Optimized performance of 905†nm semiconductor lasers by using the high strain quantum well.

We propose and experimentally demonstrate that the lasing power and characteristic temperature (T0) of 905 nm semiconductor lasers can be optimized by use of the high strain quantum well (HSQW). To fix the lasing wavelength around 905 nm, HSQW with a higher ndium (In) content of the InGaAs gain material than that of the commonly used low strain quantum well (LSQW) requires a thickness-reduced quantum well. Thus, the HSQW has the following two advantages: stronger quantum size effects caused by the deep and thin quantum well, and higher compressive strain caused by a high In content of the InGaAs gain material. With the similar epitaxial structure, laser diodes with HSQW have a characteristic temperature T0 of 207 K and can deliver a higher lasing power with less power saturations. The high strain quantum well optimization method can be extended to other laser diodes with a wavelength near 900 nm with low In content InGaAs quantum wells and other similar low-strain gain material systems.

CK5/6-positive, P63-positive lymphoepithelioma-like hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC), a rare and unique variant of liver cancer, can be divided into lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like intrahepatic cholangiocarcinoma. Dense lymphocytic infiltration is its characteristic pathological feature. In recent years, the number of reported cases of this type has increased each year. Studies have shown that lymphoepithelioma-like cholangiocarcinoma occurs more frequently in Asian women; LELC is associated with Epstein-Barr virus infection of liver cells of epithelial origin. Existing research shows that the prognosis of this tumour is good. CASE SUMMARY: A 38-year-old female patient was hospitalized after 3 mo of abdominal pain and nausea. She had been infected with hepatitis B virus more than 10 years prior. The patient was hospitalized on January 21, 2022. Magnetic resonance imaging showed a 36 mm × 28 mm mass under the envelope of the left inner lobe of the liver. No metastasis of lymph nodes or other organs was observed. After left hemihepatectomy, biopsy and immunohistochemistry yielded a final diagnosis of lymphoepithelial hepatocellular carcinoma. After 12 mo of outpatient follow-up and chemotherapy, no tumour metastases were found on the latest computed tomography examination. CONCLUSION: Herein, the patient was treated surgically and then followed up as an outpatient for 12 mo. This case will further expand our overall knowledge of the diagnosis and treatment of this rare tumor.

m6A mRNA modification potentiates Th17 functions to inflame autoimmunity.

N6-methyladenosine (m6A), the most common and abundant epigenetic RNA modification, governs mRNA metabolism to determine cell differentiation, proliferation and response to stimulation. m6A methyltransferase METTL3 has been reported to control T cell homeostasis and sustain the suppressive function of regulatory T cells (Tregs). However, the role of m6A methyltransferase in other subtypes of T cells remains unknown. T helper cells 17 (Th17) play a pivotal role in host defense and autoimmunity. Here, we found that the loss of METTL3 in T cells caused serious defect of Th17 cell differentiation, and impeded the development of experimental autoimmune encephalomyelitis (EAE). We generated Mettl3f/fIl17aCre mice and observed that METTL3 deficiency in Th17 cells significantly suppressed the development of EAE and displayed less Th17 cell infiltration into central nervous system (CNS). Importantly, we demonstrated that depletion of METTL3 attenuated IL-17A and CCR5 expression by facilitating SOCS3 mRNA stability in Th17 cells, leading to disrupted Th17 cell differentiation and infiltration, and eventually attenuating the process of EAE. Collectively, our results highlight that m6A modification sustains Th17 cell function, which provides new insights into the regulatory network of Th17 cells, and also implies a potential therapeutic target for Th17 cell mediated autoimmune disease.

High-efficiency spectral beam combining of an individual laser diode bar with polarization multiplexing.

In this Letter, a new strategy for the spectral beam combining (SBC) of an individual laser diode (LD) bar based on a polarization multiplexing external cavity is proposed and demonstrated. The maximum combining efficiency is up to 95.51%, which leads to an output power of 76.6 W and an electro-optic conversion efficiency of 48.33% under continuous wave operation at a current of 100 A. Compared to the conventional SBC, the combining efficiency, the output power, and the electro-optical conversion efficiency present improvements of 12%, 10W, and 6%, respectively. The results show that this novel SBC method is a prospective technique for increasing the combining efficiency of LD bars.

Postoperative adjuvant immunotherapy for high-risk hepatocellular carcinoma patients.

Background and aim: Standardized approach to postoperative adjuvant therapy for hepatocellular carcinoma (HCC) remains elusive. This study endeavors to examine the effects of postoperative PD-1 adjuvant therapy on the short-term and long-term prognosis of patients at a heightened risk of post-surgical recurrence. Methods: The data of HCC patients who underwent hepatectomy at our center from June 2018 to March 2023 were collected from the hospital database. Propensity score matching (PSM) was employed to perform a 1:1 match between the postoperative anti-PD-1 antibody group and the postoperative non-anti-PD-1 antibody group. Kaplan-Meier method was utilized to compare the overall survival (OS) and recurrence-free survival (RFS) between the two groups. Cox regression analysis was conducted to identify the prognostic factors affecting patient outcomes. Subgroup analyses were performed for different high-risk factors. Results: Among the 446 patients included in the study, 122 patients received adjuvant therapy with postoperative anti-PD-1 antibodies. After PSM, the PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year OS rates of 93.1%, 86.8%, 78.2%, and 51.1%, respectively, while the non-PD-1 group had rates of 85.3%, 70.2%, 47.7%, and 30.0%. The PD-1 group had postoperative 1-year, 2-year, 3-year, and 4-year RFS rates of 81.7%, 77.0%, 52.3%, and 23.1%, respectively, whereas the non-PD-1 group had rates of 68.4%, 47.7%, and 25.8% in 1-year, 2-year, 3-year. A multifactorial Cox regression analysis revealed that postoperative PD-1 use was a prognostic protective factor associated with OS and RFS. Subgroup analysis results indicated that HCC patients with high recurrence risks significantly benefited from postoperative anti-PD-1 antibody treatment in terms of OS and RFS. Conclusion: For HCC patients with high-risk recurrence factors and undergoing hepatectomy, postoperative adjuvant therapy with anti-PD-1 antibodies can effectively improve their survival prognosis.

Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation.

Metabolic rewiring is essential for Th17 cells' functional identity to sense and interpret environmental cues. However, the environmental metabolic checkpoints with specific regulation of Th17 cells, manifesting potential therapeutic opportunities to autoimmune diseases, remain largely unknown. Here, by screening more than one hundred compounds derived from intestinal microbes or diet, we found that vitamin B5 (VB5) restrains Th17 cell differentiation as well as related autoimmune diseases such as experimental autoimmune encephalomyelitis and colitis. Mechanistically, VB5 is catabolized into coenzyme A (CoA) in a pantothenate kinase (PANK)-dependent manner, and in turn, CoA binds to pyruvate kinase isoform 2 (PKM2) to impede its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation. In humans, reduced serum VB5 levels are found in both IBD and MS patients. Collectively, our study demonstrates a role of VB5 in Th17 cell metabolic reprograming, thus providing a potential therapeutic intervention for Th17 cell-associated autoimmune diseases.

High-brightness and high-efficiency diode laser module based on double wavelength division multiplexing external cavities.

In this Letter, a new, to the best of our knowledge, external cavity structure based on double wavelength division multiplexing external cavities is proposed and demonstrated. The electro-optical conversion efficiency is improved and the brightness of the spectral beam combining diode lasers is enhanced. One wavelength division multiplexing external cavity is placed on the rear-side of the laser emitters to provide the strong optical feedback for wavelength locking and the other wavelength division multiplexing external cavity is placed on the front-side of laser emitters to combine three emitter beams to one beam. A maximum output power of up to 7.5 W is obtained and the brightness of the laser diode is 100 MW cm-2 sr-1 with an electro-optical conversion efficiency of 46.5%. Compared with a standard cavity for spectral beam combining, the use of double wavelength division multiplexing external cavities results in an electro-optical conversion efficiency improvement of 6.5%. The whole structure provides a new technology to achieve high-brightness and high electro-optical conversion efficiency for a laser diode source.

Circulating Tumor Cells as an Indicator of Treatment Options for Hepatocellular Carcinoma Less Than or Equal to 3†cm in Size: A Multi-Center, Retrospective Study.

Background: The status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC. Methods: This study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR). Results: There was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patients. Conclusions: The CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

Guiding Value of Circulating Tumor Cells for Preoperative Transcatheter Arterial Embolization in Solitary Large Hepatocellular Carcinoma: A Single-Center Retrospective Clinical Study.

Background: Large hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment. Methods: This study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup. Results: In CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients. Conclusions: Preoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.

High-power tunable dual-wavelength diode laser with a composite external cavity.

A high-power tunable dual-wavelength composite external cavity architecture obtained by means of a holographic grating and a volume Bragg grating is proposed and demonstrated. The tunable frequency difference of the dual-wavelength output is from 0.41 THz to 3.89 THz. We obtain an output power of 2.1 W when the frequency difference is 1.86 THz. The side-mode suppression ratio of more than 29 dB is suppressed over the entire tunable dual-wavelength output range. The two corresponding wavelengths of the dual-wavelength output basically maintain the same intensity with the smallest power difference of only 0.10%.

Recurrence and Prognostic Value of Circulating Tumor Cells in Resectable Pancreatic Head Cancer: A Single Center Retrospective Study.

Background and Aim: To investigate the effect of preoperative circulation tumor cells (CTCs) on postoperative recurrence and overall survival prognosis of pancreatic head cancer after pancreaticoduodenectomy (PD). Methods: From March 2014 to January 2018, 73 patients with pancreatic head cancer underwent radical resection (R0) in Zhongshan People's Hospital. CTCs in peripheral blood of patients with pancreatic head cancer were detected by "Cyttel" method before PD. Seventy-three patients were divided into positive and negative groups according to the positive criteria. To explore the relationship between the clinical data of CTCs and disease-free survival (DFS) and overall survival (OS). Cox proportional hazards model was used to analyzing the risk factors affecting the postoperative recurrence and the survival prognosis of patients. Results: 41 patients (56.2%) were in the CTC-positive group. Preoperative CTCs were correlated with tumor vascular invasion, CA199 level and postoperative liver metastasis (P < 0.05). Preoperative CTC-positive, lymph node metastasis, vascular invasion, and nerve invasion were independent risk factors for DFS (P < 0.05). Preoperative CTC-positive, tumor diameter > 2 cm and vascular invasion were independent risk factors for OS of patients (P < 0.05). Conclusion: The detection of CTCs before PD is an important factor affecting the DFS and OS of pancreatic head cancer, which is significant in guiding clinical work.

Interleukin-1 and Interleukin-6 Polymorphisms Might Influence Predisposition to Hemorrhagic Cerebral Vascular Diseases: A Meta-Analysis.

BACKGROUND: Interleukin-1 (IL-1) and IL-6 polymorphisms might influence predisposition to hemorrhagic cerebral vascular diseases, but the results of already published studies regarding relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases were still controversial and ambiguous. OBJECTIVES: The authors designed this meta-analysis to more precisely estimate the relationship between IL-1/IL-6 polymorphisms and hemorrhagic cerebral vascular diseases by pooling the results of already published related studies. METHODS: The authors searched PubMed, EMBASE, Web of Science, and CNKI for already published studies. Eighteen already published studies were pooled analyzed in this meta-analysis. RESULTS: The pooled meta-analyses' results showed that distributions of IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms among patients and controls differed significantly. Moreover, distribution of the IL-6 rs1800795 polymorphism among patients and controls from Asians also differed significantly. Further analyses showed similar findings for IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms in aneurysmal subarachnoid hemorrhage (aSAH) subgroup. CONCLUSIONS: This meta-analysis suggested that IL-1A rs1800587, IL-1B rs16944, and IL-6 rs1800796 polymorphisms might influence susceptibility to hemorrhagic cerebral vascular diseases, especially for aSAH. Moreover, IL-6 rs1800795 might influence susceptibility to hemorrhagic cerebral vascular diseases in Asians.

A Single-Center Observational Clinical Study on Factors Associated with Regional Cerebral Oxygen Saturation in Full-Term Newborn Infants During Birth Transition.

BACKGROUND Hypoxic hypoperfusion injury in the brain is a cause of potential injury and even death in the growth period of newborns. Therefore, monitoring regional cerebral oxygen saturation (CrSO2) during this period is particularly important. This observational clinical study from a single center aimed to investigate the factors associated with CrSO2 in full-term newborn infants during birth transition. MATERIAL AND METHODS We enrolled 84 full-term newborn infants delivered by cesarean section. We started the stopwatch with the obstetrician clamping the newborns' umbilical cords and recorded the values of newborns' CrSO2, pulse oxygen saturation (SpO2), pulse rate (PR), end-tidal carbon dioxide (EtCO2), and respiratory rate (RR) at 2 min, 5 min, and 10 min. We weighed the newborns before they left the operating room and used statistical methods to compare the correlation between each observation factor. RESULTS Pearson correlation coefficients between CrSO2 and SpO2 measured at 2 min, 5 min, and 10 min were 0.491, 0.599, and 0.587, respectively (P<0.01). Pearson correlation coefficients between CrSO2 and EtCO2 measured at 2 min, 5 min, and 10 min were -0.304, -0.443, and -0.243, respectively (P<0.05). Regardless of a newborn's weight, PR, or RR, the correlation between any of those factors and the value of CrSO2 measured at the corresponding time point had no significance (P>0.05). CONCLUSIONS This study showed a correlation between CrSO2 and SpO2 and CrSO2 and EtCO2 during birth transition of full-term infants delivered by elective cesarean section, but CrSO2 had no significant correlation with neonatal weight, PR, or RR.

Gut metabolites: make orphans adopted.

A commentary on "A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology".

Suppression of Glutamate Carboxypeptidase II Ameliorates Neuronal Apoptosis from Ischemic Brain Injury.

BACKGROUND: Ischemia stroke is a destructive cerebrovascular disease and a major cause of death and lifelong neurological disability. N-Acetyl-l-aspartyl-l-glutamate (NAAG) is a neurotransmitter in the mammalian brain and involves a variety of physiological and pathological functions including ischemia brain injury. Full understanding of the functions of NAAG peptidase (GCPII) in the pathogenesis of ischemia brain injury is extremely valuable for effective therapies to ischemia stroke. METHODS: The expressions of GCPII and NAAG agonist metabotropic glutamate receptor (mGluR3) and TGFb1 were examined by real-time polymerase chain reaction and western blot. Moreover, GCPII knockdown cells were constructed using lentivirus-mediated transfection. Function and molecular mechanisms of GCPII knockdown on apoptosis induced from hypoxic-ischemic-induced injury in neuronal cells were analyzed. RESULTS: In this study, we found that the expressions of GCPII and mGluR3 were upregulated in CoCl2-induced hypoxia environment in neuronal cells. Moreover, knockdown of GCPII in neuronal cells ameliorated apoptosis from hypoxic-ischemic-induced injury through suppressing expressions of caspase 3 and caspase 9. CONCLUSIONS: Our results highlighted the roles of GCPII in the ischemia brain injury, and might provide an important target in therapeutic implications.

Neuroprotective effects of ischemic preconditioning and postconditioning on global brain ischemia in rats through the same effect on inhibition of apoptosis.

Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic challenge. Therefore, we investigated the effect of ischemic preconditioning and postconditioning on neural cell apoptosis in rats. The result showed that both ischemic preconditioning and postconditioning may attenuate the neural cell death and DNA fragment in the hippocampal CA1 region. Further western blot study suggested that ischemic preconditioning and postconditioning down-regulates the protein of cleaved caspase-3, caspase-6, caspase-9 and Bax, but up-regulates the protein Bcl-2. These findings suggest that ischemic preconditioning and postconditioning have a neuroprotective role on global brain ischemia in rats through the same effect on inhibition of apoptosis.

The effect of ischemic post-conditioning on hippocampal cell apoptosis following global brain ischemia in rats.

We evaluated the effect of brain ischemic post-conditioning on cell apoptosis in the hippocampus following global brain ischemia in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): sham operation, ischemia/reperfusion (I/R) and ischemic post-conditioning (I PostC). Global brain ischemia was induced by four-vessel occlusion. Ischemic post-conditioning consisted of six cycles of 10s/10s reperfusion/reocclusion at the onset of reperfusion. All rats were sacrificed 24 hours or 72 hours after reperfusion. The hippocampal CA1 regions were analysed using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labelling (Tunel) staining technique for determining cell apoptosis. Levels of caspase-3 and Bcl-2 were measured by Western blotting. After 72 hours, fewer Tunel-positive brain cells were observed in rats from the I PostC group than in rats from the I/R group (10.3 ± 2.7% versus 40.8 ± 6.2%, p<0.01). After reperfusion at 24 hours and 72 hours, expression of caspase-3 in the I PostC group was significantly decreased (p<0.01) and expression of Bcl-2 in the I PostC group was significantly increased (p<0.01) compared with the I/R group. We conclude that down-regulation of caspase-3 and up-regulation of Bcl-2 by ischemic post-conditioning may underlie the protective effects of post-conditioning.

Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia.

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis. Expression of glutamate-aspartate transporter remained unchanged at 6 hours-7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.

Neuroprotective effects of ischemic postconditioning on global brain ischemia in rats through upregulation of hippocampal glutamine synthetase.

Brain ischemic postconditioning is the induction of brief periods of ischemia-reperfusion during the early stages following ischemia, and it has been shown to produce neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. Glutamate excitotoxicity is one cause of postischemic neuronal death. Glutamine synthetase (GS) is an enzyme that is expressed in glial cells and may affect glutamate excitotoxicity. We induced global ischemia in rats and performed postconditioning with 6 cycles of 10 seconds reperfusion and 10 seconds reocclusion before final reperfusion. Hematoxylin and eosin staining revealed extensive neuronal loss (44.0 ± 2.8% cell survival) in the hippocampal CA1 region. Ischemic postconditioning decreased neuronal death (82.0 ± 5.6% cell survival; p<0.05). Western blotting revealed significantly increased GS expression in the hippocampus for the ischemia-reperfusion group over time compared with the sham group (p<0.05). Ischemic postconditioning resulted in significantly increased (p<0.05) GS expression compared with both the sham and ischemia-reperfusion groups, suggesting that upregulation of GS expression after ischemia constitutes a neuroprotective mechanism.

Involvement of Glutamate transporter-1 in neuroprotection against global brain ischemia-reperfusion injury induced by postconditioning in rats.

Ischemic postconditioning refers to several transient reperfusion and ischemia cycles after an ischemic event and before a long duration of reperfusion. The procedure produces neuroprotective effects. The mechanisms underlying these neuroprotective effects are poorly understood. In this study, we found that most neurons in the CA1 region died after 10 minutes of ischemia and is followed by 72 hours of reperfusion. However, brain ischemic postconditioning (six cycles of 10 s/10 s reperfusion/re-occlusion) significantly reduced neuronal death. Significant up-regulation of Glutamate transporter-1 was found after 3, 6, 24, 72 hours of reperfusion. The present study showed that ischemic postconditioning decreases cell death and that upregulation of GLT-1 expression may play an important role on this effect.