Enhancement of bio-promoters on hexavalent chromium inhibited sulfur-driven denitrification: repairing damage, accelerating electron transfer, and reshaping microbial collaboration.

Proposing recovery strategies to recover heavy-metal-inhibited sulfur-driven denitrification, as well as disclosing recovery mechanisms, can provide technical support for the stable operation of bio-systems. This study proposed an effective bio-promoter (mediator-promoter composed of L-cysteine, biotin, cytokinin, and anthraquinone-2,6-disulfonate) to recover Cr(VI) inhibited sulfur-driven denitrification, which effectively reduced the recovery time of NO3--N reduction (18-21 cycles) and NO2--N reduction (27-42 cycles) compared with self-recovery. The mediator-promoter repaired microbial damage by promoting intracellular chromium efflux. Moreover, the mediator-promoter reduced the accumulated reactive oxygen species by stimulating the secretion of antioxidant enzymes, reaching equilibrium in the oxidative-antioxidant system. To improve electron transmission, the mediator-promoter restored S2O32- oxidation to provide adequate electron donors and increased electron transfer rate by increasing cytochrome c levels. Mediator-promoter boosted the abundance of Thiobacillus (sulfur-oxidizing bacterium) and Simplicispira (denitrifying bacterium), which were positively correlated, facilitating the rapid denitrification recovery and the long-term stable operation of recovered systems.

How halogenated aromatic compounds affect the electron supply and consumption in glucose supported denitrification?

Halogenated aromatic compounds possess bidirectional effects on denitrifying bio-electron behavior, providing electrons and potentially interfering with electron consumption. This study selected the typical 4-chlorophenol (4-CP, 0-100 mg/L) to explore its impact mechanism on glucose-supported denitrification. When COD(glucose)/COD(4-CP)=28.70-3.59, glucose metabolism remained the dominant electron supply process, although its removal efficiency decreased to 73.84-49.66 %. When COD(glucose)/COD(4-CP)=2.39-1.43, 4-CP changed microbial carbon metabolism priority by inhibiting the abundance of glucose metabolizing enzymes, gradually replacing glucose as the dominant electron donor. Moreover, 5-100 mg/L 4-CP reduced adenosine triphosphate (ATP) by 15.52-24.67 % and increased reactive oxygen species (ROS) by 31.13-63.47 %, causing severe lipid peroxidation, thus inhibiting the utilization efficiency of glucose. Activated by glucose, 4-CP dechlorination had stronger electron consumption ability than NO2--N reduction (NO3--N > 4-CP > NO2--N), combined with the decreased nirS and nirK genes abundance, resulting in NO2--N accumulation. Compared with the blank group (0 mg/L 4-CP), 5-40 mg/L and 60-100 mg/L 4-CP reduced the secretion of cytochrome c and flavin adenine dinucleotides (FAD), respectively, further decreasing the electron transfer activity of denitrification system. Micropruina, a genus that participated in denitrification based on glucose, was gradually replaced by Candidatus_Microthrix, a genus that possessed 4-CP degradation and denitrification functions after introducing 60-100 mg/L 4-CP.

Inhibitory mechanism of Cr(VI) on sulfur-based denitrification: Bio-toxicity, bio-electron characteristics, and microbial evolution.

Sulfur-based denitrification is a promising technology for efficient nitrogen removal in low-carbon wastewater, while it is easily affected by toxic substances. This study revealed the inhibitory mechanism of Cr(VI) on thiosulfate-based denitrification, including bio-toxicity and bio-electron characteristics response. The activity of nitrite reductase (NIR) was more sensitive to Cr(VI) than that of nitrate reductase (NAR), and NIR was inhibited by 21.32 % and 19.86 % under 5 and 10 mg/L Cr(VI), resulting in 10.12 and 15.62 mg/L of NO2--N accumulation. The biofilm intercepted 36.57 % of chromium extracellularly by increasing 25.78 % of extracellular polymeric substances, thereby protecting microbes from bio-toxicity under 5 mg/L Cr(VI). However, it was unable to resist 20-30 mg/L of Cr(VI) bio-toxicity as 19.95 and 14.29 mg Cr/(g volatile suspended solids) invaded intracellularly, inducing the accumulation of reactive oxygen species by 165.98 % and 169.12 %, which triggered microbial oxidative-stress and damaged the cells. In terms of electron transfer, S2O32- oxidation was inhibited, and parts of electrons were redirected intracellularly to maintain microbial activity, resulting in insufficient electron donors. Meanwhile, the contents of flavin adenine dinucleotide and cytochrome c decreased under 5-30 mg/L Cr(VI), reducing the electron acquisition rate of denitrification. Thermomonas (the dominant genus) possessed denitrification and Cr(VI) resistance abilities, playing an important role in antioxidant stress and biofilm formation. ENVIRONMENTAL IMPLICATION: Sulfur-based denitrification (SBD) is a promising method for nitrate removal in low-carbon wastewater, while toxic heavy metals such as Cr(VI) negatively impair denitrification. This study elucidated Cr(VI) inhibitory mechanisms on SBD, including bio-toxicity response, bio-electron characteristics, and microbial community structure. Higher concentrations Cr(VI) led to intracellular invasion and oxidative stress, evidenced by ROS accumulation. Moreover, Cr(VI) disrupted electron flow by inhibiting thiosulfate oxidation and affecting electron acquisition by denitrifying enzymes. This study provided valuable insights into Cr(VI) toxicity, which is of great significance for improving wastewater treatment technologies and maintaining efficient and stable operation of SBD in the face of complex environmental challenges.

New insights into N2O emission and electron competition under different chemical oxygen demand to nitrogen ratios in a biofilm system.

Nitrous oxide (N2O) is a greenhouse gas that could accumulate during the heterotrophic denitrification process. In this study, the effects of different chemical oxygen demand to nitrogen ratio (COD/N) on N2O production and electron competition was investigated. The electron competition was intensified with the decrease of electron supply, and Nos had the best electron competition ability. The model simulation results indicated that the degradation of NOx-Ns was a combination of diffusion and biological degradation. As reaction proceeding, N2O could accumulate inside biofilm. A thinner biofilm and a longer hydraulic retention time (HRT) might be an effective way to control N2O emission. The application of mathematical model is an opportunity to gain deep understanding of substrate degradation and electron competition inside biofilm.

Acidic Lysosome-Anchoring Croconium-Based Nanoplatform for Enhanced Triple-Mode Bioimaging and Fe3+-Triggered Tumor Synergistic Therapy.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

Examining the potential risk factors for variable airflow limitation in patients recovering from SARS-CoV-2 Omicron variant infection: A case-control study.

BACKGROUND: The Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. However, it remains uncertain whether variable airflow limitation (VAL) occurs during the recovery phase after contracting the Omicron variant. To address this question, we conducted a study to examine the occurrence of VAL in patients infected with the Omicron variant (BA.1) of SARS-CoV-2, and we also investigated the potential risk factors associated with this phenomenon. METHODS: We summarized and analyzed data taken from the electronic health records of recovering patients who had contracted the Omicron variant. The information was obtained from the Shuixi Branch of our Hospital during the period from January 22 to February 24, 2022. We focused on examining the occurrence of VAL and identifying the associated risk factors among these patients. RESULTS: In this case-control study, a total of 176 patients were enrolled. The occurrence of VAL was observed in 9.66% (17 individuals). Patients with VAL showed significantly elevated levels of the modified Borg dyspnea score, daytime cough score, night-time cough score, chest computed tomography severity score, and Treg ratio compared to those without VAL. Additionally, patients with VAL had a lower 6MWD value compared to those without it. Logistic regression analysis demonstrated that the modified Borg dyspnea score independently increased the risk of Omicron infection with VAL, with an odds ratio of 3.375, and a 95% confidence interval ranging from 1.537 to 7.408, with a P-value of .002. CONCLUSIONS: There is a possibility of experiencing VAL in certain patients recovering from the SARS-CoV-2 Omicron variant infection. The modified Borg dyspnea score has been identified as a standalone risk factor for the occurrence of VAL in SARS-CoV-2 Omicron infection.

Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia.

BACKGROUND: Intravenous and inhalation anesthesia are commonly used in the clinical setting. Recovery of cognitive function in elderly patients after surgery has received increased attention. In this study, the authors compared recovery of cognitive function in patients after different anesthesia techniques, and investigated which technique is safer. The authors also explored association between apolipoprotein E4 and postoperative cognitive dysfunction in patients undergoing general anesthesia. METHODS: A total of 2,000 patients were equally and randomly divided into intravenous and inhalation anesthesia groups. Total intravenous and inhalation anesthesia were used. Within 10 days after surgery, cognitive function was assessed daily using the Mini-Mental State Examination (MMSE). Restriction fragment length polymorphism of apolipoprotein E gene was analyzed. The primary outcome was MMSE score, frequency distribution of apolipoprotein E alleles and genotypes. P < 0.01 was used as statistically significant. RESULTS: MMSE score in inhalation preoperative baseline group significantly decreased at day 3 after surgery compared with the preoperational and intravenous anesthesia group. The proportion of patients scoring less than 25 points was significantly greater in the inhalation anesthesia group than in the intravenous anesthesia group at 3 days after surgery. In the inhalation anesthesia group, the decrease in MMSE score was closely related with apolipoprotein E ε4 allele. In the intravenous anesthesia group, the decrease in MMSE score was not correlated with apolipoprotein E ε4 allele. CONCLUSIONS: There was a strong association between the apolipoprotein E ε4 and postoperative cognitive dysfunction in elderly patients undergoing inhalation anesthetics.

Ocular manifestations of internal carotid artery dissection.

Internal carotid artery dissection (ICAD) results from disruption of the intima of the arterial wall, and can lead to intrusion of blood into the arterial wall and form an intramural hematoma. The hematoma can compress the true lumen of the vessel, causing functional stenosis or occlusion. The classic triad signs of ICAD include pain in the ipsilateral neck, head and orbital regions; a (partial) Horner syndrome; and cerebral or retinal ischemia. However, not all ICAD patients present with this classic signs. In some cases, ocular manifestations are the initial (and sometimes the only) findings. We summarize the ocular manifestations associated with ICAD in 3 categories: visual symptoms, oculosympathetic palsy, and ocular motor nerve palsy.

Schizandrin B inhibits the cis­DDP­induced apoptosis of HK­2 cells by activating ERK/NF­κB signaling to regulate the expression of survivin.

The nephrotoxicity of cisplatin limits its clinical application. Schizandrin B (SchB) has been demonstrated to have a variety of potential cytoprotective activities. The present study explored the molecular mechanisms by which SchB inhibits the dichlorodiammine platinum (DDP)­induced apoptosis of HK­2 proximal tubule epithelial cells. In vitro assays demonstrated that SchB increased the viability of HK­2 cells, alleviated the cis­DDP­induced activation of caspase­3, reduced apoptosis and improved the nuclear morphology of HK­2 cells. Additionally, the mechanism underlying the cis­DDP­induced apoptosis was indicated to involve the activation of p53, c­Jun­N­terminal kinase (JNK) and p38 signaling. Furthermore, SchB was demonstrated to activate extracellular signal­regulated kinase (ERK) and nuclear factor κB (NF­κB) signaling, and induce the expression of survivin. The inhibition of ERK and NF­κB signaling using U0126 and pyrollidine dithiocarbamate, respectively, inhibited the expression of survivin, whereas blocking the expression of survivin using small interfering RNA inhibited the alleviating effect of SchB on cis­DDP­induced apoptosis as indicated by a reduction in cleaved caspase­3 expression. In conclusion, SchB regulates ERK/NF­κB signaling to induce the expression of survivin, thereby alleviating cis­DDP­induced renal injury.

Establishment of a novel therapeutic vector targeting the trigeminal ganglion in rats.

BACKGROUND: In the pathogenesis of herpes simplex keratitis, herpes simplex virus type 1 (HSV-1) infection begins in corneal epithelium cells and then progresses through the sensory nerve endings and finally travels up forward to the trigeminal ganglion (TG), where it remains as latent virus. The available anti-HSV therapies do not completely suppress the recurrence of active HSV-1 infection. The aim of this study was to establish a novel replication-defective (rd) HSV-1 (rdHSV) vector (rdHSV-interferon gamma [IFNγ]) that could effectively target the TG. METHODS: Recombinant HSV-1 virus was inserted into a shuttle plasmid carrying IFNγ to establish the rdHSV-IFNγ vector. Safety was evaluated in vitro by 50% cellular cytotoxicity in transfected SH-SY5Y neuroblastoma cells and in vivo by Kaplan-Meier survival estimate and infection rate. Wistar rats were immunized with rdHSV-IFNγ to evaluate the TG targeting efficiency. Real-time polymerase chain reaction and Western blot assays were used to evaluate IFNγ mRNA and protein expression and rdHSV-IFNγ localization. RESULTS: The rdHSV-IFNγ vector was successfully constructed and showed high in vitro safety and overall survival and a corneal infection rate similar to that of control rats immunized with saline (control group; P>0.05). Real-time polymerase chain reaction and immunohistochemistry assays confirmed IFNγ expression and effective TG targeting on days 14 and 21, which increased with postimmunization time. Moreover, IFNγ was expressed sufficiently in the TG tissues. CONCLUSION: The rdHSV-IFNγ can act as an effective gene transporting vector that carries the therapeutic genes to the TG and triggers its expression.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits.

AIM: To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers. METHODS: New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3 groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B (n=5 each). The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28d after treatment. The corneas were examined with transmission electron microscopy (TEM) at 4wk. RESULTS: A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d (P<0.05). The corneal epithelium defect areas of the combined group was smaller than that of the CXL group (P<0.05) on 7 and 14d, but there were no statistical differences on 3, 21 and 28d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28d. The diameters of the corneal collagen fiber bundles (42.960±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group) were thicker than that of the control group (24.900±1.868 nm), but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION: CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.

Co-firing of levator palpebrae and masseter muscles links the masticatory and oculomotor system in humans.

Simultaneous co-firing of the levator palpebrae (LP) and pterygoid muscles were recorded in Marcus Gann Syndrome (MGS) patients in early clinical studies. "Release hypothesis" proposed an intrinsic masticatory oculomotor neural circuit and this kind circuit, which, however, has been observed only in amphibian. On the other hand, congenital miswiring hypothesis has overwhelmed other interpretations. However, the same phenomenon visualized in MGS cases was unveiled in human subjects without any sign of congenital oculomotor disorder. To further study co-firing of the upper eyelid and jaw muscles, we applied non-invasive EMG recording of the upper eyelid and ipsilateral masseter muscle belly in nine healthy volunteers. LP activity was determined initially by looking upward and active retraction of upper eyelid with head fixed. Then, dual channel inputs from upper eyelid and masseter muscle was recorded during tooth occlusion motivated by isometric masseter muscle contraction without jaw and face moving. The EMG recorded from upper eyelid when the subjects retracted eyelid with head fixed exhibited the same pattern as that collected during tooth occlusion, but the pattern was completely different from EMG of active eye closure. This reflects tooth occlusion evoked LP activity. Then, simultaneous co-firing of the LP and masseter muscle was recorded simultaneously during tooth occlusion without jaw movement. Finally, the aforementioned co-firing was recorded when the subjects conducted rhythmic occlusion and synchronous EMG from both muscles was acquired. In conclusions, humans may also have an intrinsic masticatory oculomotor circuit and release hypothesis may apply, at least, to some cases of MGS.

[Effects of Beauveria bassiana on Myzus persicae and its two predaceous natural enemies].

A Beauveria bassiana strain Bb21 was isolated from naturally infected green peach aphid Myzus persicae (Hemiptera: Aphididae). The effects of the strain on M. persicae and its two predaceous natural enemies Chrysoperla carnea (Neuroptera: Chrysopidae) and Harmonia axyridis (Coleoptera: Coccinellidae) were investigated under laboratory conditions. Bb21 had strong pathogenicity to M. persicae, with the LD50 of 97 conidia x mm(-2) (45-191, 95% confidence interval), but was less pathogenic to the second instar nymph of C. carnea, with the LD50 of 1089 conidia x mm(-2). The LD50 for C. carnea was 10.2 times higher than that for M. persicae. The pathogenicity of Bb21 to H. axyridis was very weak, with a low infection rate of 13% even at a high concentration 5 x 10(8) conidia x mL(-1). The Bb21 at low conidia concentration had less effect on the developmental period and fecundity of the two predaceous natural enemies. However, when applied at the high concentration 5 x 10(8) spores x mL(-1), Bb21 shortened the larval stage of H. axyridis averagely by 1.4 d and decreased the adult emergence rate and fecundity by 33% and 14%, respectively, and shortened the larval stage of C. carnea averagely by 0.7 d and decreased the adult emergence rate and fecundity by 24% and 11%, respectively. Since the LD50 for green peach aphid was much lower than that for the two predaceous natural enemies, and had very low effect on the adult emergence rate and fecundity of the two predators at the concentration recommended for field spray, Bb21 could be applied as a biocontrol agent of M. persicae in the integrated management of pernicious organisms.