Single-cell transcriptome analyses reveal critical regulators of spermatogonial stem cell fate transitions.

BACKGROUND: Spermatogonial stem cells (SSCs) are the foundation cells for continual spermatogenesis and germline regeneration in mammals. SSC activities reside in the undifferentiated spermatogonial population, and currently, the molecular identities of SSCs and their committed progenitors remain unclear. RESULTS: We performed single-cell transcriptome analysis on isolated undifferentiated spermatogonia from mice to decipher the molecular signatures of SSC fate transitions. Through comprehensive analysis, we delineated the developmental trajectory and identified candidate transcription factors (TFs) involved in the fate transitions of SSCs and their progenitors in distinct states. Specifically, we characterized the Asingle spermatogonial subtype marked by the expression of Eomes. Eomes+ cells contained enriched transplantable SSCs, and more than 90% of the cells remained in the quiescent state. Conditional deletion of Eomes in the germline did not impact steady-state spermatogenesis but enhanced SSC regeneration. Forced expression of Eomes in spermatogenic cells disrupted spermatogenesis mainly by affecting the cell cycle progression of undifferentiated spermatogonia. After injury, Eomes+ cells re-enter the cell cycle and divide to expand the SSC pool. Eomes+ cells consisted of 7 different subsets of cells at single-cell resolution, and genes enriched in glycolysis/gluconeogenesis and the PI3/Akt signaling pathway participated in the SSC regeneration process. CONCLUSIONS: In this study, we explored the molecular characteristics and critical regulators of subpopulations of undifferentiated spermatogonia. The findings of the present study described a quiescent SSC subpopulation, Eomes+ spermatogonia, and provided a dynamic transcriptional map of SSC fate determination.

Photoenzymatic CO2 Reduction Dominated by Collaborative Matching of Linkage and Linker in Covalent Organic Frameworks.

Artificial photoenzymatic systems based on covalent organic frameworks (COFs) provide an interesting platform for converting CO2 to value-added fuels. However, the dual roles of COFs as photocatalysts and enzyme hosts showcase contradictory preferences for structures, which poses a great challenge for their rational design. Herein, we report the collaborative matching of linkages and linkers in COFs on their ability to exert both photocatalytic activity and enzyme loading, which has been neglected until now. The linkage-dependent linker regulation pattern was elucidated, and the optimal match showed a record-breaking apparent quantum efficiency at 420 nm for photocatalytic cofactor regeneration of 13.95% with a high turnover frequency of 5.3 mmol g-1 h-1, outperforming other reported crystalline framework photocatalysts. Moreover, theoretical calculations and experiments revealed the mechanism underlying the effects of matching the linkage and linker on exciton dissociation and charge migration in photocatalysis. This newfound understanding enabled the construction of COFs with both high photoactivity and large pores closer in size to the formate dehydrogenase, achieving high loading capacity and a suitable confinement effect. Remarkably, the artificial photoenzymatic system constructed according to optimal linkage-linker matching exhibited highly efficient CO2 reduction, yielding formic acid with a specific activity as high as 1.46 mmol g-1 catalyst h-1 and good reusability, paving the way for sustainable CO2 conversion driven by visible light.

The silk gland proteome of Stenopsyche angustata provides insights into the underwater silk secretion.

Caddisworms (Trichoptera) spin adhesive silks to construct a variety of underwater composite structures. Many studies have focused on the fibroin heavy chain of caddisworm silk and found that it contains heavy phosphorylation to maintain a stable secondary structure. Besides fibroins, recent studies have also identified some new silk proteins within caddisworm silk. To better understand the silk composition and its secretion process, this study reports the silk gland proteome of a retreat-building caddisworm, Stenopsyche angustata Martynov (Trichoptera, Stenopsychidae). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), 2389 proteins were identified in the silk gland of S. angustata, among which 192 were predicted as secreted silk proteins. Twenty-nine proteins were found to be enriched in the front silk gland, whereas 109 proteins were enriched in the caudal silk gland. The fibroin heavy chain and nine uncharacterized silk proteins were identified as phosphorylated proteins. By analysing the sequence of the fibroin heavy chain, we found that it contains 13 Gly/Thr/Pro-rich regions, 12 Val/Ser/Arg-rich regions and a Gly/Arg/Thr-rich region. Three uncharacterized proteins were identified as sericin-like proteins due to their larger molecular weights, signal peptides and repetitive motifs rich in serine. This study provides valuable information for further clarifying the secretion and adhesion of underwater caddisworm silk.

A novel lncRNA-hidden polypeptide regulates malignant phenotypes and pemetrexed sensitivity in A549 pulmonary adenocarcinoma cells.

The advance of high-throughput sequencing enhances the discovery of short ORFs embedded in long non-coding RNAs (lncRNAs). Here, we uncovered the production and biological activity of lncRNA-hidden polypeptides in lung adenocarcinoma (LUAD). In the present study, bioinformatics was used to screen the lncRNA-hidden polypeptides in LUAD. Analysis of protein expression was done by western blot or immunofluorescence assay. The functions of the polypeptide were determined by detecting its effects on cell viability, proliferation, migration, invasion, and pemetrexed (PEM) sensitivity. The protein interactors of the polypeptide were analyzed by mass spectrometry after Co-immunoprecipitation (Co-IP) assay. The results showed that the lncRNA LINC00954 was confirmed to encode a novel polypeptide LINC00954-ORF. The polypeptide had tumor-suppressor features in A549 cells by repressing cell growth, motility and invasion. Moreover, the polypeptide enhanced PEM sensitivity and suppressed growth in A549/PEM cells. The protein interactors of this polypeptide had close correlations with RNA processing, amide metabolic process, translation, RNA binding, RNA transport, and DNA replication. As a conclusion, the LINC00954-ORF polypeptide embedded in lncRNA LINC00954 possesses tumor-suppressor features in A549 and PEM-resistant A549 cells and sensitizes PEM-resistant A549 cells to PEM, providing evidence that the LINC00954-ORF polypeptide is a potential anti-cancer agent in LUAD.

K4Cd3Ge4O13: A Congruent-Melting Germanate Nonlinear Optical Crystal with a Moderate Second-Harmonic Generation Intensity and Broad Transparent Window.

Mid-infrared (IR) nonlinear optical (NLO) materials have generated extensive research interest because of their crucial role in laser technology applications. Here, we report the synthesis of a novel cadmium germanate NLO crystal, K4Cd3Ge4O13, using spontaneous crystallization. K4Cd3Ge4O13 demonstrates a distinct three-dimensional structural framework characterized by twisted [Ge4O13] and [Cd3O10] clusters, composed of [GeO4], [CdO4], [CdO5], and [CdO6] basic building units, respectively, which represents an unprecedented structural feature. The title compound undergoes a desirable congruent melting behavior at about 727 °C. Notably, K4Cd3Ge4O13 demonstrates a short UV cutoff edge at 261 nm, coupled with a wide energy gap of 4.4 eV, and maintains an extended IR transparency window at around 6.0 µm. More importantly, it demonstrates a strong second-harmonic generation activity comparable to that of KH2PO4 (KDP) at 1064 nm. Theoretical analyses further elucidate that the remarkable optical performances of K4Cd3Ge4O13 are predominantly attributed to the cooperative effects of Ge-O and Cd-O bond-based motifs. These desired characteristics underscore the potential of K4Cd3Ge4O13 as a good candidate material for mid-IR NLO applications.

Activated Carbon Application Simultaneously Alleviates Paddy Soil Arsenic Mobilization and Carbon Emission by Decreasing Porewater Dissolved Organic Matter.

Flooding of paddy fields during the rice growing season enhances arsenic (As) mobilization and greenhouse gas (e.g., methane) emissions. In this study, an adsorbent for dissolved organic matter (DOM), namely, activated carbon (AC), was applied to an arsenic-contaminated paddy soil. The capacity for simultaneously alleviating soil carbon emissions and As accumulation in rice grains was explored. Soil microcosm incubations and 2-year pot experimental results indicated that AC amendment significantly decreased porewater DOM, Fe(III) reduction/Fe2+ release, and As release. More importantly, soil carbon dioxide and methane emissions were mitigated in anoxic microcosm incubations. Porewater DOM of pot experiments mainly consisted of humic-like fluorophores with a molecular structure of lignins and tannins, which could mediate microbial reduction of Fe(III) (oxyhydr)oxides. Soil microcosm incubation experiments cospiking with a carbon source and AC further consolidated that DOM electron shuttling and microbial carbon source functions were crucial for soil Fe(III) reduction, thus driving paddy soil As release and carbon emission. Additionally, the application of AC alleviated rice grain dimethylarsenate accumulation over 2 years. Our results highlight the importance of microbial extracellular electron transfer in driving paddy soil anaerobic respiration and decreasing porewater DOM in simultaneously remediating As contamination and mitigating methane emission in paddy fields.

Long-term Application of Agricultural Amendments Regulate Hydroxyl Radicals Production during Oxygenation of Paddy Soils.

Hydroxyl radicals (•OH) play a significant role in contaminant transformation and element cycling during redox fluctuations in paddy soil. However, these important processes might be affected by widely used agricultural amendments, such as urea, pig manure, and biochar, which have rarely been explored, especially regarding their impact on soil aggregates and associated biogeochemical processes. Herein, based on five years of fertilization experiments in the field, we found that agricultural amendments, especially coapplication of fertilizers and biochar, significantly increased soil organic carbon contents and the abundances of iron (Fe)-reducing bacteria. They also substantially altered the fraction of soil aggregates, which consequently enhanced the electron-donating capacity and the formation of active Fe(II) species (i.e., 0.5 M HCl-Fe(II)) in soil aggregates (0-2 mm), especially in small aggregates (0-3 µm). The highest contents of active Fe(II) species in small aggregates were mainly responsible for the highest •OH production (increased by 1.7-2.4-fold) and naphthalene attenuation in paddy soil with coapplication of fertilizers and biochar. Overall, this study offers new insights into the effects of agricultural amendments on regulating •OH formation in paddy soil and proposes feasible strategies for soil remediation in agricultural fields, especially in soils with frequent occurrences of redox fluctuations.

Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats.

Glutamatergic neurons in ventral pallidum (VPGlu) were recently reported to mediate motivational and emotional behavior, but its role in opioid addiction still remains to be elucidated. In this study we investigated the function of VPGlu in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm. By use of cell-type-specific fiber photometry, we showed that the calcium activity of VPGlu were inhibited during heroin self-administration and context-induced relapse, but activated after extinction in a new context. The drug seeking behavior was accompanied by the decreased calcium signal of VPGlu. Chemogenetic manipulation of VPGlu bidirectionally regulated heroin taking and seeking behavior. Anterograde tracing showed that the lateral habenula, one of the epithalamic structures, was the major output region of VPGlu, and its neuronal activity was consistent with VPGlu in different phases of heroin addiction and contributed to the motivation for heroin. VPGlu axon terminals in LHb exhibited dynamic activity in different phases of heroin addiction. Activation of VPGlu-LHb circuit reduced heroin seeking behavior during context-induced relapse. Furthermore, the balance of excitation/inhibition from VP to LHb was shifted to enhanced glutamate transmission after extinction of heroin seeking motivation. Overall, the present study demonstrated that the activity of VPGlu was involved in the regulation of heroin addiction and identified the VPGlu-LHb pathway as a potential intervention to reduce heroin seeking motivation.

Location Privacy Protection for the Internet of Things with Edge Computing Based on Clustering K-Anonymity.

With the development of the Internet of Things (IoT) and edge computing, more and more devices, such as sensor nodes and intelligent automated guided vehicles (AGVs), can serve as edge devices to provide Location-Based Services (LBS) through the IoT. As the number of applications increases, there is an abundance of sensitive information in the communication process, pushing the focus of privacy protection towards the communication process and edge devices. The challenge lies in the fact that most traditional location privacy protection algorithms are not suited for the IoT with edge computing, as they primarily focus on the security of remote servers. To enhance the capability of location privacy protection, this paper proposes a novel K-anonymity algorithm based on clustering. This novel algorithm incorporates a scheme that flexibly combines real and virtual locations based on the requirements of applications. Simulation results demonstrate that the proposed algorithm significantly improves location privacy protection for the IoT with edge computing. When compared to traditional K-anonymity algorithms, the proposed algorithm further enhances the security of location privacy by expanding the potential region in which the real node may be located, thereby limiting the effectiveness of "narrow-region" attacks.

Integrative chemical, physiological, and metabolomics analyses reveal nanospecific phytotoxicity of metal nanoparticles.

The increasing application of metal nanoparticles (NPs) via agrochemicals and sewage sludge results in non-negligible phytotoxicological risks. Herein, the potential phytotoxicity of ZnO and CuO NPs on wheat was determined using integrative chemical, physiological, and metabolomics analyses, in comparison to Zn2+ and Cu2+. It was found that ZnO or CuO NPs had a stronger inhibitory effect on wheat growth than Zn2+ or Cu2+. After exposure to ZnO or CuO NPs, wheat seedlings accumulated significantly higher levels of Zn or Cu than the corresponding Zn2+ or Cu2+ treatments, indicating the active uptake of NPs via wheat root. TEM analysis further confirmed the intake of NPs. Moreover, ZnO or CuO NPs exposure altered micronutrients (Fe, Mn, Cu, and Zn) accumulation in the tissues and decreased the activities of antioxidant enzymes. The metabolomics analysis identified 312, 357, 145, and 188 significantly changed metabolites (SCMs) in wheat root exposed to ZnO NPs, CuO NPs, Zn2+, and Cu2+, respectively. Most SCMs were nano-specific to ZnO (80%) and CuO NPs (58%), suggesting greater metabolic reprogramming by NPs than metal ions. Overall, nanospecific toxicity dominated the phytotoxicity of ZnO and CuO NPs, and our results provide a molecular perspective on the phytotoxicity of metal oxide NPs.

Clinical and genetic analysis of a case of O'Donnell-Luria-Rodan syndrome manifesting as growth retardation. / 以生长发育迟缓为表现的1例O'Donnell-Luria-Rodanç»¼åˆå¾ä¸´åºŠä¸Žé—ä¼ å­¦ç‰¹å¾åˆ†æž.

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E (lysine methyltransferase 2E) gene. The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation, intellectual disability, and distinctive facial features. Peripheral blood was collected from the patient, and DNA was extracted for genetic testing. Chromosome karyotyping showed 46XY. Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing (CNV-seq) revealed a 506 kb heterozygous deletion in the 7q22.3 region, which includes 6 genes, including KMT2E. The patient was diagnosed with ODLURO syndrome. Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results, indicating that this deletion was a de novo mutation. The clinical and genetic characteristics of this case can help increase clinicians' awareness of ODLURO syndrome.

Photocatalytic CO2 Reduction by Near-Infrared-Light (1200†nm) Irradiation and a Ruthenium-Intercalated NiAl-Layered Double Hydroxide.

Near-infrared light-driven photocatalytic CO2 reduction (NIR-CO2PR) holds tremendous promise for the production of valuable commodity chemicals and fuels. However, designing photocatalysts capable of reducing CO2 with low energy NIR photons remains challenging. Herein, a novel NIR-driven photocatalyst comprising an anionic Ru complex intercalated between NiAl-layered double hydroxide nanosheets (NiAl-Ru-LDH) is shown to deliver efficient CO2 photoreduction (0.887 µmol h-1) with CO selectivity of 84.81 % under 1200 nm illumination and excellent stability over 50 testing cycles. This remarkable performance results from the intercalated Ru complex lowering the LDH band gap (0.98 eV) via a compression-related charge redistribution phenomenon. Furthermore, transient absorption spectroscopy data verified light-induced electron transfer from the Ru complex towards the LDH sheets, increasing the availability of electrons to drive CO2PR. The presence of hydroxyl defects in the LDH sheets promotes the adsorption of CO2 molecules and lowers the energy barriers for NIR-CO2PR to CO. To our knowledge, this is one of the first reports of NIR-CO2PR at wavelengths up to 1200 nm in LDH-based photocatalyst systems.

Matched Kinetics Process Over Fe2O3-Co/NiO Heterostructure Enables Highly Efficient Nitrate Electroreduction to Ammonia.

Tandem nitrate electroreduction reaction (NO3 -RR) is a promising method for green ammonia (NH3) synthesis. However, the mismatched kinetics processes between NO3 --to-NO2 - and NO2 --to-NH3 results in poor selectivity for NH3 and excess NO2 - evolution in electrolyte solution. Herein, a Ni2+ substitution strategy for developing oxide heterostructure in Co/Fe layered double oxides (LDOs) was designed and employed as tandem electrocataltysts for NO3 -RR. (Co0.83Ni0.16)2Fe exhibited a high NH3 yield rate of 50.4 mg ⋅ cm-2 ⋅ h-1 with a Faradaic efficiency of 97.8 % at -0.42 V vs. reversible hydrogen electrode (RHE) in a pulsed electrolysis test. By combining with in situ/operando characterization technologies and theoretical calculations, we observed the strong selectivity of NH3 evolution over (Co0.83Ni0.16)2Fe, with Ni playing a dual role in NO3 -RR by i) modifying the electronic behavior of Co, and ii) serving as complementary site for active hydrogen (*H) supply. Therefore, the adsorption capacity of *NO2 and its subsequent hydrogenation on the Co sites became more thermodynamically feasible. This study shows that Ni substitution promotes the kinetics of the NO3 -RR and provides insights into the design of tandem electrocatalysts for NH3 evolution.

Guest-Stimulated Nonplanar Porphyrins in Flexible Metal-Organic Frameworks.

Nonplanar porphyrins with out-of-plane distortions play crucial roles in many biological functions and chemical applications. The artificial construction of nonplanar porphyrins usually involves organic synthesis and modification, which is a highly comprehensive approach. However, incorporating porphyrins into guest-stimulated flexible systems allows to manipulate the porphyrin distortion through simple ad/desorption of guest molecules. Here, a series of porphyrinic zirconium metal-organic frameworks (MOFs) is reported that exhibit guest-stimulated breathing behavior. X-Ray diffraction analysis and skeleton deviation plots confirm that the material suffers from porphyrin distortion to form a ruffled geometry under the desorption of guest molecules. Further investigation reveals that not only the degree of nonplanarity can be precisely manipulated but also the partial distortion of porphyrin in a single crystal grain can be readily achieved. As Lewis acidic catalyst, the MOF with nonplanar Co-porphyrin exhibits active properties in catalyzing CO2 /propylene oxide coupling reactions. This porphyrin distortion system provides a powerful tool for manipulating nonplanar porphyrins in MOFs with individual distortion profiles for various advanced applications.

Green and Rapid Synthesis of Acridine-Functionalized Covalent Organic Polymers for Photocatalysis by Combining Sonochemistry and Ion Induction.

Covalent organic polymers (COPs) are powerful candidates for achieving the visible-light-driven degradation of organic pollutants by virtue of structural designability, but their synthesis relies on harmful reagents and high temperatures, which weakens their associated green merits. Here, we report a novel strategy for combining sonochemistry with ion induction for the rapid preparation of acridine-functionalized COPs in green and mild aqueous solutions with tunable high yields of 80 to 90%. Photochemical studies reveal the ability of these COPs to harvest visible light and their sufficient conduction potentials for generating superoxide radicals. Furthermore, the photodegradation of methylene blue confirms the good photocatalytic activity and reusability of the zinc ion-based acridine-functionalized COP, which achieves 90.8% removal in 150 min and retains 82.5% activity after 5 reuse cycles, with a rate constant of up to 3.2 times that of commercial titanium dioxide nanoparticles. This strategy paves the way for the green, rapid, and mild synthesis of acridine-functionalized COPs, enabling visible light photocatalytic degradation for water treatment and energy conversion to advance in a thoroughly environmentally friendly and cost-effective manner.

Deep learning enables automatic adult age estimation based on CT reconstruction images of the costal cartilage.

OBJECTIVE: Adult age estimation (AAE) is a challenging task. Deep learning (DL) could be a supportive tool. This study aimed to develop DL models for AAE based on CT images and compare their performance to the manual visual scoring method. METHODS: Chest CT were reconstructed using volume rendering (VR) and maximum intensity projection (MIP) separately. Retrospective data of 2500 patients aged 20.00-69.99 years were obtained. The cohort was split into training (80%) and validation (20%) sets. Additional independent data from 200 patients were used as the test set and external validation set. Different modality DL models were developed accordingly. Comparisons were hierarchically performed by VR versus MIP, single-modality versus multi-modality, and DL versus manual method. Mean absolute error (MAE) was the primary parameter of comparison. RESULTS: A total of 2700 patients (mean age = 45.24 years ± 14.03 [SD]) were evaluated. Of single-modality models, MAEs yielded by VR were lower than MIP. Multi-modality models generally yielded lower MAEs than the optimal single-modality model. The best-performing multi-modality model obtained the lowest MAEs of 3.78 in males and 3.40 in females. On the test set, DL achieved MAEs of 3.78 in males and 3.92 in females, which were far better than the MAEs of 8.90 and 6.42 respectively, for the manual method. For the external validation, MAEs were 6.05 in males and 6.68 in females for DL, and 6.93 and 8.28 for the manual method. CONCLUSIONS: DL demonstrated better performance than the manual method in AAE based on CT reconstruction of the costal cartilage. CLINICAL RELEVANCE STATEMENT: Aging leads to diseases, functional performance deterioration, and both physical and physiological damage over time. Accurate AAE may aid in diagnosing the personalization of aging processes. KEY POINTS: • VR-based DL models outperformed MIP-based models with lower MAEs and higher R2 values. • All multi-modality DL models showed better performance than single-modality models in adult age estimation. • DL models achieved a better performance than expert assessments.

Analysis of the dynamic changes in gut microbiota in patients with different severity in sepsis.

BACKGROUND: The gastrointestinal tract contains a massive microbiota, and targeting the gut could be a potential intervention for sepsis. However, the interaction between sepsis and the intestinal microbiota is defined as an "incompletely understood bidirectional relationship". METHODS: This retrospective observational cohort study investigated the fecal microbiota of sepsis patients admitted to the Department of Critical Care Medicine of the Central Hospital of Wuhan, China, from May 2019 to January 2020. 14 septic patients were divided into the non-severe group and the severe group according to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Herein, fecal samples were serially collected on admission, the third, fourth, and fifth days, and ICU discharge. The fecal microbiota was analyzed by 16S rRNA gene sequencing and its correlation with clinical parameters was evaluated. RESULTS: Bacteroidetes, Firmicutes, and Proteobacteria were dominant phyla at ICU admission, and fecal biodiversity was not significantly different between the non-severe group (APACHE II < 15) and the severe group (APACHE II > 15). However, the diversity of the gut microbiota was significantly lower at ICU discharge than that at ICU admission with the extension of treatment time. Further significant difference flora analysis (LEfSe) showed that the genera Veillonella and Ruminococcus were the most discriminant biomarkers at ICU admission in non-severe and severe patients, respectively, while Enterococcus was the most discriminant biomarker at ICU discharge in all septic patients. Of note, liver function tests, including ALT, AST, TBIL, and DBIL correlated with the prevalence of various bacterial genera. CONCLUSIONS: The diversity of the gut microbiota in patients with sepsis decreases dramatically during ICU stay, and there are distinct dynamic changes in gut microbiota among patients with different severity in sepsis.

Coupling of Dissolved Organic Matter Molecular Fractionation with Iron and Sulfur Transformations during Sulfidation-Reoxidation Cycling.

Iron (oxyhydr)oxides and organic matter (OM) are intimately associated in natural environments, and their fate might be linked to sulfur during sulfidation-reoxidation cycling. However, the coupling of DOM molecular fractionation with Fe and S transformations following a full sulfidation-reoxidation cycle remains poorly understood. Here, we reacted Fh and Fh-OM associations with S(-II) anaerobically and then exposed the sulfidic systems to air. S(-II) preferentially reacted with Fh to form inorganic S (e.g., mackinawite, S0, and S22-) over being incorporated into OM as organic S and therefore indirectly affected OM fate by altering Fe speciation. Fh sulfidation was inhibited by associated OM, and the main secondary Fe species were mackinawite, Fe(II)-OM compounds, and lepidocrocite. Concomitantly, organic molecules high in unsaturation, aromaticity, and molecular weight were detached from solid-phase Fe species due to their lower affinities for secondary Fe species than for Fh. During the reoxidation stage, the previously formed Fe(II) species were reoxidized to Fh with a stronger aggregation, which recaptured formerly released OM with higher selectivity. Additionally, •OH was generated from Fe(II) oxygenation and degraded a portion of the DOM molecules. Overall, these results have significant implications for Fe, C, and S cycling in S-rich environments characterized by oscillating redox conditions.

Upregulation of dynorphin/kappa opioid receptor system in the dorsal hippocampus contributes to morphine withdrawal-induced place aversion.

Aversive emotion of opioid withdrawal generates motivational state leading to compulsive drug seeking and taking. Kappa opioid receptor (KOR) and its endogenous ligand dynorphin have been shown to participate in the regulation of aversive emotion. In the present study, we investigated the role of dynorphin/KOR system in the aversive emotion following opioid withdrawal in acute morphine-dependent mice. We found that blockade of KORs before pairing by intracerebroventricular injection of KOR antagonist norBNI (20, 40 µg) attenuated the development of morphine withdrawal-induced conditioned place aversion (CPA) behavior. We further found that morphine withdrawal increased dynorphin A expression in the dorsal hippocampus, but not in the amygdala, prefrontal cortex, nucleus accumbens, and thalamus. Microinjection of norBNI (20 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-induced CPA behavior. We further found that p38 MAPK was significantly activated in the dorsal hippocampus after morphine withdrawal, and the activation of p38 MAPK was blocked by pretreatment with norBNI. Accordingly, microinjection of p38 MAPK inhibitor SB203580 (5 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-produced CPA behavior. This study demonstrates that upregulation of dynorphin/KOR system in the dorsal hippocampus plays a critical role in the formation of aversive emotion associated with morphine withdrawal, suggesting that KOR antagonists may have therapeutic value for the treatment of opioid withdrawal-induced mood-related disorders.

Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine-induced cognitive impairment.

Chronic exposure to methamphetamine (METH) causes severe and persistent cognitive impairment. The present study aimed to investigate the role of dynorphin/κ opioid receptor (KOR) system in the development of METH-induced cognitive impairment. We found that mice showed significant cognitive impairment in the novel object recognition test (NOR) following daily injections of METH (10 mg/kg) for seven consecutive days. Systemic blockade of KOR prevented METH-induced cognitive impairment by pretreatment of the selective KOR antagonist norBNI (10 mg/kg, i.p.) or KOR deletion. Then, significant increased dynorphin and KOR mRNA were observed exclusively in prelimbic cortex (PL) other than infralimbic cortex. Finally, microinjection with norBNI into PL also improved cognitive memory in METH-treated mice using NOR and spontaneous alternation behaviour test. Our results demonstrated that dynorphin/KOR system activation in PL may be a possible mechanism for METH-induced cognitive impairment and shed light on KOR antagonists as a potential neuroprotective agent against the cognitive deficits induced by drug abuse.