Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.

Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion.

BACKGROUND: This is a qualitative study to identify implementation challenges for deploying triple artemisinin-based combination therapy (TACT) in the Greater Mekong Subregion (GMS) of Southeast Asia and to explore strategies to overcome these challenges. METHODS: In-depth interviews were conducted in three countries that have repeatedly been confronted with ACT failures: Cambodia, Vietnam, and Lao PDR. Thirty-nine key stakeholders in the healthcare systems in these countries were interviewed. One participatory workshop was conducted in Cambodia, where scenarios for potential TACT deployment were discussed. RESULTS: The results section is organized around four strategic themes that emerged from the data: policy support, data and evidence, logistics and operation, and downstream engagement. The study revealed that countries in the GMS currently rely on ACT to eliminate Plasmodium falciparum malaria by 2025. TACT is, however, considered to be a useful backup strategy in case of future treatment failures and to prevent the re-establishment of malaria. The study showed that a major challenge ahead is to engage decision makers and healthcare providers into deploying TACT, given the low case incidence of falciparum malaria in the GMS. Interview respondents were also skeptical whether healthcare providers would be willing to engage in new therapies for a disease they hardly encounter anymore. Hence, elaborate information dissemination strategies were considered appropriate and these strategies should especially target village malaria workers. Respondents proposed several regulatory and programmatic strategies to anticipate the formation of TACT markets in the GMS. These strategies include early dossier submission to streamline regulatory procedures, early stakeholder engagement strategies to shorten implementation timelines, and inclusion of TACT as second-line therapy to accelerate their introduction in case they are urgently needed. CONCLUSIONS: This paper presents a qualitative study to identify implementation challenges for deploying TACT in the GMS and to explore strategies to overcome these challenges. The findings could benefit researchers and decision makers in strategizing towards potential future deployment of TACT in the GMS to combat artemisinin and partner drug resistance.

Single-Dose Rifapentine in Household Contacts of Patients with Leprosy.

BACKGROUND: Previous studies have suggested that a single dose of rifampin has protective effects against leprosy in close contacts of patients with the disease. Rifapentine was shown to have greater bactericidal activity against Mycobacterium leprae than rifampin in murine models of leprosy, but data regarding its effectiveness in preventing leprosy are lacking. METHODS: We conducted a cluster-randomized, controlled trial to investigate whether single-dose rifapentine is effective in preventing leprosy in household contacts of patients with leprosy. The clusters (counties or districts in Southwest China) were assigned to one of three trial groups: single-dose rifapentine, single-dose rifampin, or control (no intervention). The primary outcome was the 4-year cumulative incidence of leprosy among household contacts. RESULTS: A total of 207 clusters comprising 7450 household contacts underwent randomization; 68 clusters (2331 household contacts) were assigned to the rifapentine group, 71 (2760) to the rifampin group, and 68 (2359) to the control group. A total of 24 new cases of leprosy occurred over the 4-year follow-up, for a cumulative incidence of 0.09% (95% confidence interval [CI], 0.02 to 0.34) with rifapentine (2 cases), 0.33% (95% CI, 0.17 to 0.63) with rifampin (9 cases), and 0.55% (95% CI, 0.32 to 0.95) with no intervention (13 cases). In an intention-to-treat analysis, the cumulative incidence in the rifapentine group was 84% lower than that in the control group (cumulative incidence ratio, 0.16; multiplicity-adjusted 95% CI, 0.03 to 0.87; P = 0.02); the cumulative incidence did not differ significantly between the rifampin group and the control group (cumulative incidence ratio, 0.59; multiplicity-adjusted 95% CI, 0.22 to 1.57; P = 0.23). In a per-protocol analysis, the cumulative incidence was 0.05% with rifapentine, 0.19% with rifampin, and 0.63% with no intervention. No severe adverse events were observed. CONCLUSIONS: The incidence of leprosy among household contacts over 4 years was lower with single-dose rifapentine than with no intervention. (Funded by the Ministry of Health of China and the Chinese Academy of Medical Sciences; Chinese Clinical Trial Registry number, ChiCTR-IPR-15007075.).

Long-term presence of autoantibodies in plasma of cured leprosy patients.

Autoantibodies have been detected in leprosy patients, indicating that infection with M. leprae may lead to autoimmune disorders. However, whether autoimmune response last until patients are cured is unknown. Knowing the autoimmune response in cured leprosy patients is essential to identify whether symptoms are caused by leprosy itself or by other immune-related diseases. This knowledge is essential for the ongoing health management in cured leprosy patients where autoimmune disorders still exist. In our study, we selected six autoantibodies, including anticardiolipin antibody of IgG (ACA), anti-nuclear antibody (ANA), extractable nuclear antigen antibody (ENA), anti-streptolysin O (ASO), anti-double stranded DNA antibody (dsDNA), and rheumatoid factor (RF), that had been reported in leprosy patients as typical autoantibodies. We tested the six typical autoantibodies combined with LACC1, which encodes a protein associated with autoimmune disease such as Crohn's disease and is also the susceptible gene conferring leprosy risk, in cured leprosy patients through ELISA to assess the cured patient's immune status. We observed high positive rates of autoantibodies in cured leprosy patients, and the average plasma levels of five (ACA, ANA, ENA, ASO, and RF) out of the six autoantibodies were significantly higher in cured leprosy patients than in controls. The positive detection of autoantibodies is independent of the recovery period. Moreover, the level of these autoantibodies showed a strong positive correlation with the level of LACC1 in both controls and cured patients. This study showed that there is long-term autoimmunological activation in leprosy patients, even after decades of recovery. Autoimmune responses may influence the development and prognosis of leprosy. Special care should be given to posttreatment or cured leprosy patients regarding long-term autoimmunological activation.

Utility of Multi-target Nested PCR and ELISPOT Assays for the Detection of Paucibacillary Leprosy: A Possible Conclusion of Clinical Laboratory Misdiagnosis.

The diagnosis of paucibacillary (PB) leprosy often possesses a diagnostic challenge, especially for pure neuritic and lesser skin lesions with the zero bacillary load, requiring a sensitive and accurate diagnostic tool. We have included 300 clinically diagnosed new leprosy cases (comprising 98 PB cases) and analyzed the sensitivity and specificity of PB leprosy cases by nested PCR with folP, gyrA, rpoB, RLEP, and 16SrRNA and Enzyme-linked Immunospot Assay test (ELISPOT) with MMPII, NDO-BSA, and LID-1 antigens by detecting interferon gamma (IFN-γ) release. The overall positivity rates of genes tested in 300 clinical specimens were identified as 55% of 16SrRNA, 59% of RLEP, 59.3% of folP, 57.3% of rpoB, 61% of gyrA while 90% of nested folP, 92.6% of nested rpoB, and 95% of nested gyrA, and 285 (95%) of at least one gene positive cases. For PB specimens, 95% PCR positivity was achieved by three tested genes in nested PCR. The data obtained from ELISPOT for three antigens were analyzed for IFN-γ expression with 600 subjects. Among 98 PB leprosy cases, the sensitivity of MMP II, LID-1, and NDO-BSA was 90%, 87%, and 83%, respectively, and the specificity was 90%, 91%, and 86%, respectively. The total number of cases positive for at least one antigen was 90 (91.8%) in PB, which is significantly higher than that in multibacillary (MB) leprosy (56.7%). The combination of multi-targets nested PCR and ELISPOT assay provides a specific tool to early clinical laboratory diagnosis of PB leprosy cases. The two assays are complementary to each other and beneficial for screening PB patients.

Factors Influencing Leprosy Incidence: A Comprehensive Analysis of Observations in Wenshan of China, Nepal, and Other Global Epidemic Areas.

Leprosy remains endemic in some regions and is a global health concern. However, the possible causes and risk factors of the disease remain unclear. Data in Wenshan, China were collected from the Wenshan Institute of Dermatology (1986-2015); data in Nepal were obtained from the Leprosy Control Division, Department of Health Services, Nepal (2011 to 2015); and data from Indonesia, India, and Brazil were collected from WHO records. We assessed the epidemiological trends of leprosy in Wenshan and compared the features of possible causes and risk factors with those of other countries. We then performed a descriptive and statistical analysis to make our study more purposeful and definitive. A total of 3,376 cases were detected in Wenshan from 1986 to 2015. The overall prevalence rate (PR) of leprosy presented a decreasing trend with a peak (4.9/10,000 population) in 1986. The detection of new leprosy cases was higher in males than in females. Visible deformity increased every year since 2005 with a disability of 34.8% in 2015 among new cases. In Nepal, 2,461 leprosy patients received multi-drug therapy (MDT) in 2015 which corresponded to the PR of 0.89/10,000 population. Geographic latitude and socio-economic situations appeared to be the main causes of leprosy, and the healthcare condition was an important factor associated with leprosy incidence. The introduction of MDT effectively reduced leprosy prevalence worldwide. Wenshan (China), Nepal, and other countries share similarities in various aspects with respect to socio-cultural features, geographical distribution, environmental factors, and economic situation, which may contribute to leprosy being endemic in these areas.

Predictive nomogram for leprosy using genetic and epidemiological risk factors in Southwestern China: Case-control and prospective analyses.

BACKGROUND: There is a high incidence of leprosy among house-contacts compared with the general population. We aimed to establish a predictive model using these genetic factors along with epidemiological factors to predict leprosy risk of leprosy household contacts (HHCs). METHODS: Weighted genetic risk score (wGRS) encompassing genome wide association studies (GWAS) variants and five non-genetic factors were examined in a case-control design associated with leprosy risk including 589 cases and 647 controls from leprosy HHCs. We constructed a risk prediction nomogram and evaluated its performance by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling with 1000 resamples and a prospective design including 1100 HHCs of leprosy patients. FINDING: The C-index for the risk model was 0·792 (95% confidence interval [CI] 0·768-0·817), and was confirmed to be 0·780 through bootstrapping validation. The calibration curve for the probability of leprosy showed good agreement between the prediction of the nomogram and actual observation. HHCs were then divided into the low-risk group (nomogram score ≤ 81) and the high-risk group (nomogram score > 81). In prospective analysis, 12 of 1100 participants had leprosy during 63 months' follow-up. We generated the nomogram for leprosy in the validation cohort (C-index 0·773 [95%CI 0·658-0·888], sensitivity75·0%, specificity 66·8%). Interpretation The nomogram achieved an effective prediction of leprosy in HHCs. Using the model, the risk of an individual contact developing leprosy can be determined, which can lead to a rational preventive choice for tracing higher-risk leprosy contacts. FUNDING: The ministry of health of China, ministry of science and technology of China, Chinese academy of medical sciences, Jiangsu provincial department of science and technology, Nanjing municipal science and technology bureau.

Towards the elimination of leprosy in Yunnan, China: A time-series analysis of surveillance data.

BACKGROUND: This study reviews the progress of leprosy elimination in Yunnan, China, over the past 30 years and identifies the challenges for the next stage of the program. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from the Leprosy Management Information System in China (LEPMIS). The progress made in the elimination of leprosy between 1990 and 2019 was measured. We defined two time periods, time period 1 (1990-2003) and time period 2 (2004-2019), because multidrug therapy (MDT) was launched for the treatment of leprosy in 1990 and a special fund from the central government was established for leprosy in 2004. During the past 30 years, the number of newly detected leprosy patients in Yunnan has steadily declined. In total, 703 newly detected leprosy patients were reported in 1990, and 353 and 136 cases were reported at the end of 2003 and 2019, respectively. At the end of 1990, 90.7% (117/129) of counties in Yunnan Province were identified as leprosy-endemic counties (>1 case per 100,000 population). By the end of 2003 and 2019, 39.3% (46/117) and 85.5% (100/117) of the leprosy-endemic counties, respectively, had dropped below the elimination threshold. The main challenges are the remaining leprosy-endemic counties, the high rate of cases with a contact history, insufficient early detection, and leprosy cases resulting in physical disability. CONCLUSIONS/SIGNIFICANCE: A multifaceted strategy for leprosy elimination in Yunnan Province has been successfully implemented, and remarkable progress has been made in the elimination of leprosy in this area. The priorities for leprosy elimination in the next stage are securing sustainable support and investment from the government, establishing an effective surveillance system, ensuring prompt early detection, providing treatment with MDT, preventing transmission of M. leprae, preventing disability, providing health education, and preventing recurrence of the epidemic situation of leprosy.

[Clinical application of extracorporeal pneumatic reduction combined with bone-filled mesh bag implantation for the treatment of thoracolumbar osteoporotic burst fracture without spinal cord injury].

OBJECTIVE: To compare the clinical efficacy of pneumatic reduction combined with bone-filled mesh bag implantation and pneumatic reduction combined with kyphoplasty in the treatment of thoracolumbar burst fracture without spinal cord injury. METHODS: The clinical data of 160 patients with thoracolumbar osteoporotic burst fracture without spinal cord injury treated from January 2014 to July 2017 were retrospectively analyzed. There were 66 males and 94 females, aged from 72 to 84 years old with an average of 76.4 years old. The patients were divided into two groups according to different surgical methods, including 80 cases of pneumatic reduction combined with bone-filled mesh bag implantation(treatment group) and 80 cases of pneumatic reduction combined with kyphoplasty(control group). The intraoperative bone cement leakage rate was compared between two groups. The height of the injured vertebrae was measured by X-rays preoperatively and 6-month postoperatively in order to assess height loss of injured vertebrae. VAS score and ODI score were used for follow-up to assess lumbar back pain and autonomic dysfunction before surgery and 2 weeks, 6 months, 1 year after surgery. RESULTS: In treatment group, 3 cases occurred bone cement leakage during operation and leakage rate was 3.75%(3/80); In control group, 14 cases had cement leakage with leakage rate of 17.5%; The difference between two groups was statistically significant(P<0.05). All patients were followed up for 13 to 24 months with an average of 14.6 months. Among them, 2 cases occurred postoperative infections which were superficial infections. After oral antibiotics and outpatient treatment infections were controlled. At 6 months after surgery, the height of the injured vertebra was measured by X-ray. Treatment group recovered (5.12±1.31) % and control group recovered (14.11±1.17) %. The difference between two groups was statistically significant (P<0.05). At 1 year after surgery, ODI score was 4.03±1.62 in treatment group and 10.03±1.54 in control group. The difference between two groups was statistically significant(P<0.05). VAS score was 1.03±0.62 in treatment group and 2.67±0.55 in control group. The difference between groups was statistically significant(P<0.05). CONCLUSIONS: Extracorporeal pneumatic reduction combined with bone-filled mesh bag implantation technique can significantly reduce the occurrence of intraoperative cement leakage in the treatment of thoracolumbar osteoporotic burst fractures, effectively improve reposition of the injured vertebrae, relieve the pain and recover the function of lower back. However, high price of bone-filled mesh bags obstructs its clinical popularization.

Missense Variants in HIF1A and LACC1 Contribute to Leprosy Risk in Han Chinese.

Genome-wide association studies (GWASs) and genome-wide linkage studies (GWLSs) have identified numerous risk genes affecting the susceptibility to leprosy. However, most of the reported GWAS hits are noncoding variants and account for only part of the estimated heritability for this disease. In order to identify additional risk genes and map the potentially functional variants within the GWAS loci, we performed a three-stage study combining whole-exome sequencing (WES; discovery stage), targeted next-generation sequencing (NGS; screening stage), and refined validation of risk missense variants in 1,433 individuals with leprosy and 1,625 healthy control individuals from Yunnan Province, Southwest China. We identified and validated a rare damaging variant, rs142179458 (c.1045G>A [p.Asp349Asn]) in HIF1A, as contributing to leprosy risk (p = 4.95 × 10-9, odds ratio [OR] = 2.266). We were able to show that affected individuals harboring the risk allele presented with multibacillary leprosy at an earlier age (p = 0.025). We also confirmed the association between missense variant rs3764147 (c.760A>G [p.Ile254Val]) in the GWAS hit LACC1 (formerly C13orf31) and leprosy (p = 6.11 × 10-18, OR = 1.605). By using the population attributable fraction, we have shown that HIF1A and LACC1 are the major genes with missense variants contributing to leprosy risk in our study groups. Consistently, mRNA expression levels of both HIF1A and LACC1 were upregulated in the skin lesions of individuals with leprosy and in Mycobacterium leprae-stimulated cells, indicating an active role of HIF1A and LACC1 in leprosy pathogenesis.

The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China.

BACKGROUND: The pathogen Mycobacterium leprae of leprosy is heavily dependent on the host energy metabolites and nutritional products for survival. Previously we and others have identified associations of several mitochondrion-related genes and mitochondrial DNA (mtDNA) copy number alterations with leprosy and/or its subtype. We hypothesized that genetic variants of mtDNA replication-related genes would affect leprosy. OBJECTIVE: We aimed to identify genetic associations between the mtDNA replication-related genes TFAM, POLG and leprosy. METHODS: Genetic association study was performed in 2898 individuals from two independent sample sets in Yunnan Province, China. We first screened 7 tag SNPs of TFAM and POLG in 527 leprosy cases and 583 controls (Sample I). Expression quantitative trait loci (eQTL) analysis and differential mRNA expression were analyzed to discern potential effect of risk variants. The entire exon region of TFAM and POLG were further analyzed in 798 leprosy cases and 990 controls (Sample II; 4327 East Asians from the ExAC dataset was included as a reference control) by using targeted gene sequencing for fine mapping potentially causal variants. RESULTS: Two tag SNPs of TFAM (rs1049432, P=0.007) and POLG (rs3176238, P=0.006) were associated with multibacillary leprosy (MB) in Sample I and the significance survived correction for multiple comparisons. SNPs rs1937 of TFAM (which was linked with rs1049432) and rs61756401 of POLG were associated with leprosy, whereas no potentially causative coding variants were identified in Sample II. The eQTL analysis showed that rs1049432 was a significant cis eQTL for TFAM in nerve tissue (P=1.20×10-12), and rs3176238 was a significant cis eQTL for POLG in nerve (P=3.90×10-13) and skin tissues (P=2.50×10-11). Consistently, mRNA level of POLG was differentially expressed in leprotic skin lesions. CONCLUSIONS: Genetic variants of TFAM and POLG were associated with leprosy in Han Chinese, presumably by affecting gene expression.

Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China.

Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.

Genetic variants of the MAVS, MITA and MFN2 genes are not associated with leprosy in Han Chinese from Southwest China.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), which has massive genomic decay and dependence on host metabolism. Accumulating evidence showed a crucial role of mitochondria in metabolism and innate immunity. We hypothesized that the mitochondrial-related antimicrobial/antiviral immune genes MAVS (mitochondrial antiviral signaling protein), MITA (mediator of IRF3 activation) and MFN2 (mitofusin 2) would confer a risk to leprosy. In this study, we performed a case-control study to analyze 11 tag and/or non-synonymous SNPs of the MAVS, MITA and MFN2 genes in 527 leprosy patients and 583 healthy individuals, and directly sequenced the three genes in 80 leprosy patients with a family history from Yunnan, Southwest China. We found no association between these SNPs and leprosy (including its subtypes) based on the frequencies of alleles, genotypes and haplotypes between the cases and controls. There was also no enrichment of potential pathogenic variants of the three genes in leprosy patients. Our results suggested that genetic variants of the MAVS, MITA and MFN2 genes might not affect the susceptibility to leprosy.

[Analysis of clinical effects of three operative methods for osteoporotic vertebral compression fracture].

OBJECTIVE: To explore the clinical outcomes of percutaneous vertebroplasty(PVP), percutaneous kyphoplasty(PKP) and percutaneous hollow pedicle screw with lateral holes implanted bone cement reinforcement in treating osteoporotic vertebral compression fracture(OVCF). METHODS: From May 2012 to November 2013, the clinical data of 90 patients with osteoporotic vertebral compression fracture were retrospectively analyzed. According to the different methods of operation, the patients were divided into three groups, including the percutaneous hollow pedicle screw with lateral holes implanted bone cement reinforcement group (group A), percutaneous vertebroplasty group (group B), percutaneous kyphoplasty group (group C), each group had 30 patients. Pre operative, postoperative at 1 day, 3 months, 1 year, the back pain was assessed by visual analogue scale(VAS), and vertebral height compression ratio, Cobb angle were measured by X-rays. RESULTS: All operations were successful and no complications such as postoperative infections and deep vein thrombosis were found. At the final follow up, there were 2 patients with mild postoperative back pain in group A;7 patients with moderate postoperative back pain, 4 patients with severe postoperative back pain, 2 patients with postoperative vertebral refracture in group B; 5 patients with moderate postoperative back pain, 3 patients with severe postoperative back pain, 4 patients with postoperative vertebral refracture in group C. Postoperative VAS, vertebral height compression ratio, Cobb angle of all patients have obviously improved than preoperative(P<0.05). On 1 day, 3 months, 1 year after operation, there was significant difference between group A and group B, C(P<0.05), there was no significant difference between group B and group C(P>0.05). There was no significant difference in group A above items and different times(P>0.05), and there was significant difference in group B, C above items and different times(P<0.05). CONCLUSIONS: The effect of PVP and PKP on the immediately postoperative pain relief was more than percutaneous hollow pedicle screw with lateral holes implanted bone cement reinforcement in treating osteoporotic vertebral compression fracture, but, residual back pain can happen in different extent in the patients underwent PVP and PKP. Percutaneous hollow pedicle screw with lateral holes implanted bone cement reinforcement technique has obvious advantage in recovery of the vertebral height, correction of vertebral deformity, reduction of postoperative back pain.

Narrow-linewidth microwave generation using AlGaInAs/InP microdisk lasers subject to optical injection and optoelectronic feedback.

Narrow-linewidth and low phase noise photonic microwave generation under sideband-injection locking are demonstrated using an 8-µm-radius AlGaInAs/InP microdisk laser subject to optical injection and optoelectronic feedback. Microdisk laser subject to external optical injection at the period-one state provides the microwave subcarrier seed signal, and the optoelectronic feedback serves as direct current modulation to stabilize and lock the generated microwave signal without using the electrical filter. High-quality photonic microwave signals are realized with the 3-dB linewidth of less than 1 kHz and the frequency tunable range from 8.8 to 17 GHz. Single sideband phase noise of -101 dBc/Hz is obtained at a frequency offset of 10 kHz for the generated 14.7 GHz signal. Furthermore, the dependences of photonic microwave signal on the optical injection and optoelectronic feedback parameters are investigated.

Dual-transverse-mode microsquare lasers with tunable wavelength interval.

A dual-transverse-mode microsquare laser with a tunable wavelength interval is designed and realized by using a square-ring-patterned contact window. For a 30-µm-side-length microsquare laser with the square-ring width of 4 µm, the wavelength interval varies from 0.25 to 0.37 nm with the intensity ratio less than 2.5 dB as the injection current increases from 89 to 108 mA. Based on the dual-transverse-mode microsquare laser, the microwave signals with the frequencies of 30.56, 32.70, 35.12, and 39.51 GHz and the 3-dB bandwidths of 47, 53, 54, and 47 MHz are obtained at the injection currents of 90, 95, 100, and 105 mA, respectively.

Four-wavelength microdisk laser array laterally coupled with a bus waveguide.

A four-wavelength microdisk laser array laterally coupled with a bus waveguide is demonstrated numerically and experimentally. The coupled-mode characteristics as well as scattering loss in the bus waveguide caused by the connected microdisks are simulated by a 2D finite-difference time-domain technique. An AlGaInAs/InP microdisk laser array with circular radii of 10.1, 10.2, 10.3, and 10.4 µm is designed and fabricated by common photolithography and an inductively coupled-plasma etching technique. Continuous-wave electrically injected operation is realized at room temperature with the lowest threshold current of 3 mA. Four-wavelength lasing operation is realized with wavelength intervals of 3-4 nm and side mode suppression ratios larger than 25 dB. Finally, the influences of heating effect and thermal cross talk on lasing mode wavelength tuning are investigated experimentally.

Analysis of vertical radiation loss and far-field pattern for microcylinder lasers with an output waveguide.

Vertical radiation loss and far-field pattern are investigated for microcylinder lasers by 3D FDTD simulation and experimentally. The numerical results show that an output waveguide connected to the microcylinder resonator can result in additional vertical radiation loss for high Q coupled modes and affect the far field pattern. The vertical radiation loss can be controlled by adjusting the up cladding layer thickness. Furthermore, two lobes of vertical far-field patterns are observed for a 15-µm-radius microcylinder laser connected with an output waveguide, which confirms the vertical radiation loss.

High-Q modes in defected microcircular resonator confined by metal layer for unidirectional emission.

Defected circular resonators laterally confined by a metal layer with a flat side as an emitting window are numerically investigated based on the boundary element method for realizing unidirectional emission microlasers. The results indicate that Fabry-Pérot (FP) modes become high Q confined modes in the defected circular resonator with a metallic layer. The mode coupling between the FP mode and chaotic-like mode can result in high Q confined mode for unidirectional emission with a narrow far field pattern.

Mitochondrial DNA copy number, but not haplogroup, confers a genetic susceptibility to leprosy in Han Chinese from Southwest China.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number. METHODS: We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis. RESULTS: Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number. CONCLUSIONS: Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.