Bronchial Cryo-Denervation for Severe Asthma: A Pilot Study.

INTRODUCTION: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at a 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse events, technical feasibility, and changes in pulmonary function; asthma control questionnaire-7 (ACQ-7); and asthma control test (ACT). RESULTS: BCD was performed on all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged, and significant improvements from baseline ACQ-7 (mean, -1.19, p = 0.0032) and ACT (mean, 3.18, p = 0.0011) scores were observed since the first month's follow-up after a single lung airway treatment, with similar trends till the end of the 12-month follow-up. CONCLUSION: This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.

Single-cell RNA sequencing indicates cordycepin remodels the tumor immune microenvironment to enhance TIGIT blockade's anti-tumor effect in colon cancer.

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene. As a result, it was hypothesized that cordycepin therapy could enhance the effectiveness of anti-TIGIT therapy. By employing single-cell RNA sequencing analysis of immune cells in the MC38 tumor model, we discovered that cordycepin combined with anti-TIGIT therapy led to a significant increase in the proportion of NK cells within the tumor immune microenvironment. This increased NK cell activity and decreased the expression of inhibitory receptors and exhaustion marker genes. In the combination therapy group, CD8+ T cells had lower exhaustion state scores and increased cytotoxicity, indicating a better immune response. The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4+ T cell and CD8+ T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.

Cordycepin remodels the tumor microenvironment of colorectal cancer by down-regulating the expression of PD-L1.

PURPOSE: Colorectal cancer, as a common malignant tumor, poses a serious threat to human life. Cordycepin, derived from Cordyceps militaris extract, which was established as a capable inhibitor of tumor growth. Nevertheless, the precise antitumor mechanism of cordycepin in colorectal cancer cells remains elusive. METHODS: Herein, our initial focus was to explore the tumor-suppressive impact of cordycepin through its influence on various biological functions in murine colorectal cancer cells, conducted by an in vitro setting. First, we investigated the tumor-suppressive effect of cordycepin on the regulation of biological functions in murine colorectal cancer cells in vitro. Furthermore, we evaluated the in vivo antitumor potential of cordycepin using a mouse preclinical tumor model, and further explored the antitumor mechanism. RESULTS: Our findings revealed that cordycepin effectively inhibit the proliferation, invasion, and migration of murine colon cancer cells. Moreover, there is a substantial reduction in the expression of PD-L1 observed in tumor cells, in response to cordycepin treatment. Collectively, these results demonstrate the significant tumor-suppressive attributes of cordycepin against colorectal cancer. Consequently, our study lays a solid foundation for the potential clinical utilization of cordycepin in cancer therapy. CONCLUSION: Cordycepin inhibits the biological functions of colorectal cancer cells and suppresses tumor growth by reducing the expression of PD-L1.

CircRNAs in BALF exosomes and plasma as diagnostic biomarkers in patients with acute respiratory distress syndrome caused by severe pneumonia.

Background: The transcriptomic studies targeting circular RNAs (circRNAs) in bronchoalveolar lavage fluid (BALF) exosomes of acute respiratory distress syndrome (ARDS) patients caused by severe pneumonia have rarely been reported. This study aimed to screen and validate abnormally expressed circRNAs in exosomes from BALF of patients with ARDS caused by severe pneumonia and then evaluate the diagnostic values of these circRNAs for ARDS. Method: BALF was collected from four patients with ARDS caused by severe pneumonia and four healthy subjects. CircRNA expression profile was obtained by microarray analysis in BALF exosomes of the discovery cohort. The differentially expressed circRNAs in BALF exosomes were verified by real-time quantitative PCR (RT-qPCR) and underwent competitive endogenous RNA (ceRNA) network construction and functional enrichment analysis. Results: A total of 629 circRNAs were differentially expressed in BALF exosomes between ARDS patients and healthy subjects. Nine differentially expressed circRNAs were validated by RT-qPCR, and seven were consistent with the results of microarray analysis. CeRNA network analysis was performed for hsa_circRNA_002809, hsa_circRNA_042882, and hsa_circRNA_104034. Functional enrichment analysis showed that the target genes were mainly associated with hypoxia-induced damage, inflammatory response, and the HIF-1 signaling pathway. Hsa_circRNA_042882 and hsa_circRNA_104034 can be regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia, with remarkable sensitivity and specificity of the area under the curve of 0.8050 and 1 or 0.835 and 0.799, respectively. Conclusion: This study obtained circRNA expression profiles of ARDS patients, and hsa_circRNA_042882 and hsa_circRNA_104034 were regarded as promising diagnostic biomarkers for patients with ARDS caused by severe pneumonia.

Cordycepin synergizes with CTLA-4 blockade to remodel the tumor microenvironment for enhanced cancer immunotherapy.

The strategy of using immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, leading to remarkable clinical outcomes. However, certain cancer types and patient demographics continue to face unique challenges. As a result, it is vital to investigate combination therapies that involve ICIs to boost therapeutic efficacy. Cordycepin, an adenosine derivative composed of adenine and pentose, holds immense promise for treating inflammation and cancer. Our recent research has demonstrated that the combined treatment of cordycepin and the anti-CD47 antibody significantly curtails tumor growth and extends the lifespan of tumor-bearing mice. In the current study, we showed that the combination of cordycepin and CTLA-4 blockade had a profound impact on suppressing tumor growth. We utilized the MC38 and CT26 tumor models to evaluate the therapeutic effect of cordycepin, CTLA-4 blockade, and their combined approach. Flow cytometry results unveiled that cordycepin, when combined with CTLA-4 blockade, considerably augmented the presence of tumor-infiltrating CD8+T cells and diminished the population of Foxp3+Tregs within the tumor microenvironment (TME). Additionally, we employed single-cell analysis to examine the TME's reconfiguration upon the combined treatment of anti-CTLA-4 and cordycepin. We observed a significant impact on inhibiting tumor growth and substantially extended survival in tumor-bearing mice. Our data also demonstrated an increased proportion of effector CD8+T cells in the combined treatment group compared to all other groups, while exhausted CD8+T cells diminished in the combined group compared to the anti-CTLA-4 treatment alone. In conclusion, our findings supported the idea that combining cordycepin and CTLA-4 blockade could modify the effector and exhaustion status of CD8+T cells, thereby bolstering CD8+T-cell-mediated anti-tumor immunity in the TME. Collectively, our current study successfully established a combination therapeutic strategy utilizing cordycepin and CTLA-4 blockade. This strategy demonstrated a significant synergistic effect against cancer, highlighting its importance in cancer treatment.

Combination of transbronchial cryobiopsy based clinic-radiologic-pathologic strategy and metagenomic next-generation sequencing for differential diagnosis of rapidly progressive diffuse parenchymal lung diseases.

Background: The complicated spectrum of rapidly progressive diffused parenchymal lung diseases (RP-DPLD) creates obstacles to the precise diagnosis and treatment. We evaluated the differential diagnostic value of transbronchial cryobiopsy (TBCB) based clinic-radiologic-pathologic (CRP) strategy combined with bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in RP-DPLD patients. Methods: RP-DPLD patients who underwent the diagnostic strategy of TBCB-based CRP combined with BALF mNGS at Shanghai East Hospital from May 2020 to Oct 2022 were retrospectively analyzed. Clinical characteristics were summarized, including demographic data, high-resolution computed tomography (HRCT) findings, histopathology of TBCB and microbiological results. Diagnostic value of the combined strategy, as well as the sensitivity, specificity, and positive detection rates of mNGS were evaluated. Results: A total of 115 RP-DPLD patients were enrolled, with a mean age of 64.4 years old and a male proportion of 54.8%. The pulmonary imaging findings in most patients were complex and diverse, with all patients showing bilateral lung diffuse lesions in HRCT, and progressively aggravated imaging changes within one month. After combining TBCB-based CRP strategy with mNGS, all participants received a corresponding diagnosis with 100% diagnostic yield. In these patients, 58.3% (67/115) were diagnosed with noninfectious RP-DPLD and 41.7% (48/115) with infection-related RP-DPLD. There were 86.1% of cases with known etiology according to the DPLD classification. BALF mNGS and traditional pathogen detection methods were performed in all patients, the positive detection rates were 50.4% (58/115) and 32.2% (37/115), respectively. Meanwhile, the mNGS showed significantly higher sensitivity and negative predictive value than the traditional pathogen detection methods for the diagnosis of infection-related RP-DPLD (100% vs 60.4% (p<0.001), 100% vs 75.6% (p<0.001), respectively). Among noninfectious RP-DPLD patients, the true negative rate of mNGS was 85.1% (57/67). All patients had their treatment regimen modified and the 30-day mortality was 7.0%. Conclusion: The novel strategy of TBCB-based CRP combined with mNGS provided dependable and sufficient evidence for the diagnosis, meanwhile further improved the accuracy of RP-DPLD treatment, as well as the prognosis of patients. Our results highlight the significant value of combined strategy in determining whether the RP-DPLD patients were infection associated or not.

Synergistic effect of CD47 blockade in combination with cordycepin treatment against cancer.

Cordycepin is widely considered a direct tumor-suppressive agent. However, few studies have investigated as the effect of cordycepin therapy on the tumor microenvironment (TME). In our present study, we demonstrated that cordycepin could weaken the function of M1-like macrophages in the TME and also contribute to macrophage polarization toward the M2 phenotype. Herein, we established a combined therapeutic strategy combining cordycepin and an anti-CD47 antibody. By using single-cell RNA sequencing (scRNA-seq), we showed that the combination treatment could significantly enhance the effect of cordycepin, which would reactivate macrophages and reverse macrophage polarization. In addition, the combination treatment could regulate the proportion of CD8+ T cells to prolong the progression-free survival (PFS) of patients with digestive tract malignancies. Finally, flow cytometry validated the changes in the proportions of tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs). Collectively, our findings suggested that the combination treatment of cordycepin and the anti-CD47 antibody could significantly enhance tumor suppression, increase the proportion of M1 macrophages, and decrease the proportion of M2 macrophages. In addition, the PFS in patients with digestive tract malignancies would be prolonged by regulating CD8 + T cells.

Comparison of high-flow nasal cannula and conventional oxygen therapy for high-risk patients during bronchoscopy examination: protocol for a randomized controlled trial.

INTRODUCTION: High-flow nasal cannula (HFNC) has been proven to improve oxygenation and avoid intubation in hypoxemic patients. It has also been utilized during endoscopy examination to reduce the incidence of hypoxia. However, little is known about the effects of HFNC versus conventional oxygen therapy (COT) on oxygenation during bronchoscopy examination via nasal route; particularly, no study has compared the use of HFNC with that of COT at similar FIO2 for patients who have high-risk factors of desaturation during bronchoscopy examination. METHODS AND ANALYSIS: This randomized controlled trial will be implemented in four academic centers in China. Patients who have high-risk factors including hypoxemia, hypercapnia, morbid obesity, and narrow airway will be enrolled to use HFNC or COT during bronchoscopy examination. In the HFNC group, the initial gas flow will be set at 50 L/min with a fraction of inspired oxygen (FIO2) at 0.45, if the patient tolerates, the flow can be increased to 60L/min at most, while in the COT group, oxygen flow will be set at 6 L/min via a conventional nasal cannula. After 5 min pre-oxygenation, the bronchoscope will be inserted via the nasal route. Vital signs, oxygenation (SpO2), and transcutaneous CO2 (PtCO2) will be continuously monitored. The primary outcome is the incidence of hypoxemia, defined as SpO2 < 90% for 10 s during bronchoscopy examination, and secondary outcomes include the need for treatment escalation and adverse events. DISCUSSION: Hypoxia is a common complication of bronchoscopy, our study attempted to demonstrate that HFNC may reduce the probability of hypoxia during bronchoscopy in high-risk patients. The results will be disseminated through peer-reviewed journals and national and international conferences. TRIAL REGISTRATION: http://www.chictr.org.cn/ : ChiCTR2100055038. Registered on 31 December 2021.

TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation Against Cancer.

Background: Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy. Methods: In the present study, we examined the expression of TIGIT using a preclinical mouse model treated with MWA. Moreover, we evaluated the antitumor functions of MWA alone or in combination with TIGIT blockade by monitoring tumor growth and survival of the mice. Besides, we also detected the numbers of tumor-infiltrating lymphocytes (TILs), and effector molecules of CD8+ T cells using flow cytometry. Finally, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups. Results: The expression of TIGIT in various immune cells was up-regulated after MWA, and the addition of TIGIT blockade to MWA prolonged survival and delayed tumor growth in the MC38 tumor model. Taken together, our findings showed that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME) using flow cytometry and scRNA-seq analysis. Conclusions: TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.

Spatially resolved fibre cavity ring down spectroscopy.

This paper presents a fibre cavity ring down spectroscopy probed by Rayleigh scattering optical frequency domain reflectometry (OFDR), which provides spatial location of stimuli and improved signal to noise ratio for distributed sensing measurements. A section of optical fibre was integrated into an active fibre ring cavity with optical gain and interrogated by the OFDR system for 11 cycles with a single laser scan. Through the cavity ring down configuration, root-mean-squared (RMS) noise of distributed temperature and strain measurements was reduced to 6.9 mK and less than 0.1 µÎµ, respectively for 1-cm spatially resolved measurements. Our work shows that the active fibre cavity configuration can be combined with distributed fibre sensing schemes to achieve both high spatial resolution and high sensitivity measurements.

Clinical features and efficacy of antiviral drug, Arbidol in 220 nonemergency COVID-19 patients from East-West-Lake Shelter Hospital in Wuhan: a retrospective case series.

OBJECTIVE: We aimed to describe the features of 220 nonemergency (mild or common type) COVID-19 patients from a shelter hospital, as well as evaluate the efficiency of antiviral drug, Arbidol in their disease progressions. METHODS: Basic clinical characteristics were described and the efficacy of Arbidol was evaluated based on gender, age, maximum body temperature of the patients. RESULTS: Basically, males had a higher risk of fever and more onset symptoms than females. Arbidol could accelerate fever recovery and viral clearance in respiratory specimens, particularly in males. Arbidol also contributed to shorter hospital stay without obvious adverse reactions. CONCLUSIONS: In the retrospective COVID-19 cohort, gender was one of the important factors affecting patient's conditions. Arbidol showed several beneficial effects in these patients, especially in males. This study brought more researches enlightenment in understanding the emerging infectious disease.

Epidemiological features and medical care-seeking process of patients with COVID-19 in Wuhan, China.

BACKGROUND: We aimed to investigate the epidemiological and clinical features, and medical care-seeking process of patients with the 2019 coronavirus disease (COVID-19) in Wuhan, China, to provide useful information to contain COVID-19 in other places with similar outbreaks of the virus. METHODS: We collected epidemiological and clinical information of patients with COVID-19 admitted to a makeshift Fangcang hospital between 7 and 26 February, 2020. The waiting time of each step during the medical care-seeking process was also analysed. RESULTS: Of the 205 patients with COVID-19 infection, 31% had presumed transmission from a family member. 10% of patients had hospital-related transmission. It took as long as a median of 6 days from the first medical visit to receive the COVID-19 nucleic acid test and 10 days from the first medical visit to hospital admission, indicating early recognition of COVID-19 was not achieved at the early stage of the outbreak, although these delays were shortened later. After clinical recovery from COVID-19, which took a mean of 21 days from illness onset, there was still a substantial proportion of patients who had persistent SARS-CoV-2 infection. CONCLUSIONS: The diagnostic evaluation process of suspected patients needs to be accelerated at the epicentre of the outbreak and early isolation of infected patients in a healthcare setting rather than at home is urgently required to stop the spread of the virus. Clinical recovery is not an appropriate criterion to release isolated patients and as long as 4 weeks' isolation for patients with COVID-19 is not enough to prevent the spread of the virus.

Feasibility, effectiveness, and safety of a novel cryo-balloon targeted lung denervation technique in an animal model.

BACKGROUND AND OBJECTIVE: Targeted lung denervation (TLD) is a pulmonary interventional procedure for COPD that aims to disrupt parasympathetic nerve input to the lung to reduce the clinical consequences of cholinergic hyperactivity. TLD has been proven to be a safe procedure and effectively alleviate symptoms and reduce the onset of exacerbation. In the present study, we developed a novel cryo-balloon TLD system and evaluated its feasibility, safety, and effectiveness. METHODS: A preclinical study was performed on twelve sheep, four were tested for airway resistance alterations before and after TLD, two were tested for the Hering-Breuer reflex (HBR) and the remaining six sheep were evaluated for 28 days to assess the safety and effectiveness of the procedure. RESULTS: After an observation period of 28 days, significant disruption of vagal innervation to the lung could be validated by both histological and physiological assessments. The operation time was shorter than traditional procedure, with minimal adjacent tissue injury and no device-related adverse events. CONCLUSIONS: The novel cryo-balloon TLD procedure was feasible, safe, and effective. In comparison with the traditional procedure, this treatment system required shorter operation time and caused less denervation-induced damage to adjacent tissues.

Distributed Optical Fiber Sensors with Ultrafast Laser Enhanced Rayleigh Backscattering Profiles for Real-Time Monitoring of Solid Oxide Fuel Cell Operations.

This paper reports a technique to enhance the magnitude and high-temperature stability of Rayleigh back-scattering signals in silica fibers for distributed sensing applications. With femtosecond laser radiation, more than 40-dB enhancement of Rayleigh backscattering signal was generated in silica fibers using 300-nJ laser pulses at 250 kHz repetition rate. The laser-induced Rayleigh scattering defects were found to be stable from the room temperature to 800 °C in hydrogen gas. The Rayleigh scatter at high temperatures was correlated to the formation and modification of nanogratings in the fiber core. Using optical fibers with enhanced Rayleigh backscattering profiles as distributed temperature sensors, we demonstrated real-time monitoring of solid oxide fuel cell (SOFC) operations with 5-mm spatial resolution at 800 °C. Information gathered by these fiber sensor tools can be used to verify simulation results or operated in a process-control system to improve the operational efficiency and longevity of SOFC-based energy generation systems.

A compact field-portable double-pulse laser system to enhance laser induced breakdown spectroscopy.

This paper reports the development of a compact double-pulse laser system to enhance laser induced breakdown spectroscopy (LIBS) for field applications. Pumped by high-power vertical-surface emitting lasers, the laser system that produces 16 ns pulse at 12 mJ/pulse with total weight less than 10 kg is developed. The inter-pulse delay can be adjusted from 0µs with 0.5µs increment. Several LIBS experiments were carried out on NIST standard aluminum alloy samples. Comparing with the single-pulse LIBS, up to 9 times enhancement in atomic emission line was achieved with continuum background emission reduced by 70%. This has led to up to 10 times improvement in the limit of detection. Signal stability was also improved by 128% indicating that a more robust and accurate LIBS measurement can be achieved using a compact double-pulse laser system. This paper presents a viable and field deployable laser tool to dramatically improve the sensitivity and applicability of LIBS for a wide array of applications.

A case of chromoblastomycosis by Fonsecaea nubica indicating a possible insect route of transmission.

A first auricular case of chromoblastomycosis due to Fonsecaea nubica is reported in a 42-year-old Chinese male. He presented a slightly verrucous, erythematous plaque on his right auricle which had gradually extended over a 10-year period, and the patient reported a history of dog flea sting before onset of the lesions. Diagnosis was based on histopathological and mycological examination of clinical samples, which revealed muriform cells. Identification of the aetiological agent was assessed by morphological characteristics and confirmed at species level by sequencing of the rDNA internal transcribed spacer (ITS). The patient showed marked clinical improvement after 3 months combination therapy with itraconazole and terbinafine. The possible mode of transmission of auricular chromoblastomycosis is discussed.

Development of a compact vertical-cavity surface-emitting laser end-pumped actively Q-switched laser for laser-induced breakdown spectroscopy.

This paper reports the development of a compact and portable actively Q-switched Nd:YAG laser and its applications in laser-induced breakdown spectroscopy (LIBS). The laser was end-pumped by a vertical-cavity surface-emitting laser (VCSEL). The cavity lases at a wavelength of 1064 nm and produced pulses of 16 ns with a maximum pulse energy of 12.9 mJ. The laser exhibits a reliable performance in terms of pulse-to-pulse stability and timing jitter. The LIBS experiments were carried out using this laser on NIST standard alloy samples. Shot-to-shot LIBS signal stability, crater profile, time evolution of emission spectra, plasma electron density and temperature, and limits of detection were studied and reported in this paper. The test results demonstrate that the VCSEL-pumped solid-state laser is an effective and compact laser tool for laser remote sensing applications.

High resolution monitoring of strain fields in concrete during hydraulic fracturing processes.

We present a distributed fiber optic sensing scheme to image 3D strain fields inside concrete blocks during laboratory-scale hydraulic fracturing. Strain fields were measured by optical fibers embedded during casting of the concrete blocks. The axial strain profile along the optical fiber was interrogated by the in-fiber Rayleigh backscattering with 1-cm spatial resolution using optical frequency domain reflectometry (OFDR). The 3D strain fields inside the cubes under various driving pressures and pumping schedules were measured and used to characterize the location, shape, and growth rate of the hydraulic fractures. The fiber optic sensor detection method presented in this paper provides scientists and engineers an unique laboratory tool to understand the hydraulic fracturing processes via internal, 3D strain measurements with the potential to ascertain mechanisms related to crack growth and its associated damage of the surrounding material as well as poromechanically-coupled mechanisms driven by fluid diffusion from the crack into the permeable matrix of concrete specimens.

Contributions of multiple refugia during the last glacial period to current mainland populations of Korean pine (Pinus koraiensis).

The northern microrefugia that existed during the Last Glacial Maximum (LGM) are a key factor in the demographic history of species. Pinus koraiensis has a unique distribution in northeast Asia. The Changbai Mountains and the Korean peninsula (CM/KP) are usually considered to be the LGM refugia for P. koraiensis. However, the Xiaoxingan Range (XR), at the northern part of this species' distribution, is another possible refugium. We used chloroplast sequencing and ten nuclear single-copy gene loci to calculate the genetic diversity pattern of P. koraiensis. The probabilities of a single LGM refugium and of multiple LGM refugia were calculated based on approximate Bayesian computation. The effect of the latitudinal gradient on genetic diversity was not significant. However, unique alleles occurred at low frequencies in CM/KP and XR. A conservative estimate of the coalescence time between CM/KP and XR is 0.4 million years ago, a time prior to the LGM. Gene flow between CM/KP and XR was estimated to be more than one in per generation, an amount that may be sufficient to limit genetic divergence between the regions. Our study strongly supports the hypothesis that XR was another LGM refugium in addition to CM/KP.

Fiber-optic flow sensors for high-temperature environment operation up to 800°C.

This Letter presents an all-optical high-temperature flow sensor based on hot-wire anemometry. High-attenuation fibers (HAFs) were used as the heating elements. High-temperature-stable regenerated fiber Bragg gratings were inscribed in HAFs and in standard telecom fibers as temperature sensors. Using in-fiber light as both the heating power source and the interrogation light source, regenerative fiber Bragg grating sensors were used to gauge the heat transfer from an optically powered heating element induced by the gas flow. Reliable gas flow measurements were demonstrated between 0.066 m/s and 0.66 m/s from the room temperature to 800°C. This Letter presents a compact, low-cost, and multiflexible approach to measure gas flow for high-temperature harsh environments.