The stability of the Opi1p repressor for phospholipid biosynthetic gene expression in Saccharomyces cerevisiae is dependent on its interactions with Scs2p and Ino2p.

The yeast Saccharomyces cerevisiae Opi1p negatively regulates phospholipid biosynthetic genes. Under derepressing conditions, Opi1p binds to the endoplasmic reticulum/nuclear membrane with the aid of the membrane protein Scs2p and phosphatidic acids under derepressing conditions. Under repressing conditions, it enters the nucleus to inhibit the positive transcription factors Ino2p and Ino4p. While the spatial regulation of Opi1p is understood, the regulation of its abundance remains unclear. We investigated the role of Scs2p and Ino2p in Opi1p stability by overexpressing these proteins in yeast cells. Opi1p was stable in the presence of Scs2p, but mutations in residues required for interaction with Scs2p caused Opi1p unstable. Even in the absence of Scs2p, Opi1p remained stable in the strain having a mutation to increase phosphatidic acid levels. Conversely, overproduction of Ino2p reduced Opi1p stability, whereas a mutant Ino2p that cannot interact with Opi1p did not. Additionally, Opi1p was stable in strains lacking Ino2p or with a mutated Ino2p-binding domain. These findings suggest that regulation, adding another layer to the regulation of phospholipid biosynthetic gene expression by Opi1p.

Progress and Perspectives on Promising Covalent-Organic Frameworks (COFs) Materials for Energy Storage Capacity.

In recent years, a new class of highly crystalline advanced permeable materials covalent-organic frameworks (COFs) have garnered a great deal of attention thanks to their remarkable properties, such as their large surface area, highly ordered pores and channels, and controllable crystalline structures. The lower physical stability and electrical conductivity, however, prevent them from being widely used in applications like photocatalytic activities and innovative energy storage and conversion devices. For this reason, many studies have focused on finding ways to improve upon these interesting materials while also minimizing their drawbacks. This review article begins with a brief introduction to the history and major milestones of COFs development before moving on to a comprehensive exploration of the various synthesis methods and recent successes and signposts of their potential applications in carbon dioxide (CO2 ) sequestration, supercapacitors (SCs), lithium-ion batteries (LIBs), and hydrogen production (H2 -energy). In conclusion, the difficulties and potential of future developing with highly efficient COFs ideas for photocatalytic as well as electrochemical energy storage applications are highlighted.

Schwann cells transplantation improves nerve injury and alleviates neuropathic pain in rats.

The mechanism of neuropathic pain induced by nerve injury is complex and there are no effective treatment methods. P2X4 receptor expression is closely related to the occurrence of pain. Schwann cells (SCs) play a key protective role in the repair of peripheral nerve injury and myelin sheath regeneration. However, whether SCs can affect the expression of P2X4 receptor and play a role in pathological pain is still unclear. Therefore, this study investigated the effect of SCs on whether they can down regulate the expression of P2X4 receptor to affect pain. The results showed that in the neuropathic pain induced by sciatic nerve injury model, the expression of P2X4 receptor in spinal cord tissue was significantly increased and the pain sensation of rats was increased. While SCs transplantation could down regulate the expression of P2X4 receptors in spinal cord and increase the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats. These data indicate that SCs can reduce the expression of P2X4 receptors to alleviate neuropathic pain, indicating that SCs can mediate P2X4 receptor signalling as a new target for pain treatment.

The effects of exosomes originating from different cell sources on the differentiation of bone marrow mesenchymal stem cells into schwann cells.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. MATERIALS AND METHODS: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. RESULTS: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. CONCLUSIONS: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment.

Management of Post Dural Puncture Headache During Spinal Cord Stimulation Trials: A Review of Current Literature.

PURPOSE OF REVIEW: The purpose of this review is to evaluate, discuss and explain the current literature regarding management of post dural puncture headaches (PDPH) during spinal cord stimulation (SCS) trials. RECENT FINDINGS: Although an epidural blood patch (EBP) remains the gold standard in treatment of PDPH, current literature describes other modalities including various peripheral nerve blocks and pharmacological treatments to reduce PDPH symptoms. PDPH management in SCS centers around conservative treatment and EBP. It has been shown that some practitioners choose prophylactic measures and/or an EBP at the time of the lead placement. Recent literature regarding obstetric anesthesia related PDPH management has included newer potential modalities for addressing symptom improvement that can also be applied to PDPH from SCS trial dural punctures. Due to limited data overall, further studies are needed to effectively provide a guideline on optimal treatment protocols for PDPH after dural puncture in SCS trials.

Cervical Spinal Cord Stimulation for Failed Neck Surgery Syndrome.

PURPOSE OF REVIEW: Cervical spine pain with or without radicular symptoms is a common condition leading to high utilization of the healthcare system with over 10 million medical visits per year. Many patients undergo surgical interventions and unfortunately are still left with neck and upper extremity pain, sometimes referred to as "Failed Neck Surgery Syndrome." When these options fail, cervical spinal cord stimulation can be a useful tool to decrease pain and suffering as well as reduce prescription medication use. RECENT FINDINGS: Spinal cord stimulation is a well-established therapy for chronic back and leg pain and is becoming more popular for neck and upper extremity pain. Recent studies have explored cervical spinal cord stimulation with successful outcomes regarding improved pain scores, functional outcomes, and reduction of prescription medication use. Continued research into cervical spinal cord stimulation is essential for maximizing its therapeutic potential for patients with chronic neck and upper extremity pain. This review highlights the importance of cervical spinal cord stimulation as an option for patients with failed neck surgery syndrome.

Defining Short- and Long-Term Programming Requirements in Patients Treated With 10-kHz Spinal Cord Stimulation.

OBJECTIVES: High-frequency spinal cord stimulation (10-kHz SCS) has been shown to be an effective treatment for refractory low back pain and neck pain with and without limb pain in clinical trial and real-world studies. However, limited information is available in the literature on the type and frequency of programming parameters required to optimize pain relief. MATERIALS AND METHODS: Retrospective trial and postimplant clinical and system device data were analyzed from consecutive patients with neck pain and low back pain, with and without limb pain, from a single clinical site, including both thoracic and cervical lead placement. Best bipole, stimulation parameters, and outcomes, including pain relief, change in opioid medication use, sleep, and daily function, were analyzed. RESULTS: Of the 92 patients in the trial, 70 received a permanent implant. Of these, the mean duration of follow-up was 1.8 ± 1.3 years. Pain relief of ≥50% at the last follow-up was achieved by 64% of patients implanted; in addition, 65% reduced their opioid medication use; 65% reported improved sleep, and 71% reported improved function. There was some consistency between the "best" bipole at trial and permanent implant, with 82% of patients within one bipole location, including 54% of permanent implants who were using the same best bipole as at trial. After permanent implant, device reprogramming was minimal, with ≤one reprogramming change per patient per quarter required to maintain pain outcomes. CONCLUSIONS: In the study, 10-kHz SCS was an effective therapy for treating chronic pain, whereby a high responder rate (≥50% pain relief) was achieved with short time to pain relief in trial and maintained with limited device programming after permanent implant. The data presented here provide insight into the programming required during the trial and implant stages to obtain and maintain therapeutic efficacy.

Examining the Duration of Carryover Effect in Patients With Chronic Pain Treated With Spinal Cord Stimulation (EChO Study): An Open, Interventional, Investigator-Initiated, International Multicenter Study.

OBJECTIVES: Spinal cord stimulation (SCS) is a surgical treatment for severe, chronic, neuropathic pain. It is based on one to two lead(s) implanted in the epidural space, stimulating the dorsal column. It has long been assumed that when deactivating SCS, there is a variable interval before the patient perceives the return of the pain, a phenomenon often termed echo or carryover effect. Although the carryover effect has been problematized as a source of error in crossover studies, no experimental investigation of the effect has been published. This open, prospective, international multicenter study aimed to systematically document, quantify, and investigate the carryover effect in SCS. MATERIALS AND METHODS: Eligible patients with a beneficial effect from their SCS treatment were instructed to deactivate their SCS device in a home setting and to reactivate it when their pain returned. The primary outcome was duration of carryover time defined as the time interval from deactivation to reactivation. Central clinical parameters (age, sex, indication for SCS, SCS treatment details, pain score) were registered and correlated with carryover time using nonparametric tests (Mann-Whitney/Kruskal-Wallis) for categorical data and linear regression for continuous data. RESULTS: In total, 158 patients were included in the analyses. A median carryover time of five hours was found (interquartile range 2.5;21 hours). Back pain as primary indication for SCS, high-frequency stimulation, and higher pain score at the time of deactivation were correlated with longer carryover time. CONCLUSIONS: This study confirms the existence of the carryover effect and indicates a remarkably high degree of interindividual variation. The results suggest that the magnitude of carryover may be correlated to the nature of the pain condition and possibly stimulation paradigms. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03386058.

Defining the Boundaries of Patient Perception in Spinal Cord Stimulation Programming.

OBJECTIVES: Recent developments in spinal cord stimulation (SCS) programming have initiated new modalities of imperceptible stimulation. However, the boundaries of sensory perception are not well defined. The BEnchtop NEuromodulation Following endIng of Trial study aimed to create a map of perceptual threshold responses across a broad range of SCS parameters and programming to inform subperception therapy design. MATERIALS AND METHODS: This multicenter study was conducted at seven US sites. A total of 43 patients with low back and/or leg pain who completed a percutaneous commercial SCS trial were enrolled. Test stimulation was delivered through trial leads for approximately 90 minutes before removal. SCS parameters, including amplitude, frequency, pulse width (PW), electrode configuration, cycling, and multifrequency stimulation were varied during testing. Paresthesia threshold (PT), comfort level (CL), perceptual coverage area, and paresthesia quality (through patient selection of keywords) were collected. Differences were evaluated with analysis of variance followed by post hoc multiple comparisons using t-tests with Bonferroni correction. RESULTS: PT was primarily determined by PW and was insensitive to frequency for constant frequency stimulation (range: 20 Hz-10 kHz; F(1284) = 69.58, p < 0.0001). For all tests, CL was approximately 25% higher than PT. The dominant variable that influenced paresthesia quality was frequency. Sensations described as comfortable and tingling were most common for frequencies between 60 Hz and 2.4 kHz; unpleasant sensations were generally more common outside this range. Increasing distance between active electrodes from 7 mm to 14 mm, or cycling the SCS waveform at 1 Hz, decreased PT (p < 0.0001). Finally, PT for a low-frequency stimulus (ie, 60 Hz) was unaffected by mixing with a sub-PT high-frequency stimulus. CONCLUSIONS: In contrast to previous work investigating narrower ranges, PW primarily influenced PT, independently of frequency. Paresthesia quality was primarily influenced by pulse frequency. These findings advance our understanding of SCS therapy and may be used to improve future novel neuromodulation paradigms.

Ninety-Hz Spinal Cord Stimulation-Induced Analgesia Is Dependent on Active Charge Balance and Is Nonlinearly Related to Amplitude: A Sham-Controlled Behavioral Study in a Rodent Model of Chronic Neuropathic Pain.

BACKGROUND: Ninety-Hz active-recharge spinal cord stimulation (SCS) applied at below sensory-threshold intensity, as used with fast-acting subperception therapy spinal cord stimulation, has been shown clinically to produce significant analgesia, but additional characterization is required to better understand the therapy. This preclinical study investigates the behavioral effect of multiple 90-Hz SCS variants in a rodent model of neuropathic pain, focusing on charge balance and the relationship between 90-Hz efficacy and stimulation intensity. MATERIALS AND METHODS: Rats (n = 24) received a unilateral partial sciatic nerve ligation to induce neuropathic pain and were implanted with a quadripolar lead at T13. Mechanical hypersensitivity was assessed before, during, and after 60 minutes of SCS. After a prescreen with 50-Hz SCS 67% motor threshold ([MT], the positive control), rats underwent a randomized-crossover study including sham SCS and several 90-Hz SCS paradigms (at 40% MT or 60% MT, either using active or pseudopassive recharge) (experiment 1, n = 16). A second, identical experiment (experiment 2) was performed to supplement data with 90-Hz SCS at 20% and 80% MT (experiment 2, n = 8). RESULTS: Experiment 1: At 40% MT, 90-Hz active-recharge SCS produced a significantly larger recovery to baseline than did 90-Hz pseudopassive SCS at both tested intensities and sham SCS. Experiment 2: Only the 90-Hz SCS active recharge at 40% MT and 50-Hz SCS positive control caused mean recovery to baseline that was statistically better than that of sham SCS. CONCLUSIONS: The degree to which 90-Hz SCS reduced mechanical hypersensitivity during stimulation depended on the nature of charge balance, with 90-Hz active-recharge SCS generating better responses than did 90-Hz pseudopassive recharge SCS. In addition, our findings suggest that the amplitude of 90-Hz active-recharge SCS must be carefully configured for efficacy.

Weight Trends After Spinal Cord Stimulation Therapy for Chronic Pain.

OBJECTIVES: Spinal cord stimulation (SCS) therapy is an effective treatment for chronic pain, particularly in conditions such as postlaminectomy syndrome and complex regional pain syndrome (CRPS). Rare case reports described significant weight loss in patients who underwent dorsal column SCS therapy for chronic pain. Recently, neuromodulation for obesity has become a novel field for research. We aimed to investigate weight trends among patients treated with SCS for chronic pain. MATERIALS AND METHODS: We conducted a retrospective chart review in 342 patients treated with SCS or dorsal root ganglion stimulators at our institution between 2010 and 2023. Patients had their weight recorded before SCS implantation and at least once within 12 months after surgery. We also conducted interviews with 28 patients who experienced significant weight loss or had revision procedures owing to weight loss. RESULTS: We found that 105 of 342 patients (30.7%) experienced weight loss of ≥5% within a year of implantation, and 32 of 105 (30.5%, 9.4% of all patients) experienced weight loss of ≥ 10%. A multivariate regression analysis revealed a modest increase in the likelihood of weight loss among patients with CRPS (odds ratio [OR] = 1.17, 95% CI [1.04, 1.30], p = 0.007) and in those who achieved pain relief after implantation (OR = 1.22, 95% CI [1.05,1.40], p = 0.008). Of the 28 patients with significant weight loss who were interviewed, 12 (43%) could not explain the reasons for their weight loss, whereas eight (29%) reported decreased appetite. Leads placed at higher thoracic levels were associated with increased rates of weight loss (37.2% at T6-T8 and 22.3% at T8-T10; p = 0.038). CONCLUSIONS: Our findings suggest that SCS therapy may affect weight in patients with chronic pain. Further studies are needed to investigate the potential role of SCS in weight modulation.

The Effect of Spinal Cord Stimulation on Spinal Dorsal Horn Lipid Expression in Experimental Painful Diabetic Polyneuropathy: A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Imaging Study.

OBJECTIVES: Diabetes-induced peripheral nerve fiber damage can cause painful diabetic polyneuropathy (PDPN), induced by central sensitization through proinflammatory processes in the spinal dorsal horn. Disturbances in spinal dorsal horn lipid metabolism play a major role in proinflammatory regulation. Conventional (Con)-spinal cord stimulation (SCS) is an alternative treatment for pain relief in PDPN, whereas differential target multiplexed (DTM)-SCS could be more effective than Con-SCS, specifically targeting the spinal inflammatory response. We hypothesize that Con- and DTM-SCS differentially affect lipid metabolism in the spinal cord of PDPN animals. To study pain relief mechanisms, we analyzed lipid expression in the spinal dorsal horn using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry imaging (MSI). MATERIAL AND METHODS: Diabetes was induced through streptozotocin (STZ) injection in 28 rats, of which 12 developed PDPN. These and four nondiabetic animals (sham STZ) were implanted with a quadripolar lead and stimulated with Con-, DTM-, or Sham-SCS for 48 hours. Mechanical sensitivity was assessed using Von Frey filaments after 24 and 48 hours. After 48 hours of SCS, the spinal cord was collected, and lipids were analyzed using MALDI-TOF MSI. RESULTS: STZ-induced hypersensitivity in the hind paws was reduced by Con- and DTM-SCS. PDPN induction decreased the expression of a glycosphingolipid in laminae 3 of the spinal dorsal horn. After 48 hours of Con- and DTM-SCS, expression levels of several lipids in the spinal dorsal horn decreased, including (HexCer 36:1;O, 40:1;O3), diacylglycerophosphocholines (PC 36:1, 38:6, 40:5), and diacylglycerophosphoserines (PS 36:4). CONCLUSIONS: Both Con- and DTM-SCS provide pain relief and decrease spinal dorsal horn lipid expression of PDPN animals, highlighting the complex effects of SCS on the spinal cord physiology. STZ-induced PDPN has a limited effect on lipid expression in the spinal dorsal horn.

Effect of Neurostimulation on Chronic Pancreatic Pain: A Systematic Review.

BACKGROUND: Chronic pancreatic pain is one of the most severe causes of visceral pain, and treatment response is often limited. Neurostimulation techniques have been investigated for chronic pain syndromes once there are pathophysiological reasons to believe that these methods activate descending pain inhibitory systems. Considering this, we designed this systematic literature review to investigate the evidence on neuromodulation techniques as a treatment for chronic pancreatic pain. MATERIALS AND METHODS: We performed a literature search using the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase until April 2024. The included studies used neurostimulation techniques in participants with chronic pancreatic pain and reported pain-related outcomes, with a focus on pain scales and opioid intake. Two reviewers screened and extracted data, and a third reviewer resolved discrepancies. We assessed the risk of bias using the Jadad scale. The authors then grouped the findings by the target of the neurostimulation, cortex, spinal cord, or peripheral nerves; described the findings qualitatively in the results section, including qualitative data reported by the articles; and calculated effect sizes of pain-related outcomes. RESULTS: A total of 22 studies were included (7 randomized clinical trials [RCTs], 14 case series, and 1 survey), including a total of 257 clinical trial participants. The two outcomes most commonly reported were pain, measured by the visual analogue scale (VAS), numeric rating scale (NRS), and pressure pain threshold scores, and opioid intake. Two RCTs investigated repetitive transcranial magnetic stimulation (rTMS), showing a reduction of 36% (±16) (d = 2.25; 95% CI, 0.66-3.83) and 27.2% (±24.5%) (d = 2.594; 95% CI, 1.303-3.885) in VAS pain scale. In another clinical trial, transcranial direct-current stimulation (tDCS) and transcranial pulsed current stimulation were not observed to effect a significant reduction in VAS pain (χ2 = 5.87; p = 0.12). However, a complete remission was reported in one tDCS case. Spinal cord stimulation (SCS) and dorsal root ganglion stimulation were performed in a survey and 11 case series, showing major pain decrease and diminished opioid use in 90% of participants after successful implantation; most studies had follow-up periods of months to years. Two noninvasive vagal nerve stimulation (VNS) RCTs showed no significant pain reduction in pain thresholds or VAS (d = 0.916; 95% CI, -0.005 to 1.838; and d = 0.17; -0.86 to 1.20; p = 0.72; respectively). Splanchnic nerve stimulation in one case report showed complete pain reduction accompanied by discontinuation of oral morphine and fentanyl lozenges and a 95% decrease in fentanyl patch use. Two RCTs investigated transcutaneous electrical nerve stimulation (TENS). One found a significant pain reduction effect with the NRS (d = 1.481; 95% CI, 1.82-1.143), and decreased opioid use, while the other RCT did not show significant benefit. Additionally, one case report with TENS showed pain improvement that was not quantitatively measured. DISCUSSION: The neuromodulation techniques of rTMS and SCS showed the most consistent potential as a treatment method for chronic pancreatic pain. However, the studies have notable limitations, and SCS has had no clinical trials. For VNS, we have two RCTs that showed a non-statistically significant improvement; we believe that both studies had a lack of power issue and suggest a gap in the literature for new RCTs exploring this modality. Additionally, tDCS and TENS showed mixed results. Another important insight was that opioid intake decrease is a common trend among most studies included and that adverse effects were rarely reported. To further elucidate the potential of these neurostimulation techniques, we suggest the development of new clinical trials with larger samples and adequate sham controls.

Evaluating the Effects of Kidney Preservation at 10 °C with Hemopure and Sodium Thiosulfate in a Rat Model of Syngeneic Orthotopic Kidney Transplantation.

Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia-reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia-reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.

Effect of Sodium Thiosulfate Pre-Treatment on Renal Ischemia-Reperfusion Injury in Kidney Transplantation.

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 µM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 µM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation.

Analytical derivation of optimal irrigation water depth for efficient irrigation scheduling.

Optimal irrigation water depth is a crucial parameter in irrigation engineering, often referred to as root zone depth. It is typically assumed to lie between 1 and 1.5 m below the ground surface, depending on the crop and soil types as well as the practitioner's skill and experience. This approach can lead to inefficient irrigation scheduling. Coupling Richards' equation with the Soil Conservation Service Curve Number (SCS-CN) concept and using the three-phase diagram of soil column widely used in geotechnical engineering, this paper suggests an analytical expression for optimal irrigation water depth providing the maximum storage capacity of a soil depending on its hydraulic/storage properties. The results for winter wheat crop in different hydrologic soil groups show that the use of the proposed concept can lead to savings of 71.79% and 57.69% of irrigation water in sandy soils (HSG-A) compared to that used in traditional irrigation considering lump-sum 1.5 m and 1 m optimal irrigation water depths, respectively. In the case of silty loam soils (HSG-C), these savings can assume 52.42% and 28.62%, respectively. The proposed relation can also be of great help in volumetric assessment of field capacity, moisture content, maximum water storage capacity (of different agricultural soils), and avoiding the issue of waterlogging that may arise from over-irrigation and thus is useful in efficient irrigation scheduling as well as in sustainable agricultural water management.

Challenges in removing an aged spinal cord stimulator: A case study of complete fracture in a 9-year-old S-series paddle lead.

INTRODUCTION: This case report presents an instance of an S-Series™ slim paddle lead fracturing during extraction, highlighting potential risks associated with the removal of this lead. CASE REPORT: A 47-year-old male with complex regional pain syndrome type 2, unresponsive to pharmacotherapy, had undergone the implantation of two spinal cord stimulator (SCS) leads, an Octrode™ cylindrical and an S-series™ slim paddle, using the Epiducer™ system (St Jude Medical) 9 years earlier, with a subsequent intrathecal baclofen pump installed 1 year after SCS. Initially, these interventions stabilized the patient's pain symptoms. However, the diminishing effectiveness of SCS, coupled with a decrease in battery life and increased opioid consumption, necessitated recent surgical procedures. These included the removal and replacement of the implantable pulse generator (IPG) and leads to improve pain management and ensure MRI compatibility. During the removal of the S-series™ slim paddle type lead, complications arose, leading to the retention of an electrode fragment, which necessitated abandoning the replacement of both the IPG and lead. Post-surgical assessments revealed no new neurological impairments, and imaging studies confirmed the stable position of the retained fragment. The patient was discharged with a continued comprehensive pain management plan. CONCLUSION: This case highlights the challenges and risks of percutaneous removal of slim paddle type leads, emphasizing the need for careful procedural planning and consideration of surgical options to avoid complications. Further research is needed to evaluate the long-term durability and removal risks of various SCS lead types.

Schwann cells as a target cell for the treatment of cancer pain.

Tumor erosion and metastasis can invade surrounding tissues, damage nerves, and sensitize the peripheral primary receptors, inducing pain, which can potentially worsen the suffering of patients with cancer. Reception and transmission of sensory signal receptors, abnormal activation of primary sensory neurons, and activation of glial cells are involved in cancer pain. Therefore, exploring promising therapeutic methods to suppress cancer pain is of great significance. Various studies have found that the use of functionally active cells is a potentially effective way to relieve pain. Schwann cells (SCs) act as small, biologically active pumps that secrete pain-relieving neuroactive substances. Moreover, SCs can regulate the progression of tumor cells, including proliferation and metastasis, through neuro-tumor crosstalk, which emphasizes the critical role of SCs in cancer and cancer pain. The mechanisms by which SCs repair injured nerves and exert analgesia include neuroprotection, neurotrophy, nerve regeneration, neuromodulation, immunomodulation, and enhancement of the nerve-injury microenvironment. These factors may ultimately restore the damaged or stimulated nerves and contribute to pain relief. Strategies for pain treatment using cell transplantation mainly focus on analgesia and nerve repair. Although these cells are in the initial stages of nerve repair and pain, they open new avenues for the treatment of cancer pain. Therefore, this paper discusses, for the first time, the possible mechanism of SCs and cancer pain, and new strategies and potential problems in cancer pain treatment.

Skin precursor-derived Schwann cells accelerate in vivo prevascularization of tissue-engineered nerves to promote peripheral nerve regeneration.

Prevascularization strategies have become a hot spot in tissue engineering. As one of the potential candidates for seed cells, skin precursor-derived Schwann cells (SKP-SCs) were endowed with a new role to more efficiently construct prevascularized tissue-engineered peripheral nerves. The silk fibroin scaffolds seeded with SKP-SCs were prevascularized through subcutaneously implantation, which was further assembled with the SKP-SC-containing chitosan conduit. SKP-SCs expressed pro-angiogenic factors in vitro and in vivo. SKP-SCs significantly accelerated the satisfied prevascularization in vivo of silk fibroin scaffolds compared with VEGF. Moreover, the NGF expression revealed that pregenerated blood vessels adapted to the nerve regeneration microenvironment through reeducation. The short-term nerve regeneration of SKP-SCs-prevascularization was obviously superior to that of non-prevascularization. At 12 weeks postinjury, both SKP-SCs-prevascularization and VEGF-prevascularization significantly improved nerve regeneration with a comparable degree. Our figures provide a new enlightenment for the optimization of prevascularization strategies and how to further utilize tissue engineering for better repair.

STUB1 directs FOXQ1-mediated transactivation of Ldha gene and facilitates lactate production in mouse Sertoli cells.

Sertoli cells (SCs) preferentially use glucose to convert to lactate. As an energy source, lactate is essential for survival of developed germ cells (GCs) due to its anti-apoptotic effect. Failure to maintain lactate metabolism homeostasis leads to infertility or germ cell apoptosis. Several Sertoli cell-expressed genes, such as Foxq1 and Gata4, have been identified as critical regulators for lactate synthesis, but the pathways that potentially modulate their expression remain ill defined. Although recent work from our collaborators pointed to an involvement of STIP1 homology and U-box-containing protein 1 (STUB1) in the modulation of Sertoli cell response to GCs-derived IL-1α, a true physiological function of STUB1 signaling in SCs has not been demonstrated. We therefore conditionally ablated Stub1 in SCs using Amh-Cre. Stub1 knockout males exhibited impaired fertility due to oligozoospermia and asthenospermia, possibly caused by lactate deficiency. Furthermore, by means of chromatin immunoprecipitation, in vivo ubiquitination, and luciferase reporter assays, we showed that STUB1 directed forkhead box Q1 (FOXQ1)-mediated transactivation of the lactate dehydrogenase A (Ldha) gene via K63-linked non-proteolytic polyubiquitination, thus facilitating lactate production in follicle-stimulating hormone (FSH)-stimulated SCs. In agreement, overexpression of LDHA by lentivirus infection effectively rescued the lactate production in TM4Stub1-/- cells. Our results collectively identify STUB1-mediated transactivation of FOXQ1 signaling as a post-translationally modified transcriptional regulatory network underlying nursery function in SCs, which may nutritionally contribute to Sertoli cell dysfunction of male infertility.