect any postnatal auditory abnormality., Methods: Thirty preterm infants born at 33-36 weeks gestation were studied three months after term. None had major perinatal and postnatal complications to minimize confounding effects. Brainstem auditory evoked responses were recorded with 21-91/s clicks., Results: Compared with postnatal age-matched normal term infants, the late preterm infants did not manifest any major abnormalities in brainstem auditory evoked responses at conventionally used 21/s clicks. At higher click rates, however, the late preterm infants manifested a moderate prolongation in BAER wave V latency. All interpeak intervals tended to be prolonged at higher click rates. The I-V interval was significantly prolonged at 51/s and particularly at 91/s clicks. Both the I-III and III-V intervals were significantly prolonged at 91/s. The late preterm infants also manifested reduced amplitudes of BAER waves III and V at most click rates., Conclusion: The central components of the brainstem auditory evoked responses were abnormal at higher click rates three months after term in the late preterm infants. Postnatal brainstem auditory function is suboptimal in late preterm infants without major complications. This suboptimal brainstem auditory function may not be clearly shown at term or an earlier stage, but can be shown later. Late preterm infants, although they may not have major complications, should be followed for later auditory development, providing valuable information for improving postnatal care., Competing Interests: Declaration of Competing Interest We have no potential conflicts of interest to be disclosed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Using maximum length sequence brainstem auditory evoked response (MLS BAER) to study brainstem neural conduction and maturation in fetal growth restriction (FGR) babies born very prematurely and assess the effect of FGR on brainstem neural maturation., Methods: MLS BAER was recorded and analyzed at a mean 40 week postmenstrual age in babies born at 27-32 week gestation without other major perinatal conditions or problems. The data were compared between babies with FGR (n = 30) and age-matched babies without FGR (n = 34) to define any differences., Results: A notable difference in MLS BAER was found in interpeak intervals between the babies with FGR and those without FGR. The FGR babies manifested significantly shortened I-III interval, moderately prolonged III-V interval, and significantly decreased III-V/I-III interval ratio. The slope of the I-III interval-rate function in FGR babies was moderately decreased, relative to that in the babies without FGR., Conclusion: FGR babies born very prematurely are associated with accelerated or precocial neural maturation at caudal brainstem regions, but moderately delayed maturation at rostral brainstem regions. The altered brainstem neural maturation is different from previously reported mildly delayed maturation in FGR babies born less prematurely, and may have important implication for neurodevelopmental outcome., Impact: This first MLS BAER study in FGR found that brainstem neural maturation in very premature FGR babies differed from age-matched non-FGR babies. Neural maturation in very premature FGR babies is accelerated or precocial at caudal brainstem regions but moderately delayed at rostral brainstem regions. The altered maturation is different from previously reported mild delay in brainstem neural maturation in FGR babies born less prematurely. FGR exerts a major and differential effect on brainstem neural maturation in babies born very prematurely. This alteration in very premature FGR babies may have important implication for their neurodevelopment., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16 S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium , which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8 + T cells, in the colon after FMT when compared with non-complete response patients ( n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.

Aims: Continuous positive airway pressure (CPAP) has been used for the prevention and treatment of neonatal respiratory distress for over four decades, but it remains very poorly understood whether there is any brainstem auditory abnormality in babies treated with CPAP. We aimed to detect brainstem auditory abnormality at 34-35 weeks of corrected age in preterm babies treated with CPAP and define any difference between different durations of CPAP treatment., Study Design: Preterm babies were recruited and dichotomized to those with CPAP treatment (CPAP group, n = 67) and those without CPAP treatment (n-CPAP group) (n = 49). Brainstem auditory evoked response (BAER) was studied at 34-35 weeks of corrected age., Results: Compared with the n-CPAP group, the CPAP group manifested moderately elevated BAER threshold and significantly prolonged latencies of BAER waves III and V and I-V interval. The prolongation was generally more significant in the babies with longer duration of CPAP treatment than those with shorter duration. The I-V interval in the babies with CPAP treatment for >30 days were significantly longer than those with fewer days of CPAP treatment., Conclusion: At 34-35 weeks of corrected age, preterm babies treated with CPAP are associated with moderate auditory abnormality. Further study is warranted to explore more detail of the auditory abnormality in babies treated with CPAP., Competing Interests: Conflict of interest We have no potential conflicts of interest to be disclosed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate postnatal neural conduction in the auditory brainstem in neonatal bronchopulmonary dysplasia (BPD) survivors., Methods: Thirty-two very preterm BPD survivors were studied at 57-58 weeks of postconceptional age. Brainstem auditory-evoked response was studied using maximum length sequence. Wave latencies and intervals were analyzed in detail. The controls were 37 normal term infants and 35 very preterm non-BPD infants., Results: Compared with normal term controls, BPD survivors showed significantly shortened I-III interval but significantly prolonged III-V interval and greater III-V/I-III interval ratio. Compared with very preterm non-BPD controls, BPD survivors showed a significant shortening in waves III latency and I-III interval, moderate prolonged III-V interval, and significantly greater III-V/I-III interval ratio. These differences were generally similar at all click rates used. The slopes of latency- and interval-click rate functions in BPD survivors did not differ significantly from the two control groups., Conclusions: Brainstem neural conduction in BPD survivors differed from normal term and age-matched non-BPD infants; neural maturation is accelerated in caudal brainstem regions but delayed in rostral regions. Neonatal BPD survivors are associated with differential maturation in neural conduction at caudal and rostral brainstem regions, which may constitute an important risk for postnatal neurodevelopment in BPD survivors., Impact: We found that brainstem neural conduction at PCA 57-58 weeks in neonatal BPD survivors differs from normal term and age-matched non-BPD infants. No major differences were found between normal term and very preterm non-BPD infants in brainstem auditory conduction. Neural conduction in BPD survivors is accelerated in caudal brainstem regions but delayed in rostral regions. Neonatal BPD survivors are associated with differential maturation in neural conduction at caudal and rostral brainstem regions. The abnormality may constitute an important risk for postnatal neurodevelopment in BPD survivors., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background and Purpose: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease., Methods: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total study duration 12 months)., Results: Fecal microbiota transplantation caused non-severe transient upper gastrointestinal symptoms. One subject receiving FMT was diagnosed with unrelated metastatic cancer and was removed from the trial. Beta diversity (taxa) of the microbiome, was similar comparing placebo and FMT groups at baseline, however, for subjects randomized to FMT, it increased significantly at 6 weeks ( p = 0.008) and 13 weeks ( p = 0.0008). After treatment with FMT, proportions of selective families within the phylum Firmicutes increased significantly, while proportion of microbiota belonging to Proteobacteria were significantly reduced. Objective motor findings showed only temporary improvement while subjective symptom improvements were reported compared to baseline in the group receiving FMT. Constipation, gut transient times (NS), and gut motility index ( p = 0.0374) were improved in the FMT group., Conclusions: Subjects with Parkinson's disease tolerated multi-dose-FMT, and experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms., Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT03671785., Competing Interests: HD and Z-DJ have applied for a patent for the FMT product used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 DuPont, Suescun, Jiang, Brown, Essigmann, Alexander, DuPont, Iqbal, Utay, Newmark and Schiess.)

Astaxanthin has high utilization value in functional food because of its strong antioxidant capacity. However, the astaxanthin content of Phaffia rhodozyma is relatively low. Adaptive laboratory evolution is an excellent method to obtain high-yield strains. TiO2 is a good inducer of oxidative stress. In this study, different concentrations of TiO2 were used to domesticate P. rhodozyma, and at a concentration of 1000 mg/L of TiO2 for 105 days, the optimal strain JMU-ALE105 for astaxanthin production was obtained. After fermentation, the astaxanthin content reached 6.50 mg/g, which was 41.61% higher than that of the original strain. The ALE105 strain was fermented by batch and fed-batch, and the astaxanthin content reached 6.81 mg/g. Transcriptomics analysis showed that the astaxanthin synthesis pathway, and fatty acid, pyruvate, and nitrogen metabolism pathway of the ALE105 strain were significantly upregulated. Based on the nitrogen metabolism pathway, the nitrogen source was adjusted by ammonium sulphate fed-batch fermentation, which increased the astaxanthin content, reaching 8.36 mg/g. This study provides a technical basis and theoretical research for promoting industrialization of astaxanthin production of P. rhodozyma., One-Sentence Summary: A high-yield astaxanthin strain (ALE105) was obtained through TiO2 domestication, and its metabolic mechanism was analysed by transcriptomics, which combined with nitrogen source regulation to further improve astaxanthin yield., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.)

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr -1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Parkinson's disease is a heterogeneous neurodegenerative disorder with distinctive gut microbiome patterns suggesting that interventions targeting the gut microbiota may prevent, slow, or reverse disease progression and severity., Objective: Because secretory IgA (SIgA) plays a key role in shaping the gut microbiota, characterization of the IgA-Biome of individuals classified into either the akinetic rigid (AR) or tremor dominant (TD) Parkinson's disease clinical subtypes was used to further define taxa unique to these distinct clinical phenotypes., Methods: Flow cytometry was used to separate IgA-coated and -uncoated bacteria from stool samples obtained from AR and TD patients followed by amplification and sequencing of the V4 region of the 16 S rDNA gene on the MiSeq platform (Illumina)., Results: IgA-Biome analyses identified significant alpha and beta diversity differences between the Parkinson's disease phenotypes and the Firmicutes/Bacteroides ratio was significantly higher in those with TD compared to those with AR. In addition, discriminant taxa analyses identified a more pro-inflammatory bacterial profile in the IgA+ fraction of those with the AR clinical subclass compared to IgA-Biome analyses of those with the TD subclass and with the taxa identified in the unsorted control samples., Conclusion: IgA-Biome analyses underscores the importance of the host immune response in shaping the gut microbiome potentially affecting disease progression and presentation. In the present study, IgA-Biome analyses identified a unique proinflammatory microbial signature in the IgA+ fraction of those with AR that would have otherwise been undetected using conventional microbiome analysis approaches.

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of the recipient microbiota did not mirror the donor stool taxa at either site, but an increase in the relative proportion of the genus Bacteroides as compared with Prevotella was noted in the stool post-transplant. FMTs may be a promising treatment option for recurrent multidrug-resistant infections.

IgA-coated bacteria in the gut (IgA-biome) provide a homeostatic function in healthy people through inhibition of microbial invaders and by protecting the epithelial monolayer of the gut. The laboratory methods used to detect this group of bacteria require flow cytometry and DNA sequencing (IgA-Seq). With dysbiosis (reduced diversity of the microbiome), the IgA-biome also is impaired. In the presence of enteric infection, oral vaccines, or an intestinal inflammatory disorder, the IgA-biome focuses on the pathogenic bacteria or foreign antigens, while in other chronic diseases associated with dysbiosis, the IgA-biome is reduced in capacity. Fecal microbiota transplantation (FMT), the use of fecal product from well-screened, healthy donors administered to patients with dysbiosis, has been successful in engrafting the intestine with healthy microbiota and metabolites leading to improve health. Through FMT, IgA-coated bacteria have been transferred to recipients retaining their immune coating. The IgA-biome should be evaluated in FMT studies as these mucosal-associated bacteria are more likely to be associated with successful transplantation than free luminal organisms. Studies of the microbiome pre- and post-FMT should employ metagenomic methods that identify bacteria at least at the species level to better identify organisms of interest while allowing comparisons of microbiota data between studies.

Objectives: To examine postnatal changes in the impaired brainstem auditory pathway in term infants after perinatal hypoxia-ischemia (HI)., Methods: Brainstem auditory evoked response (BAER) was studied at 2-4 months of age in term infants who suffered perinatal HI. The BAER data obtained at various click rates in these infants were compared with those in age-matched normal term controls to detect any abnormalities., Results: The infants after HI showed a slight elevation in BAER threshold. Four (9.8%) infants had threshold elevation. At 21/s clicks, there was a slight decrease in wave I latency, and a slight increase in wave III and V latencies. However, the I-V and I-III intervals in these infants were significantly increased ( p  < .05 and .05), whereas III-V interval was slightly increased. At higher click rates of 51 and 91/s, all BAER variables showed similar changes, with only small variations. An abnormal increase in the I-V and/or I-III intervals was seen in 4 (9.8%) infants, who were not associated with BAER threshold elevation., Conclusions: At 2-4 months of age, around 20% of the infants after perinatal HI showed a moderate degree of either peripheral or central impairment of the brainstem auditor pathway. Monitoring postnatal changes could provide valuable information for postnatal care of infants after perinatal HI.

Targeted muscle reinnervation (TMR) is a surgical procedure used to transfer residual peripheral nerves from amputated limbs to targeted muscles, which allows the target muscles to become sources of motor control information for function reconstruction. However, the effect of TMR on injured motor neurons is still unclear. In this study, we aimed to explore the effect of hind limb TMR surgery on injured motor neurons in the spinal cord of rats after tibial nerve transection. We found that the reduction in hind limb motor function and atrophy in mice caused by tibial nerve transection improved after TMR. TMR enhanced nerve regeneration by increasing the number of axons and myelin sheath thickness in the tibial nerve, increasing the number of anterior horn motor neurons, and increasing the number of choline acetyltransferase-positive cells and immunofluorescence intensity of synaptophysin in rat spinal cord. Our findings suggest that TMR may enable the reconnection of residual nerve fibers to target muscles, thus restoring hind limb motor function on the injured side., Competing Interests: None

The yeast Saccharomyces cerevisiae is effective in reducing the fishy malodor of sea products. However, the biotransformation pathways are still unclear. The seaweed B. fusco-purpurea was taken as an example to investigate the chemical transformation pathways for the deodorization process with S. cerevisiae fermentation. Sensory evaluation, GC-MS, GC-MS-O and odor activity value (OAV) analyses showed the fishy odorants were 1-octen-3-ol, (E)-2-nonenal, 2,4-decadienal, 2-pentylfuran, 2-octen-1-ol and nonanal. The removal of fishy malodor was related to the reactions of reduction, dehydrogenation, deformylation-oxygenation and ester syntheses via catalysis of aldehyde dehydrogenase, alcohol dehydrogenases, epoxide hydrolase, aldehyde deformylating-oxygenase, enone reductase, oxidases, dehydrogenases, aldo-keto reductases, ester synthase and acyltransferase. Interestingly, for the first time, it was found that 3,5-octadien-2-one transformed to 6-octen-2-one; and 2-pentylfuran transformed to o-cymene and hexyl acetate. Our findings enrich the knowledge for the removal of fishy malodor from sea products such as seaweeds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Vaccination is an important preventive measure against the coronavirus disease 19 (COVID-19) pandemic. We aimed to examine the willingness to vaccination and influencing factors among college students in China., Methods: From March 18 to April 26, 2021, we conducted a cross-sectional online survey among college students from 30 universities in Wuhan, Hubei Province, China. The survey was composed of the sociodemographic information, psychological status, experience during pandemic, the willingness of vaccination and related information. Students' attitudes towards vaccination were classified as 'vaccine acceptance', 'vaccine hesitancy', and 'vaccine resistance'. Multinomial logistic regression analyses were performed to identify the influencing factors associated with vaccine hesitancy and resistance., Results: Among 23,143 students who completed the survey, a total of 22,660 participants were included in the final analysis with an effective rate of 97.9% after excluding invalid questionnaires. A total of 60.6% of participants would be willing to receive COVID-19 vaccine, 33.4% were hesitant to vaccination, and 6.0% were resistant to vaccination. Social media platforms and government agencies were the main sources of information vaccination. Worry about the efficacy and adverse effects of vaccine were the top two common reason of vaccine hesitancy and resistance. Multiple multinomial logistic regression analysis identified that participants who worried about the adverse effects of vaccination were more likely to be vaccine hesitancy (aOR = 2.44, 95% CI = 2.30, 2.58) and resistance (aOR = 2.71, 95% CI = 2.40, 3.05)., Conclusion: More than half of college students are willing to receive the COVID-19 vaccine, whereas nearly one-third college students are still hesitant or resistant. It is crucial to provide sufficient and scientific information on the efficacy and safety of vaccine through social media and government agencies platforms to promote vaccine progress against COVID-19 and control the pandemic in China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Recent studies showed that neonatal necrotizing enterocolitis (NEC) adversely affects the brainstem auditory pathway in babies born at 30-40 week gestation. We compared the functional status of the pathway between babies born below 30 week gestation with NEC and those without NEC for any differences to understand whether NEC also affects the pathway in babies born at a smaller gestation., Method: Brainstem auditory evoked response was studied at term in NEC babies born below 30 week gestation. The data obtained were compared with age-matched non-NEC babies for any abnormalities, and then compared with previously reported NEC babies born at 30-34 week gestation for any differences., Results: Although the latencies of waves I and III did not differ significantly between NEC and non-NEC babies, wave V latency in NEC babies was longer than in non-NEC babies at all click rates used. In particular, I-V interpeak interval, reflecting brainstem conduction time, in NEC babies was significant longer than in non-NEC babies. Wave V amplitude and the V/I amplitude ratios in NEC babies was smaller than in non-NEC babies at some click rates. The I-V interval in our NEC babies born below 30 week gestation was longer than in previously reported NEC babies born at 30-34 week gestation at all click rates., Conclusion: NEC babies born below 30 week gestation are associated with delayed brainstem conduction time. Functional status of the brainstem auditory pathway in NEC babies born below 30 week gestation is less favorable than that in those with greater gestation., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Neon flying squid (OB) and jumbo squid (DG) mantles were evaluated to reveal the similarities and differences in their physicochemical features and protein abundances. Microstructural results indicated that the OB mantle exhibited numerous myofibril fragments and disordered microstructures after frozen storage compared with DG tissues. Chemical analysis suggested that freezing resulted in a rapid decrease in myofibrillar protein (MP) content, Ca 2+ -ATPase activity, and total sulfhydryl content, and promoted the increase in carbonyl content of MPs in both OB and DG. While, DG presented better MP stability than OB muscle after 120 days of frozen storage. Label-free proteomic analysis detected 24 down- and 33 up-regulated differentially abundant proteins (DAPs) in OB and DG mantles. Identified DAPs including isocitrate dehydrogenase and malic enzyme initiated a rapid decrease in the MP properties in OB samples. Moreover, DAPs were related to cytoskeleton function, including paramyosin, tropomyosin, and troponin C, which improved the stability of DG in response to freezing-induced changes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Stimuli-responsive solids with adjustable photophysical properties are particularly attractive because they can be used as smart materials in anticounterfeiting, information storage, holographic imaging, and other fields. Herein, we report a unique nonporous coordination polymer, {[Ag(3,3'-dpe)](2,2'-Hbpdc)} n ( 1 ; 3,3'-dpe = 1,2-dipyridin-3-ylethene and 2,2'-H 2 bpdc = 2,2'-biphenyldicarboxylic acid), that can convert to an extremely photoreactive compound, 1 ·H 2 O·MeCN (MeCN = acetonitrile), through guest capture. Upon irradiation of sunlight, 1 ·H 2 O·MeCN can transform to {[Ag(3,3'-tpcb) 0.5 ](2,2'-Hbpdc)(H 2 O)(MeCN)} n ( 2 ·H 2 O·MeCN; 3,3'-tpcb = 1,2,3,4-tetrapyridin-3-ylcyclobutane). 2 ·H 2 O·MeCN can lose its solvent molecules to form 2 and further return to 1 at high temperature. Accompanied by direct visualization based on multistep single-crystal-to-single-crystal conversions, the recyclable crystalline solid exhibits remarkable fluorescence changes, which makes it a supramolecular switch for application in multiple anticounterfeiting.

As we know, benign paroxysmal positional vertigo is a peripheral vestibular disorder,while vestibular migraine is a central vestibular disease. Although they are two different independent diseases, patients often choose to consult otolaryngology and neurology. The clinical manifestations of some patients with these two diseases are similar and the diagnosis is easy to be confused, but the treatment methods are completely different, and incorrect treatment methods will inevitably affect the curative effect and prognosis. Vestibular migraine is characterized by a diversity of clinical manifestations and signs, and the migraine symptoms of some patients do not match with the vestibular symptoms. There are 30% of vestibular migraine patients who showed isolated paroxysmal vertigo/dizziness and nystagmus, which is easily confused with benign paroxysmal positional vertigo and needs to be identified. Under the framework of the international classification of vestibular diseases, according to the new guideline of nystagmus examination and classification issued by Barany Association and new diagnostic criteria of two diseases, differential diagnosisof benign paroxysmal positional vertigo from vestibular migrainecan make up for one-sided understanding caused by the specialization of disciplines, improve thediagnosis and treatment of vestibular diseases, and thus reduce the misdiagnosis and mistreatment.

Background: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19., Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I 2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832)., Finding: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis., Interpretation: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations., Funding: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities., Competing Interests: The authors declare that they do not have any conflicts of interest (financial or otherwise)., (© 2021 The Author(s).)

Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline clinical data and risk factors related to rCDI and FMT were evaluated and compared between cancer types and between cases with remission and recurrence. Results: A total of 19 patients were studied: 12 with solid malignancies and 7 with hematologic malignancies. Most patients had stage IV cancer, and 21% of patients were in cancer remission. On average, patients had 2 episodes of CDI and received 3 courses of antibiotics within 1 year before FMT. 84% of patients with rCDI responded to FMT. Compared with patients who had CDI remission following FMT, non-remission cases were more likely to have received antibiotics following FMT. There were no serious adverse events or mortality within 30 days associated with FMT. Conclusions: FMT is safe, well-tolerated, and efficacious in treating rCDI in selected cancer patients. However, additional antibiotic use for complications from chemotherapy or immunosuppression negatively affected the efficacy of FMT in this population with advanced cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species- P. fragariae and P. rubi . Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that "transmit" exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. The study was aimed to understand the current situation of antibiotic resistance in Nanjing and to provide a reasonable basis for clinical selection of antibiotics to cure H. pylori., Objective: To investigate the current status of H. pylori antibiotics resistance in the Nanjing area, and analyze the primary and post-treatment antibiotic resistance of H. pylori in this area., Methods: During the period from July 2017 to December 2019, 1533 gastric mucosal specimens from patients with positive H. pylori confirmed by a breath test or rapid urease test were collected for isolation and identification of H. pylori. The agar dilution method was used for the antibiotic resistance test., Results: The result showed that the resistance rates of H. pylori to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 2.74%, 47.03%, 33.59%, 0.91%, 0.52% and 80.76%, respectively in the period of July 2017 to December 2019. The resistance rates of H. pylori (primary vs. post-treatment) to amoxicillin, clarithromycin, levofloxacin, furazolidone, tetracycline and metronidazole were 1.83% vs. 6.08%, 38.62% vs. 77.81%, 27.41% vs. 56.23%, 0.58% vs. 2.13%, 0.33% vs. 1.22%, 78.57% vs. 88.75%, respectively., Conclusion: Antibiotic resistance of H. pylori remained a problem for the effective eradication of this pathogen and its associated diseases in the Nanjing area. For post-treatment eradication patients, clinicians should take into account regional antibiotic resistance rate, personal antibiotic exposure history, economic benefit ratio, adverse antibiotic reactions, antibiotic availability and other aspects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis., Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured., Results: Median age at week 0 was 39 years, CD4 + T cell count 496 cells/mm 3 , HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution., Conclusions: Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560., Competing Interests: H.L.D. and Z-D.J. have applied for a patent for PRIM-DJ2727, and H.L.D. has received a grant from Rebiotix to study their FMT product. MF is an employee of Associates of Cape Cod, Inc., the manufacturer of the (1,3)-β-D-glucan test used in this study. No other authors have competing interests., (Copyright © Pathogens and Immunity 2020.)

Macroautophagy (autophagy) is driven by the coordinated actions of core autophagy-related (Atg) proteins. Atg8, the core Atg protein generally considered acting most downstream, has recently been shown to interact with other core Atg proteins via their Atg8-family-interacting motifs (AIMs). However, the extent, functional consequence, and evolutionary conservation of such interactions remain inadequately understood. Here, we show that, in the fission yeast Schizosaccharomyces pombe , Atg38, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex I, interacts with Atg8 via an AIM, which is highly conserved in Atg38 proteins of fission yeast species, but not conserved in Atg38 proteins of other species. This interaction recruits Atg38 to Atg8 on the phagophore assembly site (PAS) and consequently enhances PAS accumulation of the PtdIns3K complex I and Atg proteins acting downstream of the PtdIns3K complex I, including Atg8. The disruption of the Atg38-Atg8 interaction leads to the reduction of autophagosome size and autophagic flux. Remarkably, the loss of this interaction can be compensated by an artificial Atg14-Atg8 interaction. Our findings demonstrate that the Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to promote efficient autophagosome formation, underscore the prevalence and diversity of AIM-mediated connections within the autophagic machinery, and reveal unforeseen flexibility of such connections. Abbreviations : AIM: Atg8-family-interacting motif; AP-MS: affinity purification coupled with mass spectrometry; Atg: autophagy-related; FLIP: fluorescence loss in photobleaching; PAS: phagophore assembly site; PB: piggyBac ; PE: phosphatidylethanolamine; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate.